Podcasts about clinical genetics

Ever thought about why medications work differently for different people? In this episode of Absolute Gene-ius, we explore the exciting field of pharmacogenomics with Wendy Wang, pharmacogenetic laboratory supervisor at Children's Mercy Hospital in Kansas City. Wendy shares how genetics can influence drug metabolism, offering a glimpse into how precision medicine can revolutionize healthcare by tailoring treatments based on an individual's unique genetic makeup.At the heart of Wendy's research is CYP2D6, a cytochrome P450 enzyme responsible for metabolizing around 20% of all prescribed medications. She explains how her lab uses digital PCR to analyze copy number variations (CNV), offering a reliable and precise method to predict drug metabolism. Wendy dives into the complexities of structural variants, the role of digital PCR in enhancing assay efficiency, and why pharmacogenomics is a critical piece of the precision medicine puzzle. Her use of delightful metaphors—like comparing genetic testing to ladling soup—makes complex science both relatable and engaging.In the Career Corner, Wendy opens up about her winding path to molecular biology, which included studying classical antiquity and nearly pursuing a career in history. She emphasizes the importance of resilience in research, embracing failure as a learning opportunity, and encourages budding scientists to reach out to mentors and explore diverse interests. Plus, hear about her most embarrassing lab mishap (hint: it involves a fire alarm) and the proud moment of publishing her first, first-author paper.Visit the Absolute Gene-ius page to learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

An interesting new study from the Geisinger health system in Pennsylvania examining if genomic screening in a large population increases the identification of disease risk prompted Raise the Line to re-release a previous episode about a textbook designed to help all medical providers understand the clinical applications of genomic testing. Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counseling from Elsevier Science Direct dives into the use of this important tool in diagnosis and screening, indicating how individuals may respond to drug therapies, and more. “We really need to educate all healthcare providers about the practice of genetics because they're going to be involved directly or indirectly in genetic testing and conveying information about what the results mean to patients and their families,” explains co-author Dr. Ethylin Wang Jabs, enterprise chair of the Department of Clinical Genomics for Mayo Clinic. Jabs and her co-author, Dr. Antonie Kline, director of Clinical Genetics at the Harvey Institute for Human Genetics at Greater Baltimore Medical Center, chose a format that makes heavy use of case studies to help readers get a better grasp on this complicated field and they also include chapters on direct-to-consumer testing and the ethical and social implications in genomic medicine. “Any kind of potentially predictive testing can have ethical issues related to it, including insurance coverage, testing for family members, protections for minors, and more,” says Dr. Kline. Join host Caleb Furnas for an illuminating episode on an area of discussion in medicine that's growing in importance as the use of genetic testing rapidly increases. Mentioned in this episode: Genomics in the Clinic: A Practical Guide If you like this podcast, please share it on your social channels. You can also subscribe to the series and check out all of our episodes at www.osmosis.org/raisethelinepodcast

In our final episode of the season, we discuss the counselling issues and interventions raised in episode 4: insurance, and have guest input from insurance expert Dr Jane Tiller. Support us by buying a coffee: https://buymeacoffee.com/gcchatpod Sound engineer: Shaun Allen You will find suggestions for support, our privacy statement and disclaimer, and more information about topics referenced in our discussion on our website. https://gcchatpodcast.libsyn.com/  You can find us on Instagram, Facebook and Bluesky. Join the discussion with #GCchatpodcast References mentioned in our discussion: Centre for Genetics Education fact sheet: Life Insurance Products and Genetic Testing in Australia. https://www.genetics.edu.au/SitePages/Life-insurance-products-and-genetic-testing-in-Australia.aspx   Clarke & Wallgren-Pettersson (2019). Ethics in genetic counselling. Journal of  Community Genetics https://doi.org/10.1007/s12687-018-0371-7  The DNA Screen study: https://dnascreen.monash.edu/index.html   Human Genetics Society of Australasia Code of Ethics: https://www.hgsa.org.au/common/Uploaded%20files/pdfs/policies,%20position%20statements%20and%20guidelines/genetic%20counselling/Code%20of%20Ethics%20for%20GC.pdf [original]; https://hgsa.org.au/common/Uploaded%20files/pdfs/policies,%20position%20statements%20and%20guidelines/members%20only%20policies/HGSA%20Code%20of%20Ethics-%20Guideline.pdf [updated] Keenan, et al., (2013). How Do Partners Find out About the Risk of Huntington's Disease in Couple Relationships? Journal of Genetic Counseling https://doi.org/10.1007/s10897-012-9562-2  MacLeod et al., (2013). Editorial Committee and Working Group ‘Genetic Testing Counselling' of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington's disease. Clinical Genetics https://doi.org/10.1111/j.1399-0004.2012.01900.x  Reeder, et al.,(2017). Characterizing Clinical Genetic Counselors' Countertransference Experiences: an Exploratory Study. Journal of Genetic Counseling https://doi.org/10.1007/s10897-016-0063-6 Tiller, et al., (2023). Final Stakeholder Report of the Australian Genetics and Life Insurance Moratorium: Monitoring the Effectiveness and Response (A-GLIMMER) Project. Monash University. https://doi.org/10.26180/23564538.v1  Updates regarding the ban on the use of adverse genetic testing results on life insurance: https://treasury.gov.au/consultation/c2025-626785 ; https://ministers.treasury.gov.au/ministers/stephen-jones-2022/media-releases/total-ban-use-adverse-genetic-testing-results-life

In our penultimate episode of the season, we begin by discussing the counselling issues and interventions raised in episode 3: Opening the envelope. We'll then present this week's case, where the GC faced a difficult situation in predictive test counselling for an adult-onset condition without any treatments.  Support us by buying a coffee: https://buymeacoffee.com/gcchatpod Sound engineer: Shaun Allen You will find suggestions for support, our privacy statement and disclaimer, and more information about topics referenced in our discussion on our website. https://gcchatpodcast.libsyn.com/  You can find us on Instagram, Facebook and Bluesky. Join the discussion with #GCchatpodcast References mentioned in our discussion: Crook et al., (2022). Genetic counseling and testing practices for late-onset neurodegenerative disease: A systematic review. Journal of Neurology. https://doi.org/10.1007/s00415-021-10461-5  Guimarães, et al. (2013). What Counts as Effective Genetic Counselling for Presymptomatic Testing in Late-Onset Disorders? A Study of the Consultand's Perspective. Journal of Genetic Counseling  https://doi.org/10.1007/s10897-012-9561-3  Howard, et al., (2024). Experiences of predictive genetic testing in inherited motor neuron disease: Findings from a qualitative interview study. Journal of Genetic Counseling. https://doi.org/10.1002/jgc4.1904   MacLeod et al., (2013). Editorial Committee and Working Group ‘Genetic Testing Counselling' of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington's disease. Clinical Genetics. https://doi.org/10.1111/j.1399-0004.2012.01900.x Vears, et al., (2020). Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children. Twin Research and Human Genetics. https://doi.org/10.1017/thg.2020.51

At Concierge Medical Associates, we redefine healthcare and longevity medicine by merging traditional expertise with modern innovation. Led by Dr. Murphy, a board-certified concierge physician and specialist with training from Yale and Mount Sinai, our practice stands at the forefront of precision medicine. With over 15 years of experience, Dr. Murphy has been recognized by top media outlets as a Longevity and Regenerative Medicine Specialist as well as a Top Doc for over a decade. He has catered to a diverse clientele, from royalty to elite athletes. Our approach is rooted in personalized care, harnessing the power of genetic insights and AI-driven methodologies to ensure optimal health and longevity for our patients.   By Concierge Medicine Today   January 2025 - Dr. Steven Murphy stands at the forefront of personalized healthcare and longevity medicine, blending traditional medical wisdom with innovative Genetic, Regenerative, Cellular, Orthobiologic, and Energy based insights. As a board-certified specialist in both Internal Medicine and Obesity Medicine, Author, Professor and Executive his expertise is further enriched by his training in Clinical Genetics from renowned institutions like Yale and The Mount Sinai Hospital. With a practice spanning nearly 15 years, Dr. Murphy's clientele is as diverse as it is elite, ranging from royalty to executives to top-tier professional athletes, to everyday individuals looking to live longer and experience a "Life WELL LIVED".   LEARN MORE ABOUT DR. MURPHY ... LEARN MORE ABOUT CONCIERGE MEDICAL ASSOCIATES ...    His commitment to holistic health is evident not just in his practice but also in his outreach efforts. Dr. Murphy hosts the enlightening podcast 'Murphy's Medicine' and co-hosts the thought-provoking 'Hard Truths and Convenient Lies'. His YouTube channel, 'Murphy's Medical Minute', offers bite-sized insights into the latest in health and wellness.   LISTEN TO LATEST INTERVIEW (Jan 2025) with Dr. Murphy and Concierge Medicine Today ...   Beyond his digital presence, Dr. Murphy's expertise has been recognized and featured in prestigious national press outlets, including Bloomberg, USA Today, Newsweek, NY Times, and WSJ. His appearances on television channels such as Bloomberg, ABC, NBC, CBS, and News 12 have further solidified his reputation as a trusted voice in the medical community.   Engage with Dr. Murphy on social media or tune into his podcasts and YouTube channel to embark on a transformative health journey, guided by one of the industry's best.   Dr. Murphy's Authored Books   "Weight Loss Secrets Revealed: Your Ultimate Guide to GLP-1 Medications" (Kindle or Paperback Edition) by Steven A.R. Murphy M.D. "Heal Smarter: 6 Key Questions for Regenerative Medicine Success" by Steven Murphy MD   CONCIERGE MEDICINE TODAY IS THE INDUSTRY'S TRADE PUBLICATION, EST. 2007. DISCLAIMER: THIS SITE DOES NOT CONSTITUTE MEDICAL, FINANCIAL, LEGAL OR OTHER PROFESSIONAL ADVICE. © 2024 CONCIERGE MEDICINE TODAY, LLC. ALL RIGHTS RESERVED. THIS CONTENT/SITE IS NOT WITHOUT ERROR OR OMISSIONS.

We kick off 2025 on Raise the Line by sharing some good news for providers struggling to keep up with the growing number of applications for genomic testing: a new book from Elsevier Science Direct has been designed to arm you with the knowledge you need. Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counselingdives into the use of this important tool in diagnosis and screening, indicating how individuals may respond to drug therapies, and more. “We really need to educate all healthcare providers about the practice of genetics because they're going to be involved directly or indirectly in genetic testing and conveying information about what the results mean to patients and their families,” explains co-author Dr. Ethylin Wang Jabs, enterprise chair of the Department of Clinical Genomics for Mayo Clinic. Jabs and her co-author, Dr. Antonie Kline, director of Clinical Genetics at the Harvey Institute for Human Genetics at Greater Baltimore Medical Center, chose a format that makes heavy use of case studies to help readers get a better grasp on this complicated field and they also include chapters on direct-to-consumer testing and the ethical and social implications in genomic medicine. “Any kind of potentially predictive testing can have ethical issues related to it, including insurance coverage, testing for family members, protections for minors, and more,” says Dr. Kline. Join host Caleb Furnas for an illuminating episode on an area of discussion in medicine that's growing in importance as the use of genetic testing rapidly increases.Mentioned in this episode: Genomics in the Clinic: A Practical Guide

JCO PO author Dr. Michael J. Hall, Professor of Medicine, Chairman of the Department of Clinical Genetics, and Co-Leader of the Cancer Prevention and Control Program at Fox Chase Cancer Center in Philadelphia, PA, shares insights into the JCO PO article, “Uptake of aspirin chemoprevention in patients with Lynch Syndrome.” Host Dr. Rafeh Naqash and Dr. Hall discuss the finding that only about 1 in 3 patients with Lynch Syndrome use aspirin for cancer chemoprevention. TRANSCRIPT  Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash podcast editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, I'm excited to be joined by Dr. Michael J. Hall, Professor of Medicine, Chairman of the Department of Clinical Genetics and co-leader of the Cancer Prevention and Control Program at the Fox Chase Cancer Center in Philadelphia, and also the lead author of the JCO Precision Oncology article entitled, “Uptake of Aspirin Chemo Prevention in Patients with Lynch Syndrome.” At the time of this recording, our guest disclosures will be linked in the transcript. Dr. Hall, welcome to the podcast and thank you for joining us today to explain and help the listeners understand your interesting research that was just published in JCO Precision Oncology. Dr. Michael J. Hall: Thank you so much for having me and really thanks for the interest in our work. I think it's an important subject and I hope people will also find it as interesting as we do. Dr. Rafeh Naqash: Absolutely. I think your research touches upon a few things. One, obviously, touches upon Lynch syndrome germline assessments of individuals. It also touches upon chemo prevention, prevention in general, and it also touches upon the knowledge and understanding of chemo prevention aspects. So to start off, I would like to ask you, for the sake of our listeners, many of whom who may not necessarily fully understand the length and breadth of Lynch syndrome, maybe perhaps some residents or trainees out there, could you tell us what Lynch syndrome is, what some of the mutations are, what the implications are, and then we can try to go and delve more into the research topic. Dr. Michael J. Hall: Sure, I'd be happy to. Lynch syndrome is probably, in the hereditary cancer genetics world, one of the most common hereditary risk syndromes we encounter. Recent estimates are that probably roughly about 1 in every 280 individuals in the population is a carrier of a pathogenic variant, one of the Lynch syndrome genes, there are roughly four. There's sort of a fifth gene that is also involved with Lynch syndrome, but really, we largely think about four genes in Lynch syndrome, MLH1, MSH2, MSH6, and PMS2. Over time we've begun to learn, and I'll say that the guidelines that we develop have become more specialized for each of those genes. They are not sort of all the same in the cancers they cause and the way they behave. But roughly, what is Lynch syndrome? It's a syndrome of DNA mismatch repair. So, individuals who have Lynch syndrome have some degree of deficiency in their ability to repair DNA via the mismatch repair system. Depending on the pathogenic variant that is within a family, that may be related to a more severe deficiency of mismatch repair, repair, editing, or for instance, with the PMS2 gene, we've learned over time that actually the degree of DNA repair deficiency is actually a milder phenotype. These individuals over a lifetime are at risk of a variety of different kinds of cancers, the most common being colon cancer. And the risk of that is variable by gene. With MLH1 and MSH2, it's close to 50% over a lifetime. With MSH6 and PMS2, somewhat lower. There are also risks of endometrial cancer, gastric cancer, ovarian cancer, pancreas cancer, a number of other ones. But they're all related again to the same underlying molecular deficiency, and that's this deficiency of being able to repair mistakes made in the DNA accurately. And so, mutations accumulate in the genome of cells in various tissues of the body. Dr. Rafeh Naqash: Thank you for that very simplified version of a very complicated topic otherwise. So, as you mentioned, these different genes have different implications. Perhaps some have higher risks for colorectal cancer than others. What are some of the current standardized approaches for screening or following these individuals over the course of their journey until perhaps either get detected with cancer or while they're being monitored? Dr. Michael J. Hall: Sure. It's a great question, because this is very much a moving target in this disease. I'm going to give you a quick second of history that up until maybe about six or seven years ago, we had uniform guidelines, really, that any Lynch syndrome pathogenic variant carrier should start colorectal cancer screening. Usually, we were recommending between the age of 20 and 25, and this was usually annual colonoscopy. And for years that was the standard. In more recent years, we've stuck to that tight interval, particularly in the higher risk genes, MLH1 and MSH2, although the guideline now reads every one to two years, because we recognize people need some degree of flexibility to live their lives. And there are people in the population who are more risk averse, and there are those who want a colonoscopy every year because they want to stick to that schedule. For MSH6, we recommend a somewhat later start at age 30, and that can be every one to three years for colon screening and for PMS2, similar recommendations, although I think there is a chance in the coming years, we may actually expand the screening interval even more, again, because the risks are somewhat lower. We still have ways to go in terms of screening for the other cancers in Lynch syndrome. I'll say that, for instance, endometrial cancer, which is the second most common cancer in this disease, we still struggle with what is the best way to screen women for a risk of endometrial cancer. Our guidelines in the past were always somewhat draconian, that once women sort of finish childbearing, they should immediately have a total abdominal hysterectomy and oophorectomy. And I'll say that with greater input from the gynecologic and GYN ONC community, we have somewhat softened those recommendations, especially for the endometrial cancer and also the age at oophorectomy, because we recognize that there were compensatory risks of taking the ovaries out too early in some women, risks of bone loss and cardiovascular disease. So those are the most common. For other tumors in Lynch syndrome, for instance, gastric cancer and pancreas cancer, the guidelines are still really evolving, and different groups have put out guidance for clinicians. And I'll say NCCN, which I participate in and help write those guidelines, has very good recommendations for docs. But I'll say that it is again, back to the idea that it's a moving target. And as we learn more, hopefully, we'll have better recommendations. Dr. Rafeh Naqash: I completely agree as far as a moving target is concerned, and we often look at the disconnect between the recommendations and then what's implemented or followed in the real-world setting. So I have a question in that context, and my question is, when you identify these individuals with Lynch syndrome, perhaps let's talk about academic settings, and then we can try to delve into how this might work in the real world community oncology settings, where the real world population actually exists, 60, 70% of individuals get treated in the community. So, when you talk about an academic center, what is the flow of the individual? Does the individual stay within the geneticist when they're diagnosed? Does the individual go to the primary care and the geneticist makes the recommendation and the primary care follows the recommendation? How does it work for you and what are some of the models that you've seen work best perhaps at different academic centers? Dr. Michael J. Hall: I think you get at a really great question. And I'll say there is really no one model. And I think models have to be fluid these days because people with Lynch syndrome are really being identified in more and more diverse settings, and by diverse means. I'll say at my own center, we are more of a traditional practice. So, we do the pre-test and the post-test counseling. Once we have counseled individuals identified Lynch syndrome, we will usually make referrals. If folks don't have a gastroenterologist that they have interacted with before, we keep them in our own group and follow them. But their Lynch syndrome home really sits both in a continuity clinic that I run for patients to come back and circle around every one to two years just to review guidelines and review their screening results. However, I do really make an effort to, first of all, keep primary care docs involved, because I think some of the things we recommend, it is critical that the primary care doc is aware so that patients are keeping up with some of the recommendations. For instance, we often recommend skin screening to make sure that folks have had at least one good skin exam somewhere in the 40s. And I think the primary care doc can be very helpful in making sure that happens. It is somewhat different, I think, in the community where many more patients with Lynch syndrome are being identified these days. I suspect that much more of the burden of making sure Lynch syndrome patients are well hooked in with a gastroenterologist and with a dermatologist and maybe a urologist probably does fall on that primary care doctor. In my experience, some primary care physicians have really kind of jumped up in and taken hold of this and really know their Lynch syndrome well, and I think that's amazing. I do, however, as kind of an expert in this area, I do get a lot of referrals in from the community as well, from docs who just feel that they may not have quite that expertise that they can get at a comprehensive center. So, someone may come in to me just for a consult to review what my recommendations would be, hear about research, hear about what's going on in the field, and those folks will often touch base with me again every couple year or so. Often, another thing I've started to experience is that I may meet people once or twice early on in their diagnosis, and then they go back to their primary docs and I may not hear from them again until something more profound happens in the family or into the patient and they get their screening colonoscopy and a stage 1 cancer is found. Often then, that's the patient who, after four or five years, will contact me again and say, “We haven't talked in a while, but something has happened, and can we re-consult about what would be the best way to do things?” Dr. Rafeh Naqash: Again, like you said, lots of moving targets, moving aspects to this whole care of these individuals. Do you think, in your experience, nurse navigation, maybe some centers have already implemented that perhaps you might have that, do you think nurse navigation could play a certain level of role? You know how in the multidiscipline care we have nurse navigators that coordinate care between radiation oncologists, medical oncologists, thoracic surgeons. So that's something that is being implemented. My second part of that question is telehealth in this case, maybe it's a little more difficult for somebody to drive three hours to come to you for a visit just to check in versus maybe virtually talking to you or your team getting a sense of where things are at in terms of their screening and their follow ups. Dr. Michael J. Hall: I think both are great, great questions and absolutely, we use both of those pieces in our model. And I know from colleagues that they do as well. So, in terms of navigation, we do have an embedded nurse navigator within our department. She joins and kind of helps facilitate all of our high risk follow up clinics. Mine, for GI, we have a high-risk prostate clinic, we have several high-risk breast clinics and those are populated by providers. We have a couple of nurse practitioners in my genetics group and a PA they are sort of the main provider in those clinics, but they are very much supported by that nurse navigator who, as you well point out, really helps with the coordination of the care. Telehealth as well, I do 100% support because you're absolutely right, if you look at a map of the United States and you first of all look at where there are good counseling services available, of course, there's ample counseling in the major metropolitan areas all over the U.S., but the minute you get outside of those counseling and then other management expertise, then– So we do have a model where particularly for folks who are from central Pennsylvania and sometimes more towards western Pennsylvania, I do have some individuals who've been identified with Lynch syndrome who telehealth in, again, for that follow up. A sort of side notes on telehealth, I think we learned a lot from the pandemic about how to use telehealth more effectively. And thank goodness, we've all gotten up to speed in medicine of how to be better telehealth providers. Unfortunately, I feel like with the pandemic kind of waning, there's been a little bit of a regression of the telehealth laws. So now if I want to do telehealth with someone who is from New Jersey, even though New Jersey sits very close to where I practice, it's more complicated now. Again, I have to get a license and same thing with New York and same thing with Delaware. I sort of wish we had a little bit of a better and welcoming system in the states where you could have easier ability to practice, especially when states were quite close using telehealth. But nonetheless, that's for another podcast, I think. Dr. Rafeh Naqash: Well, thank you again for some of those interesting aspects to this whole topic. But let's dive into the thing that we are here to talk about, which is aspirin in these individuals. So can you give us some context of why aspirin, what's the biology there and what's the data there, and then talk about why you did what you did. Dr. Michael J. Hall: So, we've known for many years that aspirin has preventive properties in terms of preventing colorectal cancer. Many observational studies and some interventional studies have shown us that aspirin has benefits for reducing the risk of colon cancer in an average risk population. There was even an interventional trial a number of years ago that looked at individuals who made polyps, and this looked at particularly adenomas, which we know are the precancerous polyps and adenoma prevention using aspirin. And that study clearly showed that aspirin had benefits for lowering risk of recurrent polyps and adenomas. Particularly even a lower dose of aspirin, 81 milligrams, was effective in that setting. Aspirin's also been studied in other hereditary risk syndromes, the most visible one being FAP, where data have shown that aspirin does help reduce polyp count in FAP, although is certainly not a perfect chemo prevention for that disease. So, in that background of knowing that aspirin has many benefits for colorectal cancer prevention, a study was initiated in the UK a number of years ago called the CAPP2 study, with its lead investigator being John Burn. And in this study, it was a two-arm factorial study that was not just aspirin, but they were also looking at resistant starch, which there was a lot of excitement about resistant starch back then. But in this study, they looked at using aspirin as a way of lowering risk of colorectal cancer in patients with Lynch syndrome. And that study, which was initially reported in The New England Journal, the initial outcomes did not actually show benefits in its first analyses of adenoma risk and colon cancer risk. But what they found over time was that there was a delayed effect and, in a follow, up paper looking at 10 plus years of follow up, they showed a substantial reduction in risk of colon cancer, about 40% risk reduction, which was really striking and exciting in the field to see such a large benefit from aspirin. Now, one caveat was in the analyses they performed, it was those individuals who were able to stick to the aspirin dose in that study, which was 600 milligrams a day. I always say to folks that back in the day, that was not a lot of aspirin, although I think these days we're much more skeptical about taking larger doses of any drug. So, 600 milligrams is roughly about two adult aspirin in the U.S. So those folks who were able to stick to that dose for at least two years were the ones who gained benefit from being on aspirin. And what was interesting is that benefit endured for really 10 years after those two years of being able to take aspirin. So, this was striking and it really changed our thinking about whether there may be chemo prevention options for folks with Lynch syndrome. However, and I think what formed the background of our study here was that there was a somewhat equivocal endorsement of aspirin by the major guidelines committees, mainly because, as we all know in oncology, we love one first big study, but we always really love secondary studies that solidify the finding of the first study. And so, because this was such a niche group and no one else out there was doing big aspirin studies when this result came out in 2011, we've sort of been waiting for many years for some follow up data. And the NCCN guidelines have always been a little bit equivocal that people could consider using aspirin to lower risk in their patients with Lynch syndrome, but without that kind of strong, “Everyone should do this.” And so, this has kind of formed the background of why we performed the study that we did. Dr. Rafeh Naqash: Interesting. And then you had a bunch of observations. One of the most important ones being that use of aspirin was pretty low. Could you dive into that and help us understand what were some of the factors surrounding those low implementation aspects? Dr. Michael J. Hall: Of course. So, what we were interested in then again in that background was, here's a high-risk population, docs are getting somewhat maybe ambiguous information from the guidelines, but what actually is going on out there in practice? How many patients are actually using aspirin? What doses are they using, and what are some of the factors that drive it? So, we performed a survey that actually occurred in two parts. One started at Fox Chase in our population here, and then we expanded it online to a convenience sample. Overall, we had 296 respondents. And yeah, what we found actually was the uptake of aspirin was only about roughly 30%, 35% or so among patients who were eligible to take aspirin. When you actually drill down to those people actually taking aspirin because they wanted to prevent Lynch syndrome, it was even lower. It was in the range of 25% to 30%. This somewhat surprised us. And then when we looked at the doses that people were using, of course, thinking back to that 600-milligram dose that was tested in the study, we found actually that more than half of folks were taking low dose aspirin, like an 81 milligram, and only about 8% of our study participants were using that 600-milligram range. So, again, I would say this somewhat surprised us because we thought it might be higher than this. I'll say as a somewhat caveat to this though, is that back to my comment about we always like another study that confirms our findings, and at a meeting earlier this year, there was a study performed in a New Zealand population by a medical oncologist named Rebecca Tuckey. And she actually found almost the same identical results that we did in the New Zealand population - very, very similar uptake rates of aspirin in the New Zealand population with Lynch syndrome, so kind of confirming that something we've stumbled upon appears to be true. But how do we understand why some folks use aspirin and why others don't in this condition? Dr. Rafeh Naqash: You had a very robust question there from what I saw in the paper. And some of the questions that I had around that was, did you or were you able to account for demographics, education level of the individuals? Were you also able to assess whether these individuals felt that they had been counseled appropriately when they met with either a primary care physician or of any provider on the genetic side, physician or non-physician? So how did you get an assessment of whether it was an apples-to-apples comparison or were there a lot of confounders. Dr. Michael J. Hall: Very good question. And of course, in the setting, unfortunately, we weren't interviewing people, which we could have gotten much richer data in some ways. And there were other things we were looking at in this survey as well, so our aspirin questions, we had a number of them, but perhaps in retrospect, it would have been nice to even have more. We did have some common covariates, age, sex, ancestry, marital status, which gene was affected, whether they had a history of cancer. We did not have education, unfortunately. And I think your question is a great one, but we did not actually ask folks about whether they had been counseled by their provider or their genetic counselor or someone else about whether they should use aspirin or not. We simply wanted to see whether folks were using it. We did ask them again whether they were using it because they wanted to lower their risk of a Lynch syndrome cancer or whether they were using it for another reason or a combination of both. So, yes, in retrospect, we actually do have another study plan to kind of drill deeper into these questions of is it more of a hesitancy question? Is it more of a question of just not as much awareness? Are there other reasons? I think there's a lot to answer, and I think answering these questions is really important because we both want to make sure we're talking about interventions that we think can help people, but we need to understand also some of the barriers they may face. And if people do have barriers to some forms of chemo prevention or I think about some of the vaccine research that's going on right now, if the kinds of things that we're working on to develop are actually not going to be palatable to the patient, the population, then I think we kind of need to step back and say we need to maybe understand what people want so that we can have a good meeting of what's going to work and what's going to fit the needs and lifestyles of our patients. Because these are things they might have to do for many, many years and starting maybe even in their 20s or 30s. So, it makes a difference. Dr. Rafeh Naqash: From what you learned in the study, are you thinking of any subsequent interventional approaches, whether they involve a simple phone call to the patient regularly or perhaps, even though I'm not a big fan of EMR prompts, like an EMR prompt of some sort, where they talk, where they're instructing the provider, whoever is seeing the patient physician or the APP or the geneticist that, “Hey. Did you counsel the patient?” And its sort of a metric how in the oncology side they say, “Well, your metric is you should stage all patients and you should talk about toxicities from a reimbursement standpoint and also from a quality improvement metric standpoint. “Is that something you're thinking of? Dr. Michael J. Hall: 100%. So, when we looked at the barriers, many of the kind of the things that were the strongest predictors of who used aspirin versus who didn't were really patients' perceptions of whether aspirin would cause side effects or whether aspirin would be burdensome to take on a daily basis, also, just how much benefit they thought would come from taking aspirin. So, I think there's, number one, I think an intervention and our next delve into this as an interventional study would be both education about the delta prevention benefit that you get from aspirin, the safety profile of aspirin, which is really quite excellent. And also, I think the data that are so important that in this study by Burn et al, it was actually only two years of intervention that then paid off for 10 years down the line, right? So, I think that's important. The other thing that we actually learned as an aside in this study was actually the kind of intervention that patients wanted the most was actually not a drug and was not a vaccine and was not another kind of special scope to stick somewhere. What they actually were most interested in were interventions related to diet. People really see diet as being an important part of health, or I should say diet and nutrition. And so, I think a subsequent study would perhaps wed both a nutritional intervention of some kind with a chemo prevention in some sort of time limited fashion, so that folks felt like they were both focusing on something that was more important to them, but also, something that was related to the study that we wanted to look at. So that's kind of my idea of where we're going to go in the future with this. Dr. Rafeh Naqash: Excellent. Sounds like the next big RO1 for your group. Dr. Michael J. Hall: Let's hope so. Dr. Rafeh Naqash: Well, I hope the listeners enjoyed talking about the science and learning about aspirin Lynch syndrome. The last couple of minutes are about you as an individual, as an investigator. Can you tell us what your career journey has been like, how you ended up doing what you're doing, and perhaps some advice for early career junior investigators on what this whole space looks like and how you pace yourself and how they can learn from you? Dr. Michael J. Hall: I really got interested in oncology during my residency training. I really found that I really liked oncologists. I found them to be a bit more of a science focused group. They liked research, but you're in oncology because you understand the fears and the challenges of cancer. And so, it's both a combination of that love of science, but also that real human touch of taking care of people. The thing I always tell my fellows as well is the other thing I love about oncology is if you tell people they don't have cancer, they don't want to come back to you. Now, of course, that's modified in the prevention setting. But I really like that when people come to me in my GI oncology clinic, it's because they have a diagnosis and if I say you actually don't have cancer, they go off to their life, and so you're really spending your time on real subjects. The person who really got me most interested in Lynch syndrome and this kind of prevention research was a mentor from University of Chicago, Funmi Olopade, who really has been an enormous mentor for many, many people in the field. Actually, three people in my fellowship class all went on to careers related to genetics and genomics. So, she's been highly influential and continues to mentor me even in my mid-career. I think in terms of pearls or what keeps this interesting for me, I think as much as oncology treatment and new drugs and trials is super exciting, I love being able to step away from that into my genetics and prevention population and kind of focus on treating people in a different format. Patients who are healthy but are worried about cancer because of a family history or carrying a gene or otherwise, and I feel that that's where I can have also an important impact, but on a different level in educating people and helping them understand how genetics works in an understandable and simple way, but also giving them some tools. And one reason for this study, and the reason I study preferences related to prevention is, again, I don't want to just develop something and spend 10, 15 years of my life developing some intervention that everyone looks at and is like, “I don't really want to do that.” I want to really understand what it is that is important to the patients so that we can hopefully work together to develop things that can not only have impact but have impact on a wide scale. Dr. Rafeh Naqash: Awesome. You mentioned Dr. Olopade. I crossed paths with her actually at an international medical graduate community of practice session earlier this year at ASCO where she talked about her journey as an immigrant, talked about how she started, the kind of impact that she's had. It was obvious evident in the picture that she showed with all her mentees who have kind of gone all over the world. So that was very phenomenal. And it's surprising how small of a world we live in. Everybody knows everybody else. Dr. Michael J. Hall: It's crazy. More so than anyone I think I've met in my career; she is really a huge believer in mentorship and spending that extra time with your mentees. And she has been someone who has continued to promote me as an investigator and build me up and get me involved in things. And like I said, I've been in oncology now for quite a few years. But having that person who I think is always thinking about their trainees and people who have learned and grown under them, because what it does is it gives you that fire as well as an investigator to do the same thing for the people that you are a mentor for and train. So, I try to be just as good of a mentor to my genetic counselors and the fellows who come through me and my APPs to give them opportunities to get them excited about research and when they have these big moments to do that. So, yeah, I know Funmi just has had a huge impact on the field of genetics. I still remember some of our early conversations on the wards when she said to me, “Oh, this is such an interesting case. We don't really have anyone who's studying Lynch syndrome so much right now and you should really get into this area.” And I remember thinking, “Okay, I want to develop a niche and here's a niche that's waiting.” Dr. Rafeh Naqash: Clearly it paid off big time and you're paying it forward with your mentees. So, thank you again for joining us. This was an absolute pleasure. Hopefully, the listeners learned a lot about the science and also your journey and how you're trying to impact the field. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinion, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.      

First cousins, second cousins, fourth cousins three times removed... What's the difference? And if all three billion letters of your genetic code were unique, how distant a relation would you have to have before the two of you didn't share any of these original letters anymore? This scenario has some assumptions, but we'll use it to explore how large the human genome is! Sources for this episode: Berger, B. M. (1960), How Long Is a Generation? The British Journal of Sociology 11(1): 10-23. Bistritzer, T., Fried, K., Lahat, E., Dvir, M. and Goldberg, M. (1993), Congenital contractual arachnodactyly in two double second cousins: possible homozygosity. Clinical Genetics 44: 15-19. (for second cousins, nothing except abstract) Matsamura, S. and Forster, P. (2008), Generation time and effective population size in Polar Eskimos. Proceedings of the Royal Society B: Biological Sciences 275: 1501-1508. McDermott, M., Genealogy Explained (2022, updated 2024), What are Double First Cousins (online) (Accessed 24/04/2024). Skipper, M. (2012), User's guide to the human genome. Nature Reviews Genetics 13: 678. Author unknown, Ancestry (date unknown), What is a second, third, or fourth cousin- or a cousin once removed? (online) (Accessed 24/04/2024). Author unknown, Wikipedia (date unknown), Family tree of English monarchs (online) (Accessed 24/04/2024). Author unknown, Wikipedia (date unknown), Family tree of the British royal family (online) (Accessed 24/04/2024). Author unknown, 23 and Me (date unknown), Average Percent DNA Shared Between Relatives (online) (Accessed 24/04/2024).

As we continue our Year of the Zebra focus on rare disorders, we're going to focus on the productive relationships that can develop between the families of children with rare diseases and the researchers who are trying to develop treatments and cures.  Join Raise the Line host Lindsey Smith as she explores the various dimensions involved with Jennifer Wells, whose young son has a neurodevelopmental syndrome called CAGS (Chopra Amiel Gordon Syndrome) and her son's physician, Dr. Maya Chopra, a clinical geneticist who co-discovered the gene in question and who is leading an international study on CAGS. “It's so important as researchers that we engage and include families in our research design and methodology so we understand what are the most relevant and meaningful endpoints that we're going to use for trials,” explains Dr. Chopra, director of Translational Genomic Medicine at the Rosamund Stone Zander Translational Neuroscience Center at Boston Children's Hospital. In turn, family members can be a critical connection to the tightly-knit communities that grow up around specific disorders which are eager for the latest information. “As materials become available from Dr. Chopra and her research team, then I try to partner with them to get it out to the community and have those resources available,” says Jenifer. Tune in to this fascinating discussion to learn about other benefits of these relationships, what's happening in CAGS research, and an approach to research being pursued by Dr. Chopra that will help make small studies more scalable, potentially benefitting multiple conditions at once. Mentioned in this episode:Rosamund Stone Zander Translational Neuroscience Center

In this episode Liz and Jesse are joined by Dr Chirag Patel. Chirag is a consultant clinical geneticist at RBWH. We learned a lot about the world of clinical genetics right now and what is on the near horizon. Chirag's Five Things: Genetics 101. Complex vs pure genetic conditions. What is clinical genetics? Genetic testing. Psychosocial and ethical considerations of clinical genetics.

JCO PO author Dr. Alicia Latham shares insights into her JCO PO article, “Prevalence and Clinical Implications of Mismatch Repair-Proficient Colorectal Cancer in Patients With Lynch Syndrome.” Host Dr. Rafeh Naqash and Dr. Latham discuss microsatellite instability-high status as well as familial risk and testing. Click here to read the article! TRANSCRIPT Dr. Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Social Media Editor for JCO Precision Oncology, and Assistant Professor at the OU Stephenson Cancer Center.  Today we are excited to be joined by Dr. Alicia Latham, Medical Director at the Memorial Sloan Kettering-CATCH, and the Assistant Attending Physician, General Internal Medicine and Clinical Genetics. Dr. Latham is also the author for our JCO Precision article titled "Prevalence and Clinical Implications of Mismatch Repair-Proficient Colorectal Cancer in Patients With Lynch Syndrome."  At the time of this recording, our guest on this podcast had no disclosures.  Dr. Latham, thank you so much for joining us today, and welcome to our podcast. Dr. Alicia Latham: Very happy to be here today. Thank you for inviting me. Dr. Rafeh Naqash: For the sake of this podcast, we'll refer to each other using our first names if that's okay with you. Dr. Alicia Latham: Sure. Dr. Rafeh Naqash: So this is a very interesting, broad topic that I wanted to discuss with you, and hopefully, our listeners find it very interesting. It touches on a broad range of currently relevant precision medicine-related topics, which is mismatch repair deficiencies, colorectal cancers, and Lynch syndrome. Could you try to give us an understanding of what we know so far about colorectal cancers that are mismatched repair deficient as well as Lynch syndrome, which would be, hopefully, an interesting segue into your article? Dr. Alicia Latham: Sure. In general, I think when speaking of mismatch repair deficiency in the setting of colorectal cancer, we know that the vast majority of the time it's somatically driven, not necessarily that there was an inherent genetic predisposition that drove it, and we've known that for quite some time. But the issue is that there's still about 15% of the time or so when you're looking at colon cancers, that a germline component is probably driving that mismatch repair deficiency, i.e. Lynch syndrome. And that became exceptionally relevant whenever universal screening for said tumors was occurring as a way to screen for Lynch syndrome. And even perhaps more importantly, with the usage and increasing usage of immune checkpoint blockade because we know that those cancers respond exquisitely well because of that driver. And in terms of our understanding, typically because patients with Lynch syndrome inherently have a defect in mismatch repair, their tumors, pan-cancer, which we published on previously in JCO, demonstrate mismatch repair deficiency or MSI high status, if that was contributed.  So really the point of looking at this was to take that initial work and kind of turn it on the flip side. And rather than assessing all tumors for MMRD status or MSI high status, to look at colorectal cancer tumors at our institution, find the underlying prevalence of Lynch syndrome, and then see how many presented with a mismatch repair proficient tumor and what that may or may not imply or mean for the patient clinically. That was really the whole point. Dr. Rafeh Naqash: Excellent, thank you so much for the explanation. Now, I do remember when I was a fellow in my first-year fellowship, I would often get confused, and I think NGS was just becoming the thing of the day a couple of years back, especially for metastatic tumors. I would often get confused between MMR deficiency and MSI high. And for trainees who are going to start in a week or so into their fellowships, who hopefully will be listening to this, could you give us a simpler version of how you would explain to a new trainee what MMR deficiency versus MSI high is? Dr. Alicia Latham: Sure. So we'll start with MMR deficiency. So IHC or immunohistochemical analysis has been around for a while. That's kind of your classic way of assessing for this. And really what that means is that when the tumor is stained for the mismatch repair proteins, they're found to be deficient, meaning that one or more of said proteins is not expressed in the tumor. So that's mismatch repair deficiency. Usually, the staining patterns have a very unique pattern to them, meaning that you'll typically see MLH1 and PMS2 absence go together, or MSH6 and MSH2 absence go together. They go hand in hand. I call it the “buddy system.”  Microsatellite instability - before defining what that means, I think it's important to explain what microsatellites themselves are. And so when I talk to trainees, I say microsatellites are just little repeat sequences throughout our genome that are kind of little “bookmarks.” And our mismatch repair system finds those little repeat sequences to try to look for errors, spelling errors. That's the spell checker of the mismatch repair. And so it scans, finds a bookmark, reads to see if there's a mismatch. If there is, it corrects it and then goes to the next one, and so on and so forth.  Over time, if those mismatches aren't repaired, then you may see a discrepancy in the now cancerous tissue versus the normal. And that is what's called microsatellite instability, meaning that the tumor, the variance in those repeat sequences is different in the tumor versus the normal tissue. They typically have a concordance rate of greater than 90%. Dr. Rafeh Naqash: So basically, in your practice, do you often do, and I know you've touched upon some of the overlapping incidences in your paper, but do you, in your practice, do MSI testing using NGS and IHC testing on all patients that need to be tested? Dr. Alicia Latham: So it depends on how they get to us. By the time patients have gotten to genetics, usually at MSK because we have this institutional protocol, MSK-IMPACT, these patients are offered paired NGS sequencing, so tumor-normal sequencing, and they can either consent to just somatic profiling, or somatic and germline. And so by the time we see them, our NGS profile uses MSIsensor for categorization of the MSI status. So they usually have that.  But if there's any discordance or surprising feature, say the patient comes in, their tumor is MSS but the patient has a known MLH1 germline mutation and the family history looks striking for Lynch syndrome, that's suspicious. So we'll do an orthogonal method to look at the tumor, usually starting with IHC to see if it's mismatch repair deficient because that's very easy to do. And then we can also have an additional analysis that's in the process of going through clinical validation called MiMSI, which is essentially an algorithm that has been trained as a machine learning tool on the original impact data and MSIsensor that has a higher clinical validity in tumors that have low tumor content. So MSIsensor is known to have a bit of a flaw in that in tumors with less than 10% of tumor content in the sample, that it may be artificially low. So that's why we also look at that too. So we typically do, if we're suspicious, we'll do an additional method. Dr. Rafeh Naqash: Interesting. Now, going to this interesting work that you published in JCO PO, it seems the premise is more or less around understanding what percentage of patients with Lynch syndrome have mismatch repair proficient colorectal cancers that could be driven by other sporadic changes, genomic changes, or whatever factors that could be, perhaps, leading to tumorigenesis. So was that how you started this project? Or were you trying to answer a different question but understood that this could be a very clinically relevant or meaningful question also? Dr. Alicia Latham: Honestly, how this came about was we had our first patient come in with- had known Lynch Syndrome and had a proficient tumor. And what brought up the question about it as to why it was clinically relevant is one, they were considering immunotherapy, and the oncologist was like, “Do I or do I not do this?” And then the second question is: well, what does this necessarily mean for the family? If this tumor is truly mismatch repair proficient, does that mean that the Lynch syndrome caused it, and so, therefore, someone that tests negative, or deficient, someone who tested negative for the Lynch syndrome, may be off the hook for screening? Or if it's truly proficient, does that family member now have a familial risk for colon cancer and should perhaps consider increased screening? So those were the clinical questions that came up in that case.  And because of that case, that was like, well, how many times does this really happen? Has anybody published on this yet? And we didn't see anything at the time, and we had this large impact data cohort. So we decided to dive a little bit deeper and see what we can find. It is rare, but it happens. Dr. Rafeh Naqash: You bring this very interesting point that some of the very clinically relevant projects or research, it stems from a unique clinical patient scenario where you saw an individual, you tried to understand why, and you took it to the next step. In fact, I do drug development, Phase 1 clinical trials, and I have an individual with a history of Lynch syndrome and germline positive with osteosarcoma but mismatch repair proficient. And before reading this paper, I've come across some other data. In the Phase I setting when you don't have a target, your next best option is to go for immunotherapy--novel immunotherapy-based approaches. And in this individual, I was debating whether an immunotherapy approach would be reasonable or not. But based on the data and then looking at your paper, I am less convinced that with a mismatch repair proficient tumor, because in the standard care setting, obviously, immune checkpoint inhibitors have an indication for tumor MSI high, not germline. So these are rare, but when they happen, it does bring into question, like you said, implications for the family, whether or not immunotherapy is a relevant option in those individuals. So, very, very important to understand this.  So could you tell me, and the listeners also, walk us through the data set that you looked at? What was the denominator and how did you end up with the sample size that helped you understand this topic? Dr. Alicia Latham: Sure. So we first started with just looking at our overall MSK IMPACT cohort at the time that had undergone germline or analysis of their DNA. And so that was over, at the time, 17,000 cases. Then looking at those, we wanted to understand and assess the underlying Lynch syndrome prevalence of all of those cases. So overall, it was 17,617 pan-cancer patients. And we found, of those, about a 1.5% prevalence of Lynch syndrome pan-cancer. And then of those we assessed, of those patients with known Lynch syndrome, how many had at least one colorectal tumor that underwent that NGS profiling, and that came out to about 36% or 86 cases.  Of course, because Lynch syndrome is known to have synchronous and metachronous tumors, there were a few patients that had more than one colorectal cancer assessed, so it actually ended up being 99 pooled tumors. So then you're looking at 99 pooled tumors there of those Lynch syndrome cohorts, of which about roughly 10% were found to be mismatch repair proficient, and they were also MSS or microsatellite stable by MSIsensor. So that was how we broke it down. Dr. Rafeh Naqash: Interesting. Now, looking through your manuscript, I understood that you identified some unique differences between the mismatch repair proficient Lynch syndrome-positive individuals and mismatch repair deficient individuals in the cohort. What were some of the highlights of the different clinical characteristics that could be clinically meaningful? Dr. Alicia Latham: Sure. So I think one of the most important things, at least from a genetics perspective, was we did find an enrichment among the mismatch repair proficient group of those having either an MSH6 or PMS2 germline variant. And that's notable because those are known to be kind of our lower-risk genes. And in fact, oftentimes patients and families don't meet typical clinical criteria for genetic testing in those families. So PMS2 is probably the most obvious case of that where the families don't really look suggestive of classic Lynch syndrome. That was significant even in a small cohort, so it was 89% of patients with mismatch repair proficient tumors had MSH6 or PMS2 mutations.  The other, while it didn't quite achieve statistical significance simply because it was a small cohort, the age of onset was different. So mismatch repair proficient, they were a little bit older. Our median age of onset was 58 in that group and then the mismatch repair deficient group median age was 43%. So I think if we had a larger sample size that would achieve statistical significance there.  The other important caveat was just kind of when they presented, what stage did they present at. So, unfortunately, we did see a higher prevalence of patients presenting with metastatic disease in our mismatch repair proficient group. And that makes sense because if these are patients that are typically with Lynch syndrome, that is perhaps a milder phenotype if you will, maybe they weren't identified early enough because the family histories weren't suggestive. So they weren't undergoing high-intensity surveillance compared to those that were in the mismatch repair deficient group that had the higher risk genes. And likely their family histories met clinical criteria for Lynch syndrome. Dr. Rafeh Naqash: Thank you so much. Now, the number that stands out in your manuscript is 10%--with individuals that had Lynch Syndrome and having mismatch repair proficient colorectal cancers. In your tumor boards that you perhaps participate in with GI, medical oncology, or other multidisciplinary tumor boards, do you try to discuss some of this early on so that implementation and uptake of whether it's NGS or germline testing is high right from the get-go? Do you try in your tumor boards to suggest to the treatment team that they should have perhaps germline testing also before they see you or at least have ordered it by the time they see you and also a full NGS panel? Or is that something that's just routinely done at your cancer center? Dr. Alicia Latham: It's routinely done at MSK. We are fortunate because of the MSK IMPACT protocol that they are routinely done. Having said that, if there is any sort of question, like I said before, oftentimes we'll talk to the oncologist about doing an orthogonal method just to verify. We also have patients that come from outside and maybe they've already had some sort of initial screening and so they wouldn't necessarily be candidates with insurance criteria, etc., for additional assessment. So we have to get a little bit creative in terms of our workup and how we can help those patients as well. But yes, we typically do. If you're suspicious, yes, we do recommend it. Dr. Rafeh Naqash: Excellent. And I know, I think, with more and more precision oncology coming up, I was speaking with a few other clinical geneticist experts at ASCO, I think incorporating individuals with clinical genomics and genetics expertise like yourself, incorporating those individuals into tumor boards, not just molecular tumor boards, but the multidisciplinary tumor boards early on, I think, could make an impact as far as testing is concerned and as far as identifying some of these things early on is concerned.  Now I would like to ask you an interesting, provocative question that you necessarily haven't addressed in the paper, but it is nevertheless interesting. So when you found or you mentioned that some of these genes have different penetrants or some are higher risk in the MSI group, the mismatch repair deficient genes, or when you think about DNA damage response, you think about neoantigens, which goes into the context of immune checkpoint inhibitors. Has there been any data or what would you think from a perspective of whether a certain gene has a higher neo antigen burden associated with it, meaning a higher number of antigens that are necessarily something that the immune system thinks that they're foreign, which helps immune checkpoint inhibitors to work? So do you think there is a difference from a neoantigen perspective in these genes suggesting that a certain tumor with a PMS deficiency versus another tumor with an MSH6 deficiency have different responses or outcomes to immune checkpoint therapy? Dr. Alicia Latham: My gut tells me perhaps. We know that when you're looking at different tumors for their MSI status or their MMR status, that MSH6, for example, mutation carriers, seem to have lower levels of that. So even just looking at our MSIsensor scores in general, they tend to be lower for MSH6 mutation carriers. So to me that signal, if it's not as pronounced, you would think that perhaps that's also there. And I think other groups have looked at that, that you're seeing that. As far as clinical response, I don't know if you're, in terms of comparing tumor to tumor, if they have the same profile, I would suspect that the response would be similar. Of course, if there's something varied, then I think that whichever profile has that higher tumor mutation burden or those neoantigens would respond better.  But I think at least as a non-oncologist, as a geneticist, and someone who's very interested in prevention, I think it's something that is incredibly important for the vaccine trials that are going on to understand and making sure that patients that we are recruiting to these trials have PMS2 and MSH6 associated Lynch syndrome, that we're not just focusing on those that we know have higher tumor mutation burden or MSI status because those are the patients we want to make sure that we're including in designing those and targeting the appropriate antigens for those trials because that is very important work that I know colleagues at other institutions are working on diligently. Dr. Rafeh Naqash: I think those are very interesting thoughts and perhaps somebody in the near future will address some of these interesting concepts.  One of the things that I didn't see in the paper that we are discussing today is what were the potential somatic, tumor somatic, events in the mismatch repair proficient colorectal cancers in the 10% that you identified that could have led to their tumor genesis. Did you look into that? Is there any subsequent work that is going on in that space? Dr. Alicia Latham: Yeah, we are looking at it subsequently, we didn't for the content of this paper. We were really focused on the MSI and mismatch repair proficiency. But yes, there was actually a study that is assessing this - really more of a pan-cancer study. We started here and one of my colleagues at MSK is working on looking at this pan-cancer and trying to understand these orthogonal methods, the tumor somatic drivers. They actually presented this abstract at ASCO this year. So trying to understand what actually did drive this. And is that something in terms of treatment that we need to be very much aware of? And I think the answer is ‘yes.' So more to come on. Dr. Rafeh Naqash: That's excellent. So hopefully, we'll see something in that space from your group in the coming months.  Another question you touched upon earlier is the implications for familial testing. So if an individual, for the sake of our listeners, if an individual comes to my clinic tomorrow with a mismatch repair proficient tumor but with a Lynch syndrome history, something similar to that I described earlier for my patient with sarcoma, what would the counseling be from a geneticist standpoint for the family? How would you explain the risk? How would you explain the tumor in that individual and then testing for the family members? Dr. Alicia Latham: So regardless of what the tumor demonstrated, I think it would be important, if this is a known Lynch syndrome patient, explaining to close family members that they have a risk of having this, a first-degree family member's 50% chance of sharing the mutation. And that's important regardless of what the tumor shows. Where I think it's more of the nuance is explaining to particularly those patient family members that test negative for Lynch syndrome. For example, in colon cancer, we say that if you have a first-degree relative with colon cancer, that, regardless of the looks like familial colon cancer without a genetic explanation, that you start colonoscopies a little sooner and you do them more frequently. So rather than 45, you start at around age 40, rather than every ten years, you repeat every five. Of course, if polyps appear, that's altered.  And so because we don't quite know if a mismatch repair colon cancer was really driven by that germline, say PMS2 mutation, could this in fact be a sporadic colon cancer that's incidental to the PMS2 mutation? Therefore, that family member that tests negative may be at an elevated risk of colon cancer and may want to consider doing colonoscopies a little sooner and a little more frequently. Having said that, I think that it's a very important conversation to have with the family members to make sure that they are very clear on that. But I think that there's a lot of work that needs to be done to understand - is it truly the case? Is there any role at all? What can we use as far as understanding kind of a different pathway for certain mutation carriers like MSH6 and PMS2? Is there something else that we're missing? So for now, I counsel my patients that I would recommend, even if you test negative, to screen a little bit earlier and a little more frequently until we understand this a little better. Dr. Rafeh Naqash: Thank you so much for that explanation. And this was a very interesting opportunity for me to help take a deeper dive into this paper, hopefully for our listeners as well. Now, a few questions about yourself, Alicia. So we like to know a little bit about the individual or individuals behind the work. So tell us a little bit about your training and your current interests and also what advice you have for early pre-investigators in the space of precision medicine, the way it's developing right now.  Dr. Alicia Latham: Sure. My training is a little bit unique, so I'm not a medical oncologist by training. I knew that I wanted to be on the prevention side, not necessarily the treatment side because when I was in medical school what was available was chemotherapy. And that wasn't for me. I didn't want to do that. And so I trained in family medicine and then completed a fellowship in medical genetics with a focus on cancer. And my clinical focus is really taking care of patients with a genetic predisposition, so at-risk patients. In that regard, I serve as Medical Director for our program at MSK called MSK CATCH, which is really for patients that have a germline susceptibility of cancer, but they want to be followed and managed at Sloan. So that's my clinical focus.   And then my research is really looking at germline predisposition, primarily Lynch syndrome, to try to understand what do we know and more importantly, what don't we know about this pan-cancer syndrome and how can we help these patients and families. Many of my studies have looked at that from understanding descriptively Lynch syndrome among different types of cancer, like small bowel cancer or the MSI status pan-cancer paper. But importantly, where we're going in the future and where I am going in the future is looking at where can we go to early detection in these patients and really increase screening because right now, the only proven effective screening for Lynch syndrome is colonoscopy, and yet it's a pan-cancer syndrome. So we have a lot of work to do. Dr. Rafeh Naqash: Thank you so much. It was really awesome to talk to you today. And thanks for explaining some of the interesting concepts around MSI-high colorectal cancers and Lynch syndromes. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Guest Biography: Dr. Alicia Latham is Medical Director at Memorial Sloan Kettering-CATCH and Assistant Attending Physician, General Internal Medicine and Clinical Genetics COIs: none  

In this episode, we discuss reproductive genetics and choices. In this conversation, we are joined by Director of The Raphael Recanati Genetics Institute, Lina Basel, and Dr Edith Coonen, Senior Clinical Embryologist at the department of Reproductive Medicine, and a Laboratory Specialist in Reproductive Genetics at the department of Clinical Genetics, Maastricht University Medical Centre. 

The Accelerators (Drs. Anna Brown, Matt Spraker, and Simul Parikh) host Clinical Geneticist Dr. Elizabeth Chao, Director of Medical Genetics at UC Irvine and Vice President and Clinical Diagnostics Laboratory Director at Ambry Genetics for a discussion about medical genetics in the oncology clinic and beyond!  We start by discussing practice models for clinical geneticists and then spend some time discussing the role of genetic testing in pancreatic cancer care. We then discuss genetic testing more generally and what the future holds for the field. Our discussion concludes with Liz sharing her training path, which started in #RadOnc, to a very successful career.  Here are some things that were discussed during the show: Publication of the PALB2 pancreatic cancer susceptibility geneNCCN Guidelines for genetic/familial high-risk assessment: breast, ovarian, and pancreaticUK NHS 100,000 Genomes ProjectAmbry Genetics - The Care ProgramPodcast art generously donated by Dr. Danielle Cunningham. Intro and Outro music generously donated by Emmy-award winning artist Lucas Cantor Santiago.The Accelerators Podcast is a Photon Media production. 

Perhaps the most noteworthy element of Osmosis from Elsevier's Year of the Zebra educational initiative is the new, open-access, peer-reviewed journal Rare. Open Research in Rare Diseases.It joins Elsevier's leading collection of 2,500 publications in science and medicine. Rare is an open journal in multiple senses because, in an unusual step, contributions are being welcomed from patients as well as scientists. “We need the patient's voice to find out what their needs and challenges are every day,” says editor-in-chief, Dr. Wendy van Zelst-Stams. “We really want to have both a clinical impact on rare disease patients and an impact on their well-being in daily life.” Dr. van Zelst-Stams is taking on this new role in addition to her work leading the Clinical Genetics Section in the Department of Human Genetics of the Radboud University Medical Center and the Dutch Society of Clinical Genetics. In this enlightening conversation with host Shiv Gaglani, you'll learn about Europe's efforts to improve care for rare disease patients, the “DNA-first” approach her program takes to reduce the diagnostic odyssey, and the types of content that will be featured in this multidisciplinary scientific journal. Mentioned in this episode: https://www.sciencedirect.com/journal/rare

This episode features Dr. Deborah Ondrasik, General Pediatrician & Dr. Wendy Chung, Director of Clinical Genetics at Columbia University in the City of New York. Here, they discuss their experience with rare genetic diseases, trends they are watching most closely with regard to rare diseases, and more.

Professor Stephen Robertson is the Curekids Professor of Paediatric Genetics. He was educated at the University of Otago graduating in Medicine in 1990. He specialized in Paediatrics and Clinical Genetics after training in Auckland and Melbourne. He was the Nuffield Medical Fellow at Oxford University and now heads the Clinical Genetics Group. Some of his work was highlighted in a documentary in 2005 ‘Lifting of the Mākutu'. In this episode, we discuss his journey into paediatrics and clinical genetics, the making of the documentary, equity in clinical genetics, volunteering with Curekids, day-to-day routines of clinical genetics, genetic counselling, controversies with 23andMe and ancestry testing, and the future of genetics. You can find the documentary here: https://www.otago.ac.nz/clinical-genetics/news-opportunities-media/lifting-of-the-makutu/Further information on Professor Robertson: https://www.otago.ac.nz/bhrc/staff/otago115051.html NB: my recording software started glitching towards the end of the interview and was unfortunately out of my control. I apologise sincerely for any negative listening experience towards the end of this show.Support the showAs always, if you have any feedback or queries, or if you would like to get in touch with the speaker, feel free to get in touch at doctornos@pm.me. Audio credit:Bliss by Luke Bergs https://soundcloud.com/bergscloudCreative Commons — Attribution-ShareAlike 3.0 Unported — CC BY-SA 3.0Free Download / Stream: https://bit.ly/33DJFs9Music promoted by Audio Library https://youtu.be/e9aXhBQDT9Y

This episode is hosted by Swati G. Patel, M.D., MS and features Sir John Burn, M.D., MBBS, BMedSci, a professor of Clinical Genetics at Newcastle University and senior leader in England's National Health Service.  Together they discuss the  10 year follow-up results of the seminal Cancer Prevention Programme (CAPP2) trial described in the Cancer Prevention Research article titled “Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo-Controlled Trial: Planned 10-Year Follow-up” which can be found here. Read our blog post Does starch prevent cancer in patients with lynch syndrome by a mechanism that might be applicable to the general population here.

Genetic sequencing is one of the most rapidly growing areas of diagnostic medicine with uses in primary prevention and surveillance planning across cancers, cardiovascular disease, and more. The session will focus on how to utilize clinical genetic screening and testing as a modality to provide evidence-based, patient-centered care in the ambulatory care setting.Speakers:Jennifer Posey, MD, PhD, Assistant Professor, Department of Molecular & Human Genetics at Baylor College of MedicineJill Tapper, MHA, CG (ASCP), System Director, Precision MedicineHitashi Bansal, MS, LCGC, Cancer Genetic Counselor at Virginia Mason Franciscan Health

As the burden of cardiovascular disease increases in the United States, the importance of enhanced screening tools, early risk prediction, and prevention strategies grows. Novel risk scoring methods, including polygenic risk scores (PRS), may help identify patients that benefit from early intervention and risk modification. In this episode, we discuss how a PRS is calculated, how to incorporate a PRS into clinical practice, and current barriers to the equitable implementation of risk scores. In terms of frontiers in clinical genetics we also discuss the burgeoning field of pharmacogenetics and how pharmacogenetics may be used to identify responders and non-responders to certain therapies. Join CardioNerds Dr. Jessie Holtzman (CardioNerds Academy Chief and Chief Resident and soon FIT at UCSF), Dr. Alaa Diab (CardioNerds Academy Fellow and Medicine Resident at GBMC), and student doctor Hirsh Elhence (CardioNerds Academy Intern and medical student at USC Keck School of Medicine) as they discuss frontiers in clinical genetics with Dr. Pradeep Natarajan (Director of Preventive Cardiology, Massachusetts General Hospital). Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig. This episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. This CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs. Pearls • Notes • References CardioNerds Cardiovascular Genomics PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - Frontiers in Clinical Genetics in Cardiovascular Prevention For common diseases like coronary artery disease, rare mutations may confer a several-fold increased risk of disease – for instance, in familial hypercholesterolemia, a single rare mutation may confer as much as a three-fold increase in risk of coronary artery disease. However, for most common diseases, the overall cumulative impact of several common genetic variants may be greater than that of a monogenetic trait. Family history is a particularly coarse predictor of CV risk, highlighting the need for polygenic risk scores. In particular, younger patients with borderline cardiovascular risk may benefit from the use of a polygenic risk score in the determination of their overall cardiovascular risk profile. A polygenic risk score (PRS) is a weighted sum of several risk-conferring alleles. The weight assigned to an allele is determined by the strength of the association between the allele and CV disease, as determined by genome-wide association studies (GWAS). The data used for genome-wide associated studies in cardiovascular disease have historically included populations primarily of European ancestry. However, more data is being collected from diverse patient cohorts to increase the external validity and broader applicability of such studies. Pharmacogenetic polygenic risk scores may be used to predict drug efficacy and toxicity, as well as to identify biologically plausible drug targets for clinical trial design. Show notes - Frontiers in Clinical Genetics in Cardiovascular Prevention What is a polygenic risk score (PRS)? Monogenic conditions are those in which a variant in a single gene causes a pathological phenotype. For example, familial hypercholesterolemia is often the result of a mutated allele in the LDL receptor gene. In contrast, polygenic risk suggests that there are variants in multiple genes that all confer risk independently, each with a small individual effect size. By aggregating many variants,

Nancy Grace teams up with 23&Me to dive into the DNA reports and  health profiles of Nancy's family who have all taken the 23&Me tests. Alongside an all-star panel, Nancy breaks down the reports to better understand the role our genetics play in our overall health.   Joining Nancy Grace today: Caryn Stark - NYC Psychologist, CarynStark.com, Twitter: @carynpsych, Facebook: "Caryn Stark" Dr. Michelle DuPre - Former Forensic Pathologist, Medical Examiner and Detective: Lexington County Sheriff's Department, Author: "Homicide Investigation Field Guide" & "Investigating Child Abuse Field Guide", Forensic Consultant, DMichelleDupreMD.com Stacey Detweiler MS, LCGC - Medical Affairs Manager, Medical Device and Clinical Genetics, 23andMe, Inc. Alisa Lehman, PhD - Senior Manager, Product Science, 23andMe, Inc.  See omnystudio.com/listener for privacy information.

Nancy Grace teams up with 23andMe to dive into the DNA reports and  health profiles of Nancy's family who have all taken the 23andMe tests. Alongside an all-star panel, Nancy breaks down the reports to better understand the role our genetics play in our overall health.    Joining Nancy Grace today:   Caryn Stark - NYC Psychologist, CarynStark.com, Twitter: @carynpsych, Facebook: "Caryn Stark"  Dr. Michelle DuPre - Former Forensic Pathologist, Medical Examiner and Detective: Lexington County Sheriff's Department, Author: "Homicide Investigation Field Guide" & "Investigating Child Abuse Field Guide", Forensic Consultant, DMichelleDupreMD.com  Stacey Detweiler MS, LCGC - Medical Affairs Manager, Medical Device and Clinical Genetics, 23andMe, Inc. Alisa Lehman, PhD - Senior Manager, Product Science, 23andMe, Inc.See omnystudio.com/listener for privacy information.

Join Ciara and Vickey as they speak with GOSH registrar Dr Menzies about her journey and experiences of working as a clinical geneticist.

This podcast is part of a miniseries of interviews with speakers from the 2022 annual conference of the Adelphi Genetics Forum - a learned society that aims to promote research and discussion concerning the scientific understanding of human heredity. Formerly known as the Galton Institute, and before that, the Eugenics Education Society, the society has changed its name to the Adelphi Genetics Forum to firmly reject and distance itself from the discredited and damaging ideas of its namesake, Francis Galton – widely viewed as the founder of eugenics.Anneke Lucassen is Professor of Genomic Medicine & Director of the Centre for Personalised Medicine at the University of Oxford and Professor of Clinical Genetics at the University of Southampton. Her talk, titled “Genomic Medicine, Diverse Data and the Language of Race, Ancestry and Ethnicity” explored the issues caused by a lack of diversity in genomic databases, and the challenges of addressing this in a way that doesn't cause additional injustice and harm. Kat Arney started by asking why it's so necessary to do this work.You can find out more about the Adelphi Genetics Forum, including their grants, awards and publications, at adelphigenetics.org You can check out the rest of this series on the Genetics Unzipped podcast feed – just search for Genetics Unzipped on Spotify or wherever you get your podcasts. This series was produced by the team at First Create The Media – that's Kat Arney, Sally Le Page and Emma Werner, with help from Ed Prosser and Frankie Pike. Our music is Drops of H2O by J. Lang, licensed under Creative Commons.

In 2012, the 100,000 Genomes Project was announced, the same year we started this podcast!Back in 2015 we did an episode about the 100,000 Genomes Project so we're excited to revisit this massive project today with Dr. Julian Barwell, who is a clinical geneticist and has countless titles but today's most relevant one is the operational clinical lead of the 100,000 Genome project.After finishing his Clinical Genetics training (2001-2007) at Guy's, St George's and the Royal Marsden from the University of London; Dr. Barwell started as a consultant in Clinical Genetics in Leicester. He runs specialist clinics in inherited cancer susceptibility; non-alcoholic fatty liver disease and susceptibility to hepatitis, cirrhosis and hepatocellular carcinoma; Von Hipped Linda syndrome and Neurofibromatosis type 2. He has over 60 publications and helped coin the internationally known phrase, the 'Angelina Jolie effect' on referrals to inherited breast cancer clinics. He also developed the first YouTube channel for Clinical Genetics that has been viewed in over 100 countries and developed the Supporting Families with Cancer projects in association with the Genetics Education Centre (GENIE) at the University of Leicester. He is the clinical lead for the delivery of Paediatrics, Obstetrics & Gynaecology, Non-Malignant Haematology and Clinical Genetics national portfolio research studies (CRN) in the East Midlands. He is the rare disease lead for the 100,000 Genome Project in Leicester and the public and patient involvement clinical lead for the East of England Genomics Medicine Centre with the aim of reducing inequality of access to Genomic Medicine. He is the designer of the genome project eligibility criteria wheels for Health Education England and is on the Genomics England committee for patient involvement and access to genomics for black and minority ethnic groups. He is a national clinical advisor to the National Hereditary Breast Cancer Helpline and helped develop the award winning Prostaid male health App and is clinical lead of the United Against Prostate Cancer project, establishing tumour BRCA testing. He is joint clinical lead of the Paediatric and Genetics Clinical Research Facility at the Leicester Royal infirmary and is establishing a fragile X syndrome research group and patient self-navigation App project with the Genomic Medicine Service Alliance. He is a senior author of the newly commissioned book, Clinical Genetics and Genomics at a Glance as well as a children's book on DNA. On This Episode We Discuss:Ten years of the 100,000 Genomes Project (2012-2022)Advantages of using digital pedigrees tools such as the one developed by TrakGeneWhy it's important to have genomes from various ancestries representedImportance of utilizing digital pedigrees How the 100,000 Genome Project is going to change the role of genetic counselorsReclassifying variants as data is continuously being analyzedIf you want to learn more about what it's like to be a clinical geneticist, check out this article which follows Dr. Barwell through a day in the life, and you can find a list of Genomics England's publications here.To learn more about TrakGene, the pedigree drawing tool and clinical genetics database software company that we mentioned in this episode, you can head to their website or follow them on Twitter, Facebook, LinkedIn, and YouTube. You can also follow Dr. Barwell on Twitter and Facebook!Don't forget to enter our upcoming giveaway via social media next week for a lifetime subscription to TrakGene and a copy of “The Patient Will See You Now” by Dr. Eric Topol. You can also use code “DNATODAY” for a year free trial for TrakGene. Stay tuned for the next new episode of DNA Today on next Friday, November 4th, 2022 where we'll be defining quality genetic tests with Blueprint Genetics! In the meantime, you can binge over 205 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com.

In honor of Breast Cancer Awareness Month, today's episode highlights Rachel Silver-Cohen's special friend and real-life superhero, Stephanie Robin. Stephanie meets the gals on the corner of Audacity & Advice to share her courageous story; first battling Stage II Breast Cancer and then having to tackle a Stage IV diagnosis after her cancer metastasized to both lungs. Initially under the pristine care of Dr. Louise Morrell, Medical Oncology Specialist in Boca Raton, Florida she quickly learned the necessity of knowing family history as it relates to the BRCA1 & BRCA2 genes and the risks associated with these mutations. Subsequently, Dr. Mark E. Robson, Associate Attending Physician of the Clinical Genetics & Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York City invited Stephanie to join his clinical trial. Fourteen years later, Stephanie is N.E.D. "No Evidence of Disease!" To this day, Stephanie maintains her mantra, "Pink Is Not Just A Color, It's An Attitude." As creator and founder of Think Pink Rocks, a non-profit organization whose mission is to raise awareness about early detection of and genetic testing for breast cancer and to provide funding for screening, treatment and research, Stephanie is a Survivor, a Warrior and a Real Life Superhero who continues to advocate for awareness helping both men and women in an effort to save lives. She not only walks the walk daily, but today she candidly talks the talk about her personal journey and what life feels like beyond beating Metastatic Breast Cancer. If you're looking to hear a success story, this is an episode you won't want to miss! For More Information on Think Pink Rocks or to contact Stephanie with questions or concerns, please visit www.ThinkPinkRocks.org Follow Think Pink Rocks on Instagram @ThinkPinkRocks Have Additional Comments? Questions? Concerns? Email Us: UnpolishedTherapy@gmail.com Find Us On Facebook & Instagram @UnpolishedTherapy and on Twitter @UnTherapy Donations to Think Pink Rocks will benefit 501(c)(3) charitable organizations and will be contributed to the dedicated Think Pink Rocks Breast Cancer Research Funds at each of Memorial Sloan Kettering Cancer Center, the Breast Oncology Center at the University of Michigan's Rogel Cancer Center and the Boca Raton Regional Hospital/Lynn Women's Health and Wellness Institute.

In the United States, shortly after birth, every newborn receives a series of screening tests to identify treatable diseases. Every September we celebrate this amazing system of research, public health, and clinical care that saves the lives of babies every day with Newborn Screening Awareness month.  Neonatal screening also occurs around the world and many countries are working on innovative approaches to use genomics to significantly expand, or improve, our ability to screen, diagnose, and treat hundreds if not thousands of additional diseases. We are excited to feature one of these innovators on the Newborn Screening Spotlight, Dr. David Bick who, is the Principal Clinician for the Newborn Genomes Programme at Genomics England.  Genomics England is undertaking an effort to include genomics in neonatal screening.   Prior to his work in England, he was the Chief Medical Officer and a faculty investigator at the HudsonAlpha Institute for Biotechnology.  He came to HudsonAlpha from the Medical College of Wisconsin where he was Professor in the Department of Pediatrics and the Department of Obstetrics & Gynecology at the Medical College of Wisconsin.  At the Medical College of Wisconsin he was the Director of the Clinical Sequencing Laboratory, Director of the Advanced Genomics Laboratory at Children's Hospital of Wisconsin, Medical Director of the Genetics Clinic at Children's Hospital of Wisconsin, and Chief of the Division of Genetics in the Department of Pediatrics at Medical College of Wisconsin.    Dr. Bick received his medical degree from George Washington University School of Medicine in 1981 and completed his residency in Pediatrics at Yale-New Haven Hospital in New Haven, CT.  At the Yale University School of Medicine, Dr. Bick completed a fellowship in Human Genetics and Pediatrics in 1986, followed by a post-doctoral research fellowship in Human Genetics in 1987.  Dr. Bick is board certified in Pediatrics, Clinical Genetics, and Clinical Molecular Genetics.   He is a leader in the field of genomic medicine and has published numerous peer-reviewed articles, chapters, and reviews.  Dr. Bick's laboratories at the Medical College of Wisconsin and Children's Hospital of Wisconsin were the first in the world to offer whole genome sequencing as a clinical test.  He also developed the first Genomic Medicine Clinic in the United States. Join us as we learn about the role of genomic sequencing of newborns.   Podcast Interview Questions for Dr. David Bick   Bick, thank you for joining us for the newborn screening SPOTlight podcast, we would love for our listeners to get know you and the impact you've made on clinical genomic medicine, newborn screening research. You're a pediatrician, researcher, and leader in genomic medicine. How did you get involve with newborn screening research?   You were a faculty in the Department of Pediatrics and the Department of Obstetrics & Gynecology at the Medical College of Wisconsin, where your laboratory was the first to offer whole genome sequencing as a clinical test. What advice can you share for others who are interested in proposing the implementation of genome sequencing in their hospitals?   You have now moved to the UK to be the Principal Clinician for the Newborn Genomes Programme at Genomics England. Can you tell our listeners more about this program?   From your experiences at the Screen4Care consortium and the European collaborative Innovative Medicines Initiative, what are lessons that we in the US can learn from?   In your recent publication titled “Newborn Screening by Genomic Sequencing: Opportunities and Challenges,” you describe the need for “standardization of data formats and analytical approaches within and even between health systems” to support newborn screening by genome sequencing. There are differences between the UK and US health care delivery system. How do you envision this process of standardization in the UK? How can the US with its various health care delivery systems and health insurance plans be able to adopt a similar approach?   Are you involved in training the next generation of pediatrician nd what do you tell them about newborn screening research?   What role could NBSTRN play to support international efforts in advancing rare disease research and screening for diseases for which early intervention may improve outcome?   What does NBS research mean to you?        

Dr. Ora Gordon, Regional Medical Director of the Providence Center for Clinical Genetics & Genomics discusses the latest innovation in early cancer detection. Stewart Glickman, Head of Energy Research at CFRA gives his thoughts on the oil market. Bloomberg Quicktake's Scarlet Fu discusses the importance of House Speaker Nancy Pelosi's trip to Taiwan. And we Drive to the Close with Abhay Deshpande, Chief Investment Officer at Centerstone Investors. Hosts: Tim Stenovec and Kriti Gupta  Producer: Sara LivezeySee omnystudio.com/listener for privacy information.

Dr. Ora Gordon, Regional Medical Director of the Providence Center for Clinical Genetics & Genomics discusses the latest innovation in early cancer detection. Stewart Glickman, Head of Energy Research at CFRA gives his thoughts on the oil market. Bloomberg Quicktake's Scarlet Fu discusses the importance of House Speaker Nancy Pelosi's trip to Taiwan. And we Drive to the Close with Abhay Deshpande, Chief Investment Officer at Centerstone Investors. Hosts: Tim Stenovec and Kriti Gupta  Producer: Sara LivezeySee omnystudio.com/listener for privacy information.

Join us with Dr. Richard Boles as we learn more about how to interpret genetic test results. The landscape today for a mitochondrial disease diagnosis is rapidly changing and now includes some genetic testing for most patients. However, many families are confused even further by the results. What is an VUS? What do the specific mutations mean? What does 30% depletion mean? Learn the nuts and bolts of interpreting today's genetic tests from Dr. Boles in this informative discussion. About the Speaker Dr. Boles completed medical school at UCLA, a pediatric residency at Harbor-UCLA, and a genetics fellowship at Yale. He is board certified in Pediatrics, Clinical Genetics and Clinical Biochemical Genetics. His current positions include Associate Professor of Pediatrics at the Keck School of Medicine at USC, attending physician in Medical Genetics and General Pediatrics at Childrens Hospital Los Angeles, and Medical Director of Courtagen Life Sciences. Dr. Boles practices the "bedside to bench to bedside" model of a physician-scientist, combining an active clinical practice in metabolic and mitochondrial disorders with clinical diagnostics and basic research through Courtagen. Dr. Boles' clinical and research focus is on polymorphisms (common genetic changes) in the DNA that encodes for mitochondrial genes, and their effects on the development of common functional disorders. Examples include migraine, depression, cyclic vomiting syndrome, complex regional pain syndrome, autism and SIDS.

Tools for Testing Mitochondrial Disorders: The Latest Advances in Genetics and Genomics Guest speaker Dr. Richard Boles from Children's Hospital Los Angeles and Courtagen Life Sciences, Inc. to discuss: What is genomic sequencing and how does it change testing for mitochondrial disorders? Is NextGen testing appropriate for all people with suspected mitochondrial disease? How can DNA sequencing change information available about family inheritance of mitochondrial diseases? Do advances in genomic sequencing impact treatment options for Mito patients? About The Speaker: Dr. Boles completed medical school at UCLA, a pediatric residency at Harbor-UCLA, and a genetics fellowship at Yale. He is board certified in Pediatrics, Clinical Genetics and Clinical Biochemical Genetics. His current positions include Associate Professor of Pediatrics at the Keck School of Medicine at USC, Director of the Metabolic and Mitochondrial Disorders Clinic at Children's Hospital Los Angeles, and Medical Director at Courtagen Life Sciences Inc. Dr. Boles practices the "bedside to bench to bedside" model of a physician-scientist, combining a very active clinical practice in metabolic and mitochondrial disorders with basic research as Director of a mitochondrial genetics laboratory at the Saban Research Institute. Dr. Boles' clinical and research focus is on polymorphisms (common genetic changes) in the maternally-inherited mitochondrial DNA, and with new technology in the nuclear DNA (chromosomes), and their effects on the development of common functional disorders. Examples include migraine, depression, cyclic vomiting syndrome, complex regional pain syndrome, autism and SIDS. He has 50 published papers on mitochondrial disease. Dr. Boles is responsible for the final review of DNA sequences at Courtagen.

Talking points include: What is the immune system and why is it important? Infection and mitochondrial disease Immune function in mitochondrial disease About The Speaker: Dr. Peter McGuire Dr. Peter McGuire received his MBBCh (with Honours) from the Royal College of Surgeons in Ireland in 2003. Following a combined residency in Pediatrics and Medical Genetics at Mount Sinai Medical Center in New York City, he remained as an Assistant Professor in the Program for Inherited Metabolic Diseases at Mount Sinai. Dr. McGuire is board certified in Pediatrics, Clinical Genetics and Biochemical Genetics. In 2010, Dr. McGuire moved to the National Human Genome Research Institute (NHGRI) at the National Institutes of Health to join the Physician Scientist Development Program. He was appointed to the position of tenure track Investigator in 2016. Throughout his career, Dr. McGuire has been focused on improving the care of patients with disorders of mitochondrial metabolism. By combining his training in Immunology and Biochemical Genetics, he has fashioned a translational research program to understand the interplay between mitochondrial metabolism and the immune system. As Head of the Metabolism, Infection and Immunity Section (MINIS) at NHGRI, Dr. McGuire and his team study the interplay between metabolism and the immune system in patients with inborn errors of mitochondrial metabolism. The group focuses on two aspects of immunometabolism: 1) Immune system activation and end-organ mitochondrial metabolism The focus of the group's research on immune system activation and end-organ metabolism is based on the clinical observation that infection is a major cause of morbidity and mortality in patients with mitochondrial disease. The MINIS uses animal models, combined with infectious organisms, to yield insights into the metabolic perturbations seen in disorders of mitochondrial metabolism during infection and to identify potential targets for intervention. 2) Role of mitochondria in immune cell function The group also studies mitochondrial metabolism and immune cell function. Immune cells drastically alter their metabolic programming during activation and differentiation. The deficiencies present in patients with mitochondrial disease may affect these processes. The group developed a clinical protocol in the National Institutes of Health (NIH) Clinical Center, called the NIH MINI Study: Metabolism, Infection and Immunity in Inborn Errors of Metabolism (NIH Clinica

In this week's episode Dr Scott shares his journey to becoming a consultant clinical geneticist and the Chief Medical Officer (CMO) at Genomics England. We delve into his passion for clinical genetics, the misconceptions and the barriers medical professionals and general public have understanding the true nature of genomics.   Richard shares his desire to harness the power of genomic technologies for the benefit of all patients in mainstream healthcare. We spend time understanding the path he took to becoming a consultant and CMO, in such a niche medical specialty. We discuss the role of Genomics England and how they are helping improve the diagnosis and treatment of patients in the NHS through their scientific research. Richard explains how pivotal their work is for the future of healthcare and why it is so important communities from across the UK become actively informed and involved.  Learn more about Richard: Dr Richard Scott is Chief Medical Officer at Genomics England, Consultant and Honorary Associate Professor in Clinical Genetics at Great Ormond Street Hospital for Children and the UCL Institute of Child Health where his practice focuses on diagnosing children with rare multisystem disorders.  Richard trained in medicine at Cambridge University and University College London. He specialised in Paediatrics and subsequently Clinical Genetics in London and completed his PhD on childhood cancer syndromes at the Institute of Cancer Research. Twitter: @Rich_Genomics https://www.genomicsengland.co.uk/ ------------------------------------- Episode sponsored by MySuture  MySuture™  is an all in one suture practice kit and digital learning platform with direct access to Surgeon advice & training. With this all in one suture practice kit and the MySkills™ digital learning platform, you can learn to suture anytime, anywhere.  The all in one suture simulation kit includes high quality silicone made of advanced nontoxic materials, with height simulation skin, 14 pre-cut wounds, 3 layers including skin, subcutaneous fat and muscle with a mesh reinforcement to provide suture retention, mimic natural anatomy and create a true to life texture.  Buy your suture kit now at: mysuture.com  MySuture Socials: Twitter | Instagram ------------------------------------- Check out our latest platform Peerr Where healthcare professionals learn from the best educators - your peers! ✍️ Make your own quizzes for revision - An invaluable learning tool

In this week's podcast, we wrap up our celebration of National Volunteer Month by highlighting some of the amazing people who dedicate their time and talents to making Women Who Code the amazing global community it is. Women Who Code Conversations: Sierra OBryan, Senior Software Engineer at Twitter and WWCode Mobile Leadership Fellow, and Vui Nguyen, Senior iOS Consultant at Atomic Robot, and WWCode Mobile Track Lead, discuss their experiences volunteering for Women Who Code, and how it has enriched their lives and careers. https://www.womenwhocode.com/blog/wwcode-podcast-40-the-importance-and-benefits-of-volunteering-wwcode-leaders Women Who Code Talks Tech: How to Translate Big Data and DevOps Into Clinical Genetics Applications In celebration of DNA Day on April 25th, we have a discussion on How to Translate Big Data and DevOps Into Clinical Genetics Applications, given by Angelina Uno-Antonison, Software Architect, Genomics, at the UAB School of Medicine. This talk was featured at CONNECT Digital 2020, and remember, the next Women Who Code CONNECT conference is right around the corner and is taking place on May 26th, 2022. https://www.womenwhocode.com/blog/how-to-translate-big-data-and-devops-into-clinical-genetics-applications Women Who Code Career Nav: A panel featuring Women Who Code Leaders talking about how YOU can become a Women Who Code volunteer. Learn how to come up with a topic, submit a talk, and elevate your professional profile while sharing your expertise with our global community. Featuring WWCode Mobile Fellow Sierra OBryan, WWCode Data Science Fellow Zareen Naowal, and WWCode Python Fellow Anjali Menon, and moderated by WWCode Community Manager Sapphire Duffy.

#TheRisingTide Episode 5In this episode of The Rising Tide Podcast, Dr. Bryan Gall sits down with the Center for Genomic Interpretation to discuss, among other things, clinical variant interpretation. For example, what might cause two labs to report the same genetic variant differently?Podcast Introduction from 00:00 Interview begins at 08:18 This interview was initially completed in 2021.

We are excited to share that Kourtney Kardashian recently featured in DNA Today in an article on Poosh, “How Genetics Play the Ultimate Role in Health”. Our host, Kira Dineen, shares insight on genetic counseling and epigenetics. The Chief Medical Officer of Mitera, Dr. Kathy Salari, joins the show. Mitera is a telehealth company that offers a unique care model that uses remote technologies and subspecialty medical oversight to responsibly democratize access to reproductive genetic testing. On this episode, Dr. Salari will be sharing about Mitera's at-home reproductive genetic testing options including non-invasive prenatal screening and carrier screening. Dr. Kathy Salari is a maternal-fetal medicine subspecialist with expertise in caring for high-risk pregnancies. Her clinical work primarily focuses on reproductive genetics and fetal imaging. She received her Bachelor's degree in Molecular Genetics from U.C. Berkeley in 2001 and her medical degree from U.C. San Diego in 2008. She then went on to complete her residency in Obstetrics & Gynecology followed by a fellowship in Maternal-Fetal Medicine at the University of Michigan in 2014. Following completion of her training, she began her clinical career as a maternal-fetal medicine specialist in the San Francisco Bay Area. In a period of two years she was named Chair of Clinical Genetics as well as the Director of Fetal Imaging and Perinatal Genetics at Palo Alto Medical Foundation. During her tenure as the director of a high volume fetal imaging center and maternal-fetal medicine group, her passion for timely and accurate diagnosis of birth defects and delivery of evidence-based obstetric care was emboldened. Driven by a vision for bringing subspecialty reproductive health expertise to every pregnant person across the country, she founded Mitera in 2019. By employing a telehealth platform for reproductive genetic testing, she hopes to bridge gaps in maternity care and broaden access to the responsible delivery of diagnostic technologies across the country. On This Episode We Discuss:Inspiration behind MiteraGenetic conditions included in Mitera's 23Pears carrier screening kitKira's experience with 23Pears and what consider she is a carrier ofInformed consent process for ordering genetic testingHow results are shared with patientsInformation included in Peaches&Me (Non-Invasive Prenatal Screening)Why Mitera's tests do not include microdeletions (NY Times article referenced) How patients can order Mitera testing >>>>> Insert YT Mitera Video

In existence for over a century, the National Institutes of Health (NIH) is arguably one of the most important agencies of the federal government. Its work is so critical that it often enjoys rare and widespread bipartisan support. In this special bonus episode, President Clinton and nationally recognized experts share first-person accounts and unique perspectives of how the Clinton administration's unprecedented investment in research and science at NIH led to some of the most impactful scientific breakthroughs in the last century – including developing antiretroviral treatments for HIV/AIDS, accelerating research which ultimately made it possible to develop COVID-19 vaccines, and the sequencing of the human genome. This episode features talks by: President Bill Clinton, 42nd President of the United States, Founder and Board Chair, Clinton Foundation  Dr. Donna E. Shalala, Secretary of Health and Human Services in the Clinton Administration Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases at the NIH Dr. John I. Gallin, NIH Associate Director for Clinical Research who served as the inaugural chief scientific officer of the NIH Clinical Center Dr. Gary Nabel, President & CEO of ModeX Therapeutics and the first director of the NIH Dale and Betty Bumpers Vaccine Research Center Dr. Harold Varmus, the Lewis Thomas University Professor of Medicine at Meyer Cancer Center of Weill Cornell Medicine, former Director of NIH, and Nobel Prize winning scientist Dr. Wendy Chung, Director of Clinical Genetics at Columbia University Dr. Francis Collins, longstanding former NIH Director and Director of the National Human Genome Research Institute Dr. Charles Rotimi, Director of the Trans-NIH Center for Research on Genomics and Global Health This podcast was adapted from an event held in partnership with the Clinton Presidential Center and the University of Arkansas Clinton School of Public Service as part of the Kumpuris Distinguished Lecture Series. To learn more, visit www.clintonpresidentialcenter.org.  See omnystudio.com/listener for privacy information.

Clinical Geneticist at the Children's Hospital of Philadelphia, Dr. Ian Campbell, Principal Investigator in the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital, Dr. Bimal Chaudhari, and Consultant in Clinical Genetics at Great Ormond Street Hospital, Dr. Ajith Kumar discuss the biggest challenges patients face in clinical genetic care, how to integrate feedback to improve patient care, and navigating systemic barriers to improve accessibility of care in clinical genetics. Hosted by DNA Today's Kira Dineen.

DNA Today's host Kira Dineen is also one of the hosts of the PhenoTips Speaker Series. This monthly live webinar focuses on relevant genetics topics by featuring discussions with thought leaders and experts in genomic medicine. In this podcast episode we are sharing an installment of the PhenoTips Speaker Series, “Advances in Rare Disease Diagnosis”, which is hosted by Kira's colleague, Dr. Pawel Buckowicz.With over 6,000 rare diseases, reaching diagnosis is a long and arduous process for the 300 million people worldwide affected by rare disease. Advances in technology, collaboration, bioinformatics and more hold the promise to end or reduce this diagnostic odyssey. To address these advancements, PhenoTips invited Dr. Stephen Kingsmore, Dr. Marshall Summar, and Dr. Ellen Thomas.Dr. Stephen Kingsmore, the inaugural President & CEO of the Rady Children's Institute for Genomic Medicine, previously held roles as Director of the Center for Pediatric Genomic Medicine at Children's Mercy Hospital, President & CEO of the National Center for Genome Resources, and Chief Operating Officer of Molecular Staging Inc. Dr. Kingsmore's rapid genome diagnosis was ranked as one of the top 10 medical breakthroughs of 2012 by TIME magazine, and his 26-hour genetic sequencing garnered him the Guiness World Record for the fastest genetic sequencing in the world.Dr. Marshall Summar is the Margaret O'Malley Professor of Genetic Medicine and Chief of the Division of Genetics and Metabolism at Children's National Hospital. In addition, he launched and directs Children's National's first clinical Rare Disease Institute, the largest clinical division of its kind treating over 8,000 rare disease patients per year. Dr. Summar currently chairs the National Organization for Rare Disorders' Scientific and Medical Advisory Committee as well as Co-Chairing the Research Committee for the Rare Disease Diversity Coalition. His research focuses on adapting knowledge from rare diseases to mainstream medicine.Dr. Ellen Thomas is Clinical Lead for Rare Disease and Clinical Safety Officer at Genomics England, Clinical Advisor to the Genomics Unit at NHS England and Improvement, and a Consultant in Clinical Genetics at Guy's and St Thomas' NHS Trust. As part of the Genomics England Science Team led by Professor Sir Mark Caulfield, she has worked on delivery of the 100,000 Genomes Project, and now focuses primarily on Genomics England's contributions to the Genomic Medicine Service, as well as supporting the interface between research and clinical care for participants and researchers within the National Genomic Research Library.In this panel discussion moderated by Dr. Pawel Buczkowicz, leading rare disease clinicians and researchers address:The latest technological advances helping to reduce the diagnostic odyssey for patientsThe greatest challenges faced by patients and clinicians and methods to overcome themThe role of bioinformatics in the analysis of large datasets generated from sequencingThe role of rare disease diagnosis in precision medicine.Tune in for the next PhenoTips Speaker Series with our host Kira Dineen! Join us live on March 23rd from 11 am – 12:15 pm EST, for the 18th installment of PhenoTips' Speaker Series, “Future of Hereditary Cancer Genetic Counseling”. The Future of Hereditary Cancer Genetic Counseling is a panel discussion and interactive Q & A with Jill Stopfer, Associate Director of Genetic Counseling at the Dana Farber Cancer Institute, Jessica Corredor, Senior Genetic Counselor at the University of Texas MD Anderson Cancer Center, and Emily Nazar, Lead Cancer Genetic Counselor at Genome Medical. Register for free here. Stay tuned for the next new episode of DNA Today where we wrap up our rare disease month celebrations with Keith McArthur from Unlocking Bryson's Brain podcast! New episodes are released on Fridays. In the meantime, you can binge over 170 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com. Preparing for a career in genetics? Keck Graduate Institute in Claremont, California, is a recognized leader in healthcare and biotech education and offers two master's programs ideal for those looking to impact the genetics field. The master's in human genetics and genetic counseling will train you to become an innovative, collaborative, and caring genetic counselor. The master's in human genetics and genomic data analytics will give you hands-on experience with the technologies and information revolutionizing the future of medicine. Learn more about KGI's innovative programs by visiting kgi.edu. (SPONSORED)PerkinElmer Genomics is a global leader in genetic testing focusing on rare diseases, inherited disorders, newborn screening, and hereditary cancer. Testing services support the full continuum of care from preconception and prenatal to neonatal, pediatric, and adult. Testing options include sequencing for targeted genes, multiple genes, the whole exome or genome, and copy number variations. Using a simple saliva or blood sample, PerkinElmer Genomics answers complex genetic questions that can proactively inform patient care and end the diagnostic odyssey for families. Learn more at PerkinElmerGenomics.com. (SPONSORED)

“I hope it will happen in our lifetime, that we will start to learn how to use the totality of information that's available on tumours. And I don't just mean genomics, I mean any of it - including all the bits around the tumour, the microenvironment, the immune system. In the last 10 years alone, cancer research has grown phenomenally. It's been extraordinary to be involved in all of it. It's a very real privilege to be to be in this space.”  In this week's episode of The G Word, Chris Wigley is joined by Serena Nik-Zainal, a consultant in clinical genetics, a Cancer Research UK Advanced Clinical Scientist at the University of Cambridge and an Honorary Consultant in Clinical Genetics at Addenbrooke's Hospital in Cambridge. She was the first woman to win the Josef Steiner Cancer Research Award in 2019.  Serena discusses sharing data, personalised treatment for cancer patients and the impact of the 100,000 Genomes Project. She also talks about the involvement of participants, cancer research and the need for genomic data diversity. 

Dr. Brocha Tarshish is a medical geneticist based in South Florida. She is a 2004 graduate of Sackler School of Medicine. She completed a preliminary year in internal medicine at Maimonides Medical Center in 2005, and then completed a residency in Obstetrics and Gynecology at North Shore University Hospital in 2009. After working in Obstetrics and Gynecology for a short time, she then completed a residency in Medical Genetics at Emory University. Dr. Tarshish is board-certified in Clinical Genetics and Genomics. After practicing full-time as a faculty member at the University of Miami for a few years, she began working as a Medical Director for the laboratory division of eviCore Healthcare. In addition to working for eviCore, she also works part-time as a Clinical Geneticist for Nicklaus Children's Hospital. Dr. Tarshish also works as a Clinical Instructor at NOVA Southeastern University in the physician assistant training program. She has published articles in peer-reviewed journals in the field of medical genetics. Dr. Tarshish lives in Miami Beach with her husband and three children. 

It has long been thought that the root causes of intellectual disability cannot be treated or cured. However, a growing body of research suggests that a rare genetic condition known as Kabuki syndrome (which we explored in the previous episode) might offer a path forward in being able to treat, and partially reverse the effects of some types of intellectual disability.On this episode of One Rare Heart we speak with a physician/scientist at the forefront of this research, Dr. Hans Bjornsson, and hear about how his search for answers is also calling into question the medical establishment's long-held dogma surrounding intellectual disability.As Dr. Bjornsson seeks to provide therapeutic options that could help bolster intellect in the neurodivergent community, the ramifications of his work could be immense, especially for individuals with Kabuki syndrome and related disorders. Take this opportunity to engage with Dr. Bjornnson's exciting research as he shares about his work and as we learn more about the needs of this at-risk and unique community that he seeks to serve.EPISODE GUESTDr. Hans Bjornsson – Dr. Bjornsson is a physician/scientist who runs research laboratories at the University of Iceland and at Johns Hopkins University. Both of his labs focus on identifying the causes of intellectual disability in Kabuki Syndrome, and on the development of therapeutic treatments that could potentially help ameliorate the effects of intellectual disability in individuals with Kabuki, and related disorders. At Johns Hopkins he is Associate Professor of Genetics and Pediatrics, as well as Associate Director of the Epigenetics & Chromatin Clinic. He is also a Full Professor of Translational Medicine and Pediatrics at the University of Iceland, and is Director of Clinical Genetics at the University of Iceland Hospital.SUPPORT BJORNSSON LABSPlease consider supporting Dr. Bjornsson and his groudbreaking research. You can find more information about his work, his laboratories and how to support this research HERE.KABUKI SYNDROME - CLINICAL TRIALSIf you or someone you know is interested in taking part in the HOPE clinical trial mentioned in this episode (which is a collaboration between Johns Hopkins University and Oryzon), or other related studies, you can find more information by visiting the research page of the Kabuki Syndrome Foundation.NEURO-DIVERSITYClick HERE to learn more about intellectual disability as a form of neuro-diversity, and how you can better support individuals who are neuro-divergent.

DNA Today's host Kira Dineen is also the host of the PhenoTips Speaker Series. This monthly live webinar focuses on relevant genetics topics by featuring discussions with thought leaders and experts in genomic medicine. In this podcast episode we are sharing an installment of the PhenoTips Speaker Series, “The Adoption and Impact of Digital Tools in Genetic Counseling”. This episode features a panel of genetic counselors, who are digital champions at their respective practices, discuss the impact of digital tools on their departments as well as their experience and insights championing the adoption of digital tools.As genetic testing becomes increasingly common, genetic counselors face increasing demand that they struggle to meet due to low numbers of genetic professionals in clinical care. Supplementing genetic counseling practice with digital tools is necessary in order to provide essential services while mitigating burnout, but genetic counselors and genetic departments face significant barriers to adoption. To help lessen these barriers, PhenoTips invited genetic counselors Scott Weissman, Amy Taylor and Andrew McCarty to share their experiences becoming digital champions, gathering departmental support, and the clinical impact their departments have experienced since adoption.Dr. Amy Taylor is the Lead Consultant Genetic Counsellor at Cambridge University Hospitals NHS Foundation Trust. With over a decade of experience in Genetic Counseling, she heads a team of 14 Genetic Counsellors who provide high quality service to patients in the East Anglia region. Her specialist interests include cancer genetics, cardiac genetics and neurofibromatosis type 2, and for the last six years she has been a member of the UK Cancer Genetics Group Council. Amy's articles have been published in prestigious journals such as Clinical Genetics and Journal of Medical Genetics.Andrew McCarty is a Laboratory Genetic Counselor at Perkin Elmer Genomics. He also operates a private practice based out of Pittsburgh called Clover Genetics working to improve access to genetic services. With a passion for providing genetic education to healthcare providers, students, and individuals seeking care, Andrew has authored numerous scholarly articles, including research on the use of the digital tool Proband in pedigree construction and assessment published in the Journal of Genetic Counseling.Scott Weissman, an NSGC Digital Ambassador, has over 15 years of experience in adult-onset genetic disorders and cancer genetics. He is the founder Chicago Genetic Consultants, LLC and the Cancer Services Lead at tele-genetics provider Genome Medical. Scott has worked with patient advocacy groups (FORCE, Bright Pink, CCARE) as well as lectured across the country on a variety of topics related to genetic counseling and testing. Scott's scholarly articles have been published in prestigious journals such as Genetics in Medicine, Cancer, The Journal of the American Medical Association, Journal of Genetic Counseling, and many more.In this panel discussion moderated by DNA Today's Founder, Producer and Host, Kira Dineen, CGC, Amy Taylor, Scott Weissman, and Andrew McCarty draw on personal experiences to provide insights on:The clinical impact of digital tools in genetic departments through examples from their years of practiceTheir journey of gathering departmental support for adoption of digital toolsThe techniques that allow genetic counselors and genetic departments to overcome challenges in digital tool adoption.Stay tuned for the next new episode of DNA Today on November 12th! This episode will be another insightful installment of the PhenoTips Speaker Series where we explore the future of genetic counseling with Amy Sturm and Erynn Gordon. New episodes are released on the first and third Friday of the month, with some bonus episodes. In the meantime, you can binge over 160 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes in 2021 are also recorded with video which you can watch on our YouTube channel. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com. Do you or someone you know have Prader-Willi syndrome? Harmony Biosciences is looking for people with Prader-Willi syndrome to enroll in a new clinical study in the United States. Harmony Biosciences will be studying the safety and impact of an investigational medication on excessive daytime sleepiness, cognition, and behavioral function in people with Prader Willi syndrome. Check out their website to learn more about the clinical study and refer a patient to a study center. More clinical studies for genetic conditions can be found at KnowRare.com. (SPONSORED)Do you work in a lab? Want to receive rewards when you order supplies? Check out Thermo Fisher Scientific's Aspire program, it's a rewards program created with scientists, like you, in mind. All members receive a free full size trial product every year. Points are earned every time you use or purchase products. Rewards include science themed apparel like a zip up DNA hoodie! Check it out at ThermoFisher.com/aspire-DNAtoday and for a limited time receive 500 bonus points. ThermoFisher Terms and Conditions: Open only to eligible participants in the US (excluding Puerto Rico) and Canada (excluding Quebec). Eligible participants must complete the enrollment process for the Aspire member program in order to be enrolled in the program and receive rewards and benefits. Enrollees must confirm their health care professional or government employment status during time of enrollment. For full terms and conditions of the program, go to thermofisher.com/aspire/tc. Offer is void where prohibited, licensed, or restricted by federal, state, provincial, or local laws or regulation or agency/institutional policy. Other restrictions may apply. (SPONSORED)Polygenic Risk Scores are no longer science fiction. Allelica has created a secure and trusted platform for Polygenic Risk Score analysis and reporting. Health systems and clinical laboratories can be equipped with Allelica's cutting-edge tools to reduce the impact of common disease through genomic medicine. Allelica's Polygenic Risk Scores for common diseases have the highest predictive power on the market. This allows physicians to more effectively help patients lower their risk of life-threatening diseases. Learn more at Allelica.com. Empowering the next generation of clinical genomics. (SPONSORED)For centuries, humanity has imagined a magical fountain that could unlock eternal youth. New scientific advances suggest this might actually be a reality in the not-too-distant future. Journalist Keith McArthur explores the mysteries of aging in “Unlocking The Fountain” from CBC Podcasts, where you'll meet dreamers, skeptics and cutting edge scientists, including those who believe that the first person who will live to 150 years old has already been born. Keith McArthur hosted “Unlocking Bryson's Brain”, which we recommended last year, and now you can tune into his brand new podcast! We have already binged all the episodes released so far. Join us in listening to “Unlocking The Foundation” everywhere you get your podcasts. (SPONSORED)

Digital champion, pioneering researcher, and clinical geneticist, Dr. Charles Shaw-Smith, discusses the impact of digital tools on clinical genetics as well as his experience and insights championing the adoption of digital tools. Hosted by DNA Today's Kira Dineen. Watch the full episode at https://phenotips.com/speaker-series/digital-tools-in-genetics.html (https://phenotips.com/speaker-series/digital-tools-in-genetics.html)

Laura Hercher, host of our sister podcast, The Beagle Has Landed, joins us today to compare notes. Her gig is much more focused on the clinical side of genomics. Genetic counselors are her core audience. Today we do a highlights show looking back over the Beagle's past year.

Dr. Wendy Chung is the Herbert Irving Associate Professor of Pediatrics and Medicine and Director of Clinical Genetics at Columbia University. As a human molecular geneticist, she seeks out rare and unexpected causes behind health problems in people. Her laboratory works to identify genes that cause human diseases and use this information to inform the creation of novel treatments in the future. Wendy spends most of her free time with her family. She has two sons, and they like to get outside to go hiking, swimming, and bicycling. They can also frequently be found working through puzzles and going on mystery scavenger hunts together. She received her undergraduate training at Cornell University and went on to receive her PhD in Molecular Genetics from Rockefeller University and her M.D. from Cornell University. Afterward, Wendy completed her Internship and Residency in Pediatrics, a Fellowship in Clinical Genetics, and a Fellowship in Molecular Genetics at the Columbia Presbyterian Medical Center. Wendy is the recipient of an American Academy of Pediatrics Young Investigator Award, the Charles W. Bohmfalk Award for Distinguished Contributions to Teaching in the Clinical Years, the Medical Achievement Award from Bonei Olam, as well as the Presidential Award for Outstanding Teaching from Columbia University. In our interview, Wendy discusses her journey through life and science.

In this episode of The Rising Tide Podcast, Dr. John Pfeifer of Washington University School of Medicine in St. Louis sits down with the Center for Genomic Interpretation to discuss, among other things, in silico proficiency testing to improve quality and accuracy in clinical genetics and genomics

Mary Willis is a Clinical Geneticist with both a Ph.D. and an M.D. Upon finishing her education 40 years after starting it, Mary began working for the Navy as a clinical geneticist, treating those with inherited disorders or genetic abnormalities, while identifying some new ones along the way. Mary is one of the smartest people I have ever met and it was a pleasure getting my short-minded brain blown so consistently throughout this conversation. Thanks for listening.

In the second episode of The Rising Tide Podcast, Dr. Ali Khaki of Stanford University sits down with the Center for Genomic Interpretation again to discuss the promises and pitfalls of precision medicine, potential consequences when FDA approvals extend beyond populations of patients and clinical trials, how to improve selection of patients for therapy, and concepts that all stakeholders should consider for these complex topics. This particular episode is geared toward anyone seeking detailed, in-depth perspectives about oncology precision therapies. 

In the third episode of The Rising Tide Podcast, Dr. Madhuri Hegde, Perkin-Elmer's Chief Scientific Officer, and co-author on the 2015 "Standards and Guidelines for the Interpretation of Sequence Variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology," sits down with the Center for Genomic Interpretation to discuss past and future guidelines and considerations for variant classification. 

In this first episode of The Rising Tide Podcast, Dr. Ali Khaki of Stanford University sits down with the Center for Genomic Interpretation to discuss FDA approvals in precision medicine and cancer that miss the mark, what the consequences are for such approvals, and paths forward that could drive improvements in quality and accuracy of precision medicine and, ultimately, patient care.

From her TED talks and her appearances on PBS, geneticist Wendy Chung is known to millions of people as an expert on autism. But thanks to funding from the Simons Foundation, she's also known to tens of thousands of people with autism and their families as the leader of history's largest study of the genetics of autism spectrum disorder (ASD). It's called SPARK, for Simons Foundation Powering Autism Research for Knowledge, and it's a big-data exercise of unprecedented proportions.SPARK is partnering with more than 30 medical schools and research centers to recruit 50,000 families with members affected the ASD. Participants have their DNA sequenced, enabling SPARK to build a list of genetic differences linked to autism as a starting point for research on the causes and mechanisms behind the condition. At the moment the list includes 157 single genes and 28 copy number variants. But changes in these known ASD genes show up in only about 10 percent of families studied—suggesting that the existing list is just the tip of the iceberg. Identifying common gene variants with small effects requires large sample sizes, which is why SPARK aims to recruit so many participants. At 50,000, the SPARK researchers think they'll be able to find as many as 150 individuals with mutations in each of the 100 most common ASD genes.SPARK is unusual not just for its scale but for its participant-friendly design. Biospecimens such as saliva samples are mailed in, and patient data is collected through remote online questionnaires rather than in a clinic. The study also follows participants longitudinally, and it returns genetic data to them—an uncommon practice in large studies due to its resource-intensiveness.Chun trained in biochemistry and economics at Cornell, earned a PhD in genetics from Rockefeller University, and got her MD from Cornell University Medical College. On top of her role as SPARK's principal investigator, she is also the  Kennedy Family Professor of Pediatrics and Medicine and Chief of Clinical Genetics at Columbia University Medical Center.  Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:• Launch the “Podcasts” app on your device. If you can't find this app, swipe all the way to the left on your home screen until you're on the Search page. Tap the search field at the top and type in “Podcasts.” Apple's Podcasts app should show up in the search results.• Tap the Podcasts app icon, and after it opens, tap the Search field at the top, or the little magnifying glass icon in the lower right corner.• Type MoneyBall Medicine into the search field and press the Search button.• In the search results, click on the MoneyBall Medicine logo.• On the next page, scroll down until you see the Ratings & Reviews section. Below that, you'll see five purple stars.• Tap the stars to rate the show.• Scroll down a little farther. You'll see a purple link saying “Write a Review.”• On the next screen, you'll see the stars again. You can tap them to leave a rating if you haven't already.• In the Title field, type a summary for your review.• In the Review field, type your review.• When you're finished, click Send.• That's it, you're done. Thanks!Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: From her TED talks and her appearances on PBS, geneticist Wendy Chung is known to millions of people as an expert on autism. But thanks to funding from the Simons Foundation, she's also known to tens of thousands of people with autism and their families as the leader of history's largest study of the genetics of autism spectrum disorder.It's called SPARK, which stands for Simons Foundation Powering Autism Research for Knowledge. The study has enrolled over 100,000 individuals with autism and another 165,000 family members. It's designed not just to advance understanding of autism's causes but to follow people over years or decades and help them lead successful lives.Chung calls it the Framingham of autism, a reference to the famous Framingham heart study that began in 1948 and is still going on today. So, talk about big data! When you're sequencing the exomes, that is, the expressed genes, of a quarter million people, and sharing all of your data back with patients, you're dealing with an unprecedented data management challenge. In fact, SPARK has so much data Chung jokes that she has to compete with Bitcoin farmers to buy new computer servers.But Chung isn't finished. She wants to keep going until SPARK has enrolled 50,000 families altogether. The hope is that with that volume of genetic data, scientists will be able to to figure out which genetic variants that contribute to autism might be amenable to treatment with new drugs molecules. And because the SPARK study is also collecting data about the lives of people with autism as they grow up and encounter all of life's challenges, Chung hopes the project will be able to provide individuals on the ASD spectrum with coaching and other forms of support.A few weeks back Wendy made time to talk with me about all that. And now here's our conversation.Harry Glorikian: Dr. Chung, welcome to the show. Wendy Chung: Thank you for having me today. Harry Glorikian: So I feel like I almost know you from watching you on PBS and watching you interact with your patients. So you'll forgive me if I'm more comfortable than, than actually meeting you for the first time face to face.Or I should say virtually, I think we've been doing this too long now. But, you know, I know we're going to talk a lot about your program SPARK today. But I'd like to sort of start with a little bit of maybe of history and some background, you know, it seems like one big question that attracts you above all.Others is the genetic basis of human disease. And so how did you first get interested in that?Wendy Chung: All right, so I'll go way, way back. I think I've always known that I wanted to go into science and medicine and tried to figure out a way to put things together. And for me, I guess the moment, and you'll be able to calculate my age from this.But the year that I started, my MD-PhD training program was the year the announcement was made that we would start the human genome project. And I knew I already had a passion. For what we call inborn errors of metabolism or metabolic diseases, but it became very clear to me that we would have insight into the genes and the genome to treat conditions like that.Plus other ones as well. And an MD-PhD program takes a long time to finish your entire training going to graduate school and medical school and residency and fellowship and all of those things. And so you could project out. that it might be as long as 15 years before I would finish my training.And if you looked at the projections for how long it would take to finish the genome, they basically converged about the same time. And I'm one of these people. I like to think that I'm a strategic planner and visionary. I don't want to sound egotistical on this, but I am a planner. And as I started planning, I thought to myself, well, this is really going to be incredible.The power that we'll have as a scientific and medical community. And this whole job description doesn't exist. You know, so we are gonna need people to be essentially, genomicist a brand new field of both science and medicine. And I kinda like puzzles. I like logic and I like having definitive answers.And that's what I think the genetics often provides us. And so it's really with the excitement of the opportunities with a brand new field along with just. The way my mind works, that this was really perfect. And, and I was lucky. I have to admit to be able to discover that early in my career. So what I start out to do almost the first day of medical school has really been what I've continued to do for my entire career.So, anyway, Harry Glorikian: well that is that's, that's incredibly lucky. I mean, I do believe in a process and a plan. I can't say that at a young age, like you, I knew exactly what I was going to do when I grew up. It seems to be in the same area of, of. Biology, but I think that's the only common theme that I would say. So this program SPARK grew out of the existing Simmons foundation called SAFARI right?The Simmons foundation, autism research initiative. You were on the board of SAFARI for a long time. And then, and then you became a program director of clinical research. Can you talk about. Why you felt drawn deeper and deeper into specifically autism research? Wendy Chung: Sure. So I'm trained as a pediatrician and a medical geneticist and a fair number of the patients that I see.And this was true for pre-existing before SAFARI or SPARK ever came along. But a lot of my patients have neurodevelopmental conditions and or autism. So it's a common reason for people coming to see us over my career. A lot has changed in terms of our ability to understand the underlying etiology, especially with the genetic etiology.And I will give credit that was in large part due to the SAFARI program at the Simons foundation, they really did have this original vision in terms of, we needed to understand the brain and behavior across for individuals across the spectrum. And that a really. Powerful tool to do that would be genetics.It's not all genetics. I want to be clear about that. And it's a wide spectrum. But I got pulled in just because of my expertise as a geneticists to advise the SAFARI program. And as you said it started out as advice and due to. Individuals who were there and got to know me and thought I might be able to contribute.in even bigger ways got sort of pulled from the outside to the inside, so to speak. And as that happened and understanding what the gaps were SPARK or Simons Foundation powering autism research for knowledge is the acronym. That was a vision realizing that to really make the. It's scientific inroads, we needed to do.We needed to think big. And that's because autism is not one condition. It's quite heterogeneous. It's quite complicated in terms of etiologies. And we really need to base, we need to have hard foundations, really solid evidence to be able to know what direction to go with the science and that genetics provides that solid foundation.Harry Glorikian: Yeah. I'd say it's, you know, I've I was trying to get ready for this. And I was trying to do as much reading as I could. And I realized like, We know, we know some things, but there's a lot we don't know. And then there's certain things that seem to trigger it and we're not, we don't fully understand what all those things.It's a very interesting sort of set of reading that I went through very quickly. So I'm probably like a millimeter deep and pretty wide compared to you. But it is interesting how. Genomics and genetics have, are really driving a lot of areas that we see right now. It's funny because I remember when someone way back in the beginning, so I'm dating myself also.It was said, why would you sequence anything? And now it's like, we, we want to sequence everything. And the information that it's giving us. So can you give us a high level explanation of what SPARK is and. How different it is from some of the previous studies of autism spectrum disorder and in terms of scale and goals.And, and when did you decide and how did you decide to embark on this? Cause it's I was reading this study. I mean, it is, it's a pretty ambitious goal. Wendy Chung: So again, At the Simons Foundation we had started out with something called the Simon simplex collection. And I think of that as sort of the first foray into the genomics, that was to give you a sense of order of magnitude about 2,500 individuals with autism.So, you know, a big, big order, you know, 20 fold difference in terms of the original goals, at least for SPARK But that was, I think of as being very careful in terms of making sure the individuals within that Simon simplex collection, they went through very extensive in-person evaluations with masterful clinicians, psychologists to make sure the diagnosis was unambiguous and then had the genomics sort of layered on top of that.And I won't get into the specifics of cost per person to run through that, but that was really, I think, of as the platinum version. And that was important for the field. To be able to have that again as a solid foundation and to be able to make some statistical arguments about what sample size did you need to be able to get to understand the entire complexity of autism.So it was definitely foundational and necessary. But in terms of being able to do that with about 2,500 individuals, you could make estimates, right? But in terms of the number of genes that would be involved in autism, it would be around the order of 500. And so that's just for, you know, a certain portion of the spectrum as well.And you can understand therefore, the complexity in terms of what we're talking about. And, and I'm just because I know there are some people who may not understand exactly what I'm talking about. Let me just be a little bit more granular. For people who come in to see me with a child with autism example, I'll have some individuals who may be non-verbal.They, they will never be verbal. That is they'll never talk. They may be able to communicate in some way, but they may be intellectually disabled. They may have. Seizures or epilepsy. They may have even medical problems associated with that. And that's one portion of the spectrum to another portion of the spectrum are individuals who are just incredible in that their mind works differently.It doesn't necessarily work in a wrong way. It just works differently. And they see the world in a different way. And oftentimes I have to say are profoundly insightful in terms of. Problem solving because they do come at it from a different direction and they do have just fresh eyes to be able to look at complex problems.So, and again, I, I want to be very clear in terms of how I'm talking about this. I don't consider autism a disease in that way. It's a difference, right. In terms of all of what we're talking about. And I want to be very clear also in terms of the genetics. Yeah. That this is not to get rid of anyone. This is not to be able to have a eugenics movement where we're trying to eliminate individuals with autism.It has nothing at all to do with that. It really has to do with understanding the underlying biology of how the brain works, because we've really been so much in the dark that people had theories and hypotheses, and they'd waste a lot of energy doing the wrong science because it wasn't based on that foundation of really.Truth with a capital T what are the molecules in the brain? What are the different parts of the brain that are involved? How does it change over time? We really needed that foundational information to go from kind of the dark ages of autism research into the modern age and era. And so in doing so that's the Simon simplex collection found, you know, allowed us to see what sample size did we need.So we started doing some rigorous statistical calculations of how many we'd need to get to that goal of having maybe not every single gene, but the majority of genes. And that's where the calculation of having 50,000 families. originally came up. And so that was our original goal to be able to scale that you know, 20 fold higher than what we'd done with Simon simplex collection.But if you started looking at number one who was able to participate, like who literally could give up a couple of days of their life to go in for these evaluations who was close enough to one of these study centers to do it it, it was. Partially an equity issue for me that I wanted to make sure everyone could get access to be part of understanding better and to be represented, because if you're not represented, your voice may not be heard in terms of the research.So part of it was from that point of view is from a convenience point of view making sure that individuals wherever in the United States, if they wanted to be in their pajamas at 11 o'clock at night, to be able to do this, they could do it. Then, and it wasn't so burdensome. So the whole process, you know, it takes maybe an hour or so to be able to register and become part of this, not to say that you can't do more than that first hour, but to start this off, it becomes easier.So it was with that and, you know, we've had, in terms of timing, we've had lots of ability to do things online that we couldn't do before. So when we first started this, you know, the internet wasn't as evolved as it is, and there's just a lot more we can do from home. And in general, one of the parts about SPARK that I think is really important is.That it's meant to capture people where they are. And so, I mean that both in terms of just the convenience of participating, I also mean in terms of behaviors. And so, again, as a clinician, I have children with autism who come into my office, who I have to admit it's a terrible experience for them. They're petrified in terms of, you know, they like it.They liked to understand what's coming. They don't like surprises. They get anxious. Being out of their elements is really hard for them. And so being able to do things where they're on their home turf, they're on their home territory and being able to capture behaviors where they really are rather than our artificial environments of being at a laboratory at a university at a hospital.All I think is really important to truly see what life is like for individuals. So we're trying to do all of those things in terms of really capturing, you know, more of accurate information, more data. So in terms of doing this, not just the one time you can come in and be evaluated, but over your life course.And so that's one of the things about SPARK is this is not a one and done type of. Snapshot of who you are. This is really thinking about a life course. And I really, I want to emphasize this. One of the other things about SPARK is not just the number of individuals, but it's the longevity of what we're planning to do.We've, we're celebrating our fifth anniversary this year. And from my point of view, we're planning on going this for a lot, lot longer. I don't know if it's going to be 50 years. I don't know if I'll last for myself for 50 years. But but, but this is, I tell people who will understand what I mean, this is meant to be kind of like the Framingham of autism.Another words, you know, being able to really see people through different changes over their life course, different stages of life, different challenges, trajectories of how things evolve and importantly, what we can do to change that trajectory potentially or support people better. So that sometimes when people fall through the cracks with young adults, especially is one area that I'm mindful of.How do we prop them up? How do we make sure that transition is easier? And so, like I said, for anyone, wherever they are on the spectrum, I think there's always some time, some place in your life where you need an extra helping hand. And so I hope this will start to provide that evidence base for where we can provide that helping hand and have the greatest potential impact.Harry Glorikian: Yeah, no, it's, it's this term we're using autism is, is, is quite captures a very broad set of. People as, as you indicated, like, you know, you know, Elon Musk recently got up on SNL. Right. And you had to know that he was a little off anyway before that, but, you know, I actually believe that people like that can see the world in a certain light, through a certain lens that a lot of other people would be like, I have no idea what you're talking about.I can't see it. So. All of these people, right on one spectrum or the other, which I think all of them add value as, as they're going through their lives. But the other interesting part of this study is you guys are sharing the results with participants, right. Which is not usual and not, I don't think trivial to do.So. You've got a unprecedented level of engagement and data returned to individuals and their families. You're not just returning genetic data, but aggregate reports, which in accessible language, which, you know, I'm trying to re I just finished my third book, trying to write it more accessible, of our world and I can tell you that was truly challenging.So I, what was the philosophy behind that? And what are your challenges around trying to do that?Wendy Chung: Right. So you're, you're absolutely right. I, I think in a very good way, we've been from the very beginning, and even in the planning stages of this had participants as part of that planning process and they still are literally on our staff on everything that we do, they are integrated on our teams.So let me paint a picture for you. About some of the details of what you're talking about. So as of this morning, as an example, we have over a hundred thousand individuals with autism in SPARK. We have over 265,000 total participants. So the reason why the difference for those is some of those are.Parents for instance of individuals with autism or siblings because we do encourage families to participate. So you can see that this is massive, right? This is over a quarter of a million people that we're trying to be able to in some way, juggle with all of this. And so for me, that was, you know, I don't unlike.Most of my other research studies. I don't personally know every single person in the study. I never will, unfortunately, but we do have anchors of 31 clinical sites around the country. So that's one of the things that we do to make sure that we have our finger on the pulse in some way of our participants.But I will also admit you could just be, like I said, in your jammies at 11 o'clock at night tonight and Google SPARK for autism and be able to find and sign up for this, you know, there's no, you don't have to be at one of these sites to do this. You're right. That the philosophy I heard from our participants from the very beginning, and some people may have heard this term is nothing about us without us.And so in terms of research, the idea that we want to be as research participants, we want to be part of the research team. We want to be able to have a voice we want to help you do your job better as researchers. So, you know, it's not just in a selfish way. It's about, what's going to really make us committed to doing this, not as a one and done study, but as the picture I painted to be able to continue to participate for decades forward. And so in hearing that then in hearing what was important to participants, keeping in mind that I can't do everything for everyone, you know, we have to have compromises in this. It became important for people to have access to their genetic information.But not just like, give me a flash drive with my raw data. Right. That's not helpful. If you're interpreting this information to understand genetic causes of autism and you find that for me, let me know about that. And in addition, and I, I am proud of the way we did this. We did this, not with just sort of sending someone, an email and sending, okay, well, guess what, you've got to SHANK3 variant, and this is the cause of your autism.We do this. And I think about this for myself, what would I want to do for me? What would I want to do for my family? If this were my son, how would I want this done? If I weren't a geneticist? And so we've built in I call it, choose your own adventure, but we give people choice in the sense that. When we return, number one, it costs no one, anything.Let me be very clear about that. So it's not like you're buying a test or anything. If anything, we will not. If anything, we do give you a token of a gift certificate to thank you for your time, because we know it takes time to be able to do this, but we pay for everything with this. And so we do it.For those that are aficionados. We do a process called exome sequencing to be able to look at comprehensively across the genome as we do this. And it's about right now as of today, about 10% of our participants, where we find something that we can be pretty certain is the cause of the autism in the family.And we. Again, pay for this ourselves to have a second group of people. Double check, make sure it's correct. And then the choose your own adventure is either you can choose to have your own doctor to give you that information back and explain it to you. Or if you don't feel like your doctor is the best person to do it, because maybe they're not a geneticist, maybe they don't have any idea what we're talking about.We pay for the study centrally to have a trained set of genetic counselors, be able to return the information. And I, and my team have personally written out what we call brochures in. As you were talking about lay person language that describe each one of the over a hundred conditions that we now return.And so it was a lot of work to write each one of those brochures for each one of those conditions. And to keep them up to date, but. That's how committed we are to this community. That's how important I think it is. Harry Glorikian: I, I almost feel like I need to sit down. That's just the enormity of that task is, is is extremely commendable.I can't believe I'm getting a commercial enterprise like to do that. Right. Is, is not trivial. So. That's that's incredible. Wendy Chung: This is like the Ginsu knife set, but wait, there's more! So we also appreciate that not everyone is going to have a genetic result. And so we also have parents for instance, that are completing questionnaires that tell us about how their child is doing in terms of behaviors or you know, things that are related to autism or behavioral issues.And I have to say during COVID as well, Especially, this was a big issue for many people, not just individuals with autism but about psychological differences and making adjustments during COVID. So within that we give and these are again, standard psychometric tests that are used so-called in the industry.So in other words, by psychologists who are practicing we give that information back to families. We use infographics. And so all of this has been test driven in plain language with groups of individuals that are average parents, individuals with autism. We have a commendable group of about 80 of our participants that sit on our board again, giving us feedback before we go live with any of this, telling us how to tweak it, to make this more accessible, using different infographics, to be able to make this easy.But every one of those things that we can return, then. We return it to our participants. We have something called a research match program. So we have over 150 researchers who use SPARK as a way of letting the community know about the research they're doing and being able to match SPARK participants with research so that this is, as you can see, it continues to kind of organically grow, not just SPARK, but the entire research community.And a requirement for every one of those researchers is that when they complete their research, they have to actually give that information back to the people who participated in the research, into the SPARK community, in lay language. So in a way that families and individuals. Can access and understand it.And we have many of them give webinars or be featured in our newsletter, but the whole process is we're learning together. And I want, I want people to see how science is done. I want them to be part of like the front lines. Like they're getting the preview in terms of hot off the presses information.So with this, hopefully this is a movement in science. It's not just SPARK. I hope all, all people do this. Harry Glorikian: I was going to say, I think you need to teach a master class on how to do this because. I'm not familiar. Maybe somebody else is doing it, but I'm not familiar with it. Usually I get gobbledygook back.I mean, I just actually volunteered to do a diagnostic clinical trial and it was, and I'm in the, in the business and I was reading what they wanted and I was like, I don't understand this at all. I don't understand what you want from me. I don't understand what I'm going to get back. I don't understand anything.I'm not participating. I don't have time for this. So but all the stuff you said now really rings in my head of A), a data management challenge, B), analytics challenge, and C), how do you automate some of this? Because the first thing that goes into my head is is there, you know, some aspect of AI or machine learning that can do some of this because.If I'm not mistaken, every time you discover more variants, you're going back and reanalyzing the genomic data. And that becomes exponentially a bigger and bigger task. If there isn't some level of automation to sort of make part of that more turnkey. So what are you doing there? Wendy Chung: Yep. So you're absolutely right about you know, we have thought about ways to scale.This scale is one of my favorite words right now. Because you're right, that each time we get more people that come in and more data, we turn, we, you know, turn the crank. One more time. Knowledge is increasing around us about the brain and behavior. We're adding that and putting that back in, and then again, increasing the robustness of what we do.And we do want to be really rigorous in terms of as we're doing this. So that's on the genetic side. And so there are. Our ways of being able to do that, I will say it takes more and more in terms of computing time or sort of, you know, person power to do this Bitcoin, by the way has been a problem.They're buying a lot of servers. They need to, you know, free up some of those for science anyway. But aside from that there's also the issue in terms of people report to us behaviors and in an interesting way. And it's just kind of what happens when you do science this way. Not everyone is perfect in terms of how they.Decide to participate and I get that. And so what I mean by that is there's missing ness of data that we as researchers have, you know, we realized that we've used the machine learning and some ways to fill in those missing pieces. And so what we've tried to do is use machine learning. I talked about a spectrum for instance, and people are at different ends of the spectrum that ends up being incredibly important to interpret the genomic information, as well as information about other people in the family.And yeah. How their genetics go with their own particular place on the spectrum. And so putting all that together, we can get a profile with machine learning, to fill in some of the gaps, fill in some of the blanks, understand issues with trajectory, and then combine that with the genetics. And so the good thing, and this is another reason why we set up SPARK the way it is.I'll be very clear to anyone who's thinking about this, either as a contributor, as a user. Everything is de-identified of course. So no one knows who any participant is, but I, I set this up originally so that the broad research community would be able to think about these problems. And I tried to de-risk it for any scientists who wanted to enter this.So as a data scientist, for instance, You may not be an expert in autism, but I want you to be able to contribute in terms of doing this. And so the way this is set up again is the entry to access this as you do. We make sure you're a real bonafide researcher. We do go through a rigorous check of that, but you don't have to be an autism researcher.You could be in industry, you could be an academia, you know, you could be at a private foundation. We just want to make sure you're doing good science. And I have been saying that many of the people who are using the data. are not necessarily, they didn't start out as autism researchers. They simply are data scientists, computational biologists, who are able to look at the data in interesting ways.And I think the more we can bring smart people to the table on this, the faster we'll get some of the answers we need. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian: Did you ever think when you were getting your MD-PhD that you'd have to become a data scientist or an IT manager? Wendy Chung: So not exactly. And in fact, so anyway, I'll tell you sort of how I grew up. I was actually as growing up, if you had asked me what my natural proclivity or skill was, I was definitely mathematically inclined.It was very data science inclined, very mathematically inclined. And. Probably even too good in some ways for my own shoes. Cause I kind of got ahead of myself in terms of taking very advanced courses at an early age it was, I'll never forget this conversation though. I had a discussion with my math professor as an undergraduate and said, you know, I'm really good at this stuff, but what can I do with a degree in math?And he said, oh, well you can go work at an insurance company. You can be an actuary. You can. You can figure out what rates, you know, people should be paying in terms of their insurance. And I said, Really that's what you do with a math degree. And like, literally I did a 180 pivot and said, that's not worth, you know, going into for that.And that was, I have to admit unfortunate and, and, you know, I, I'm not saying everything happens for a reason. I have no regrets in terms of what I've done with my life. I think that, you know, I found my home and, you know, a great thing to do. But I do have some regrets that, you know, He had that influence on me in that way.So, you know, I could've seen myself the time when I grew up, you know, we were just starting to have personal computers, you know, we were, we didn't even have emails or internet or, you know, it's a completely different world than when I was training. So I will admit. That a lot of what I do is done by others.I think that's a good thing. I will say team science is incredibly important. And even though I'm here talking to you today, really I'm representing literally hundreds of scientists behind the teams that are actually doing the hard work, whether it's coding, to be able to make our interfaces for users valuable, whether it's data scientists analyzing the data, psychologists neurobiologists, you know, there are just amazing people that are behind the scenes doing all of this.And so when it comes to a lot of the really heavy lifting. I will admit that they're the ones doing the heavy lifting and, you know, in a good way, I think I've got the vision to guide the ship. But there are a lot of really smart, especially young minds that are driving a lot of the science. Harry Glorikian: So I want to switch here and switch to recruitment here just for a minute or so, because I also want to ask some of the listeners to point people in, in the direction of this study.Right. Dump more people the better, but W w where are you now from a numbers perspective? The last numbers that I saw were. 18,000 individuals in 2017 and 28,000 family members on top of that, I'm sure it's grown since then, but w what are the numbers right now? Wendy Chung: Yep. So, as I was saying, you know, the numbers are in terms of people registered just over a hundred thousand with autism and just over, it's about 265,000 total.So I'm not gonna. Anyway, I'll I'll go ahead and just say it. So there are individuals who get stuck at various different stages in the process. I will say, dads seem to get stuck more than moms do, and I can understand dads are busy. But when I, some of the numbers you were quoting, for instance, we have registration.We also have send out a saliva kit for people to be able to donate a DNA sample. So they spit in a tube and they send that back. And so we have a fair number of people that get stuck at that point and dads in particular. Yeah. When we started out the sequencing, one of the things that I'll just give a little science behind this is that we call them Denovo genetic variants.So variants that are brand new in the individual with autism are oftentimes some of that 10% that we'll recognize as a cause of autism. I'm not saying those are the only causes, but those are the ones we recognize at this point. So it became a, and has always been really critical to have both mother and father and the individual with autism whenever possible, so that we.You could very quickly recognize what was different in the child with autism, from either their mother or father, having them in comparison, just like makes that sort of crank we were turning about very easy to turn. We've had issues in terms of being able to get, and I call it, we call them dangling dads.But dads that, you know, just haven't quite gotten it together and have found the time or found their kit to send that back in. And that has decreased the number of family units, mothers, fathers, and children with autism that we can look at. And so. has limited. Some of the analysis that we do on the other hand, as I said, we want to make sure everyone that contributes is able to contribute.So we have our analyses now include every single person who's contributed a saliva sample to SPARK, at least a, you know, saliva sample that's been sufficient to be able to sequence. So whether it's just one person or one person in their mother or one person and their father, everyone is represented in what SPARK does.Just a question, as I said, of what we can recognize I do want to call out and this may or may not be obvious to listeners, but I do want to call out. It is really important for everyone to be represented because of the number of types of autisms. But also I think it's an equity issue in terms of ancestral diversity.So where in the world. Your family came from, if they came from China, if they came from Brazil, if they came from Ghana, wherever in the world, they came from, it's really important because the genetic variants from our ancestors differ depending on where in the world you came from. And right now, in terms of genetics, about 80% of the genetic data we have as part of research comes from individuals from about 20% of the world's population.And so we are. Overrepresented for individuals of European ancestry, which means that in terms of being able to recognize those genetic factors, we do a pretty good job. If you're of European ancestry, we don't do nearly as good a job, though. If your family comes from other parts of the world and. Both in terms of equity and making sure that we don't increase this gap in terms of genomic medicine and utility of this information.It's really important to me that everyone gets the same shot at this. And that's part of, like I said, why we made this so easy for people. And I hope they'll take advantage of that because some people won't get this information any other way,Harry Glorikian: We need to be inclusive of everybody, but when I look at the trajectory and the, and the.How all of these technologies across a number of different areas, that seems to be a common theme is, you know, who accessed it first? Where do we have the most data and what do we need to do next? And I, I look at the, all these technologies as on an evolutionary scale, right? Where, where we're, we're continuing to add and how do we get to more people?How do we make it easier for people to participate, et cetera? Cause. When we were at applied Biosystems and there were sequencers right there. I mean, you could just, it was pretty easy to participate. Whereas for other people who don't have access or it's not as, I mean, if D'Souza at Illumina does what he wants to where he's, he's talking about a $60, whole genome.There'll be things that we'll be doing that we haven't even thought of yet. Wendy Chung: Absolutely. And we've thought of some of those things. So the next time you have me on, we'll talk about some of those others. But, but I, you know, in So, although there's the accessibility, I do think there are some issues, understandable issues about trust.And do I want you to have my genome? Do I trust you to have my genome? You know, could you do something Is some police officer going to arrest me or, you know, try and somehow plant evidence. That's going to be used against me in some way. So I think there are all sorts of reasons why certain members of our community don't feel comfortable with them.Participating and I totally get that. I think part of it is I want to make it easy for people. I also want to make sure and it's through SPARK that we're doing, this is to understand and have those individuals have a seat at the table, be able to address as many of those concerns as we have. So we can build that trust and build that, you know, shared vision and shared goal in terms of moving the science forward.And I say this and it's slightly different. I'm going to slightly digress, but I also, as a geneticist, for instance Treat patients for instance, who have cancer or have a family history of cancer. And I'll just very briefly share a story, which is that I had a patient who happened to be of African-American ancestry.And she actually through a very long I'll just long story short had a family history of breast and ovarian cancer. And although she did the sort of BRCA tests that some people talk about BRCA1 and 2, she did not really get the full. Understanding of the information from that test because she had a genetic variant that at the time wasn't recognized it happened to be a real true, what we call disease causing variant to increase the risk of breast and ovarian cancer.But it wasn't recognized because her community, her individuals from the same ancestry, weren't represented to be able to distinguish sort of the signal from the noise if you will. And so that's what happens in terms of, and she ultimately went on to develop. Metastatic cancer, unfortunately. And so there's this gap that has been evolving and actually gets wider and wider with the more that we depend on using genomic medicine, either to select the right medication or be able to decide what preventative treatments or what increased screening to do.There becomes a wider and wider gap between the haves and the have-nots. And I, I just want to make sure we narrow that gap. We get back to being equitable. Harry Glorikian: I totally agree. I mean, I have my own pet peeve stories about BRCA I mean, I was lucky enough to do I helped Myriad with some of their strategies and, you know and I got to learn a lot about their database versus everybody else's database.And so I have my pet peeves on where people should go and get their testing. But I also agree that being able to explain this to someone. Is not trivial. That person didn't fall off the turnip truck. Right. And the data is changing daily. I used to be able to turn on my computer and I'd be like, oh, I can keep track of that one and keep track of it.Now it's for forget it. If I don't have IT support. Hmm. And somebody who's been studying it it's, I don't want to say it's relatively impossible, but it's extremely daunting. To sort of keep up with what's going on. Wendy Chung: So let me just I'm going to stay on that note, although it's not directly SPARK related.There's some listener out there who would this'll resonate with your point of scalability and to be able to wrangle all of that changing interpretation of the data in real time is very important to me because like you said, there's a lot that we don't yet know what it means, not just related to autism, but related to a lot of the way our bodies function.And there needs to be a platform and informatics system that facilitates that you as an individual to your doctor would be great. But you also, as an individual can contribute to and engage in to be able to manage your own health. Harry Glorikian: So I have to tell you, I mean, after all the work I've done and everything that I've tried to write and so on and so forth, this whole idea that everybody has, that they're going to have their individual silos is to me, a bunch of malarkey, right?We've all seen that when you put all the mapping information and Google has it, it's an exquisite piece of, you know, useful database that you get you around tells you where you need to go, what you need to do. It's not. there aren't 50 of them or a hundred of them. I mean, in our world, if I think of everybody's individual silos, there's thousands of them.And it should be, I mean, the country itself needs to aggregate this. I know that medical professionals will be like, no, it's my data. It's not your data. It's the patient's data. And it should be aggregated. And by aggregation, we can gain more insight into it, but, you know, These are policy issues that every once in a while, I try to influence people on.But boy, they, they, the technology is moving much faster than the understanding of the people that are writing the policy and not to digress. But I think if we want to solve problems or at least gain a deeper understanding until we do that, I think it's just going to be chipping away except for programs like yours or certain companies that I know that are spending the money to.Build a massive data set that they can then sift through. But all of this work that you're doing is to diagnose the patient better, manage the patient, better, understand the progression of PA of the patient, but it's also to eventually I'm assuming design certain drugs or, or certain therapeutic interventions that, that, that w w where are you from?In that standpoint. Wendy Chung: Yep. So we are moving forward. It's not going to happen overnight, but I talk a lot about getting people to the starting line. So we have a sister study for SPARK called Simon Searchlight. That's actually, we've been doing that for about 10 years. That now is once you get a diagnosis, a genetic diagnosis, the point is then you've got a group of individuals that all share that same genetic diagnosis.You can learn from each other. You can learn from researchers. And to your point now, you know what starting line and what race you need to line up for. Right? Because you're in terms of a treatment or a support, it's likely to be specific. There may be some commonalities across genes, but in some cases, if you think about a gene therapy or gene editing or gene replacement or something like that, That is going to be at the level of specificity, at least at the gene.And in some cases, maybe even by the genetic variant. So in terms of doing that number one is that I do think this is going to be, I call it a step function mathematically, right? So there are going to be enabling technologies. And when certain enabling technologies and delivery systems are in place, they're going to be, it's not just going to be one condition.That's now treatable. It's going to be a whole class genetically of conditions that are treatable. And it's a matter of as modules popping in the right gene into that system and making sure that the window of opportunity for treatment is still open. But as we're doing that, it's important to me that even for conditions that are seemingly very rare, they're in the aggregate.Quite common. And there are a lot of lessons to be learned from each other as we're doing that. So it's kind of getting everyone lined up. We're starting to think about, and I don't want to put a timeframe on it, but it may be as soon as within the next year or two, that we'll be starting to actually use treatments.In some of the individuals, either in SPARK or Simon Searchlight with one of those genetic events that's amenable to some of these molecular technologies. We have a clinical trial for something called R-Baclofen that got shut down by COVID, but hopefully we'll be opening up again soon. And that will be it's a small molecule or a pill that you'll take.But for certain individuals with a particular group called 16P11.2 deletions, again, one genetically defined group. But that clinical trial, I hope will be opening up in later in 2021. So we are marching forward towards treatments. We also think of, as I said, supports for individuals.So it's not just about changing the person or giving them a drug. But thinking about, you know, what do you need? Is it that you need coaching in terms of how to, you know, ask someone out on a date, how to be able to interview for a job, how to, you know, be able to get your life together, to go off to college and live somewhat independently, you know, Things like that, that may be a little bit more difficult for certain individuals.But how do we deal with some of those things as well? All of these I think are going to be incredible opportunities. And like I said, a large part of what I do is try and de-risk all of this. So think about the research community. What does the research community need? What are we going to need for FDA registration?How can I make this easier, more accessible? Like how can I. What are the tools I can put in the toolkit so that if someone has got a hammer, I can point them to all of these nails out here that they can just start hammering one by one and be able to hopefully make a much bigger impact than they could if they just, you know, saw one nail that they could hit.But with this, like I said, it's not going to happen overnight. It's still, I think, you know, when I think back to the last year of what we've had in terms of molecular therapies, you know, things like Spinraza and spinal muscular atrophy have been truly revolutionized you know, what used to be for me, the most common genetic cause of death for infants is now something that we do with.Newborn screening and we have a one and done gene therapy. I mean, it's just remarkable. I, I never, in my wildest dreams 20 years ago would have thought that we would be there. And I think that's part of the, you know, that sort of vision, that way of thinking about things I wonder and hope that at some point in the not too distant future, we'll be able to identify kids.Early at a window of opportunity for treatment line them up for the right safe treatment, if they needed and be able to bend that curve, put them on a different trajectory than they might otherwise have been on. Harry Glorikian: I've spent time you know, talking to Robert Green about BabySeq and sequencing, you know, children and, and you're right.I mean, if I think about from the day we were starting the genome project to now We we've revolutionized some areas. I mean, things that were a death sentence or whatever have completely changed. I'm not sure the public or people fully appreciate that. That's why, when somebody writes a paper, the genomic sequencing hasn't had an impact.I, it just drives me nuts. Okay we've talked about the benefits of all this, but if you could say to. Why should people donate their genetic data? I want to want to see if we can get some of the listeners to touch some of the people that they know or at least get the word out.And then what, what can the rest of us do to help? Sure. Wendy Chung: So, so if you'd like to participate, the website is sparkforautism.org, sparkforautism.org, right there on that website, on that landing page, you just, there's a tab that says join us today. And that starts you on the process of being able to sign up for doing this.You can share that with a friend. Everyone in the United States is welcome who has we call it a professional diagnosis of autism. So in other words, a psychologist a doctor you know someone has officially said that they have autism, not just that. They think it's a possibility, but someone has really said that they do have autism and of any age.So it could be a two year old to a 50 year old. And then as I said, their family members, so that's in terms of doing it in terms of, like I said, the information that you get back from it, I do hope. This, this, I will say also as a practicing geneticist, this doesn't replace me in terms of wearing my hat as a doctor providing genetic information.So if you're a pregnant mom out there who has a son with autism, and you're worried about, you know, the risks to your baby right now see a medical doctor about this because it takes us a little while on the research side, I won't be able to get you a result a week later, it does take time. So, so we're not meaning to replace the medical system.But as you're doing this, I do hope you'll find it helpful. Like I said, to get some of your own personal information genetically about autism, and most importantly, it's to be represented that is that I don't know where the insight is going to come from. And I want to make sure that we have information that's useful to us.Everyone across the spectrum, whether it be by age, whether it be by gender, whether it be by where you live in the United States, whether it be by your gene. There's so many different dimensions and it changes over the life course that it's a big ask. I realize. But we are committed to doing this and I will say it's through the generosity of the Simons family and the Simons Foundationthat we're committed to this for the long run. I don't have to worry about will NIH fund this for another five-year cycle. I don't have to worry about the upturn or the downturn of the economy or fundraising for this year. This is one of the truths in life that I can say this is going to be around for the longterm.And so you don't have to worry that this is going to disappear or go down in flames or that, you know, your samples and your information are going to be stuck in a freezer or warehouse. And no one's going to pay attention to this. This is, and I've emphasized this, but. This is what's driving autism research in the United States.There are literally hundreds of researchers that are using this as the way to know better. And if you want to be easily in touch with those researchers, find the cutting edge information. This is an easy way to become an insider. So I hope you'll use the opportunity in whatever way suits you best, but definitely share it with a friend and hopefully you'll be able to get something out of this too.Harry Glorikian: No, this is, this is fascinating. I'm, I'm really glad that we have the opportunity to talk and expose the listeners to this because I think what you're doing as a process needs to be replicated in a number of different areas. And then at some point it would be interesting to have a portal that would potentially share and aggregate that information in a, in a way But I, cause I always think, you know, we just don't know what we don't know yet and there's gotta be a way to evolve this as it goes forward.So it was great to talk to you. As I said, I feel like I know you from the PBS show, but great to actually meet you in person and look forward to publishing the episode and, and, you know, getting people excited about this opportunity.Wendy Chung: Well, thanks for having me and helping to increase the awareness and thanks for what you do educating the public about what science and big data are about is so incredible to educate all of us so that we can make better decisions.Harry Glorikian: Excellent. Thank you.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

Genetic testing is on the cusp of a major revolution, which has the potential to shift not just how we understand our risk for disease, but how we practice healthcare. In the clinic today, genetic testing is used only in cases where we know that mutations have big impact on physiology (BRCA mutations in breast cancer, for example). But our knowledge of how our genetics influences our risk for disease has evolved, and we now know that many (tens of thousands to even millions) small changes in our genes, each of which individually has a tiny effect, combine to influence our risk profile. This new appreciation — coupled with powerful statistical methods and massive datasets — has fueled the creation of a new tool to quantify the risk of a broad range of common diseases: the polygenic risk score. On this episode, which originally aired on January 18, 2021, host Lauren Richardson (@lr_bio) is joined by Peter Donnelly, (@genemodeller Professor of Statistical Science at the University of Oxford and the CEO of Genomics PLC,) and Vineeta Agarwala, (@vintweeta physician-scientist and general partner at a16z), to discuss these scores and how they can reshape healthcare, away from a paradigm of treating illness and towards prevention and maintenance of health. 

Professor Sir John Burn is Professor of Clinical Genetics at Newcastle University, a Non-Executive Director of NHS England and Vice Chairman of QuantumDx. His story is fascinating and slightly unusual — because he began life from humble beginnings in a small village in the North East of England. We talk about meritocracy, how to be a showman and why business and clinical academia are really very similar. I hope you enjoy. You can find me on Twitter @MustafaSultan and subscribe to my newsletter on www.musty.io

Pompe disease is a rare, inherited disorder that causes permanent muscle damage in children and adults. It occurs in about one in every 40,000 people, and can go undiagnosed for years. In conjunction with this year's International Pompe Day on 15 April, Dr George Lee joins us in shining a spotlight on this rare disease. We speak to Dr Ngu Lock Hock, Consultant Paediatrician specialising in Clinical Genetics, as well as Sivasangaran Kumaran, father of 4-year old Swathi, who lives with Pompe disease. Image source: International Pompe Association

Richard ROSENQUIST BRANDELL, Professor of Clinical Genetics at Karolinska Institutet, Senior Physician in Clinical Genetics at Karolinska University Hospital, Director Genomic Medicine Sweden Initiative, Stockholm, SWEDEN speaks on "Deciphering the molecular landscape in chronic lymphocytic leukemia: clinical and biological impact". This seminar has been recorded by ICGEB Trieste.

I speak with a friend and colleague of mine with whom I worked in Yorkhill.  He is now a Professor of Clinical Genetics at the MRC Genetics Unit in Edinburgh and has devoted his life and career to understanding the genetic and metabolic basis of severe developmental disorders.  In particular he is fascinated by the concept of genetic disease that is not inherited.  We talk through his career and some of the important discoveries that he and colleagues have made which radically advance our understanding of severe developmental disorders.  I illustrate the concept of de novo genetic disease by re-visiting Sophie, the girl with Dravet syndrome, and taking you through the recognition of the genetic basis of this severe epileptic encephalopathy and some of the exciting advances that are just around the corner in terms of potential genetic treatments for this condition.

Dr. Chao is an academic doctor practicing clinical genetics and genomics. She talks about her lifestyle and the promising future of clinical genetics.

I had an amazing three months in Sydney.  This episode outlines my time there - the people I met, the stimulation of the interactions and the challenges of reviewing data from many, many children with complex neuropathies.  We discuss two children - one a baby with a severe early onset form of epilepsy known as West syndrome.  We look at treatment then and now and see how much we've learned as neurologists in the last few years. I also discuss a young boy who I only met once who had an extremely rare genetic neuropathy called giant axonal neuropathy. I outline the underlying genetic cause of this in brief. Finally I leave Sydney and return to the UK to start the next chapter in my career.  Before embarking on that in Series 2 we will meet another friend of mine who is now a senior academic in Clinical Genetics and he will have more stories to tell.

Genetic testing is on the cusp of a major revolution, which has the potential to shift not just how we understand our risk for disease, but how we practice healthcare. In the clinic today, genetic testing is used only in cases where we know that mutations have big impact on physiology (BRCA mutations in breast cancer, for example). But our knowledge of how our genetics influences our risk for disease has evolved, and we now know that many (tens of thousands to even millions) small changes in our genes, each of which individually has a tiny effect, combine to influence our risk profile. This new appreciation — coupled with powerful statistical methods and massive datasets — has fueled the creation of a new tool to quantify the risk of a broad range of common diseases: the polygenic risk score. On this episode, host Lauren Richardson (@lr_bio) is joined by Dr. Peter Donnelly, (@genemodeller Professor of Statistical Science at the University of Oxford and the CEO of Genomics PLC,) and Vineeta Agarwala, (@vintweeta physician-scientist and general partner at a16z), to discuss these scores and how they can reshape healthcare, away from a paradigm of treating illness and towards prevention and maintenance of health.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Lee P. Shulman, MD, FACMG, FACOG Cervical cancer is the fourth most common cancer in women worldwide, which makes it essential for us to keep ahead of advances in cervical cancer prevention—advances like a biomarker-based cytology test. Here to discuss this and other recent advancements in cervical cancer screening is Dr. Lee Shulman, the Anna Ross Lapham Professor in Obstetrics and Gynecology in the Division of Clinical Genetics at the Feinberg School of Medicine at Northwestern University.

The story of a young mother who unwittingly left behind a vast medical legacy. Henrietta Lacks died of cancer in Baltimore in 1951 and though she never gave consent to her tissue being used for research, doctors at the time found that her unusually virulent tumour had extraordinary properties. As her cells multiplied in labs around the world, they helped make possible all sorts of medical breakthroughs, from the polio vaccine to cancer drugs and IVF treatment. But it took the Lacks family decades to discover what was going on, and the story raises questions for all of us – about medical ethics, institutional racism, and our right to privacy. Joining Bridget Kendall to discuss this remarkable story are: Henrietta Lacks' grandson David Lacks Jnr who's on the board of the HeLa Genome Access Working Group; the award-winning science writer, Rebecca Skloot, whose book The Immortal Life of Henrietta Lacks brought the story to the world's attention a decade ago; and Sir John Burn, Professor of Clinical Genetics at Newcastle University. Produced by Jo Impey for BBC World Service Image: Henrietta Lacks Image credit: Lacks Family

Integrating AI in healthcare with special focus on genetics https://outcomesrocket.health/fdna/2019/09/

In this episode, Dr. Slavin sits down with Michael Hall, MD, Fox Chace Cancer Center, to discuss how he got to where he is today, his department of clinical genetics, and how he thinks COVID-19 will change the world of cancer genetics. About Our Guest: Dr. Michael Hall is Chair and Professor of the Department of Clinical Genetics at Fox Chase Cancer Center. He is a physician-scientist, medical oncologist, and an expert in gastrointestinal cancers, particularly those cause by hereditary syndromes.

Dr. Brad Tinkle, one of the leading specialists in the treatment and diagnosis of hypermobility disorders, answers many of the key questions relating to hypermbility disorders: how rare (or common) is it? How do we treat it effectively? How do we increase awareness? How do we use social media responsibly? And so much more. It's a can't miss conversation that we hope you enjoy! Dr. Tinkle is an MD, PhD clinical geneticist at Peyton Manning Children’s Hospital in Indianapolis, Indiana. Previously he has been the Medical Director of Clinical Genetics at Advocate Children’s Hospital in Chicagoland and was a clinical and clinical molecular geneticist as well as the associate director in the Clinical Molecular Genetics Laboratory at Cincinnati Children’s Hospital Medical Center (CCHMC). He specializes in caring for individuals with heritable connective tissue disorders such as Ehlers-Danlos syndromes, Marfan syndrome, osteogenesis imperfecta, and achondroplasia. He served as director of the Skeletal Dysplasia Center at Cincinnati Children’s Hospital, co-director of the Marfan/Ehlers-Danlos Syndrome Clinic, as well as director of the Connective Tissue Clinic. Dr Tinkle earned a bachelor’s in science for engineering (BSE) in genetic engineering from Purdue University and he received his Ph.D. in Human Genetics from George Washington University in the District of Columbia. Dr. Tinkle attended medical school at Indiana University. His pediatric/clinical genetics residency and clinical molecular genetics fellowship were completed at Cinncinati Children’s Hospital. Dr. Tinkle authored the “Joint Hypermobility Handbook: A Guide for the Issues & Management of Ehlers-Danlos Syndrome Hypermobility Type and the Hypermobility Syndrome” which Won an Award for Publication Excellence (APEX) in healthcare. Dr. Tinkle’s other published book is called Bendy Wendy and the (Almost) Invisible Genetic Syndrome: A story of one tween’s diagnosis of Ehlers-Danlos Syndrome / joint hypermobility. Both books can be found on Amazon. Dr Tinkle has also authored numerous peer reviewed medical journal articles and was a member of the International Consortium of Ehlers-Danlos Syndromes and related disorders. Previously, Dr. Tinkle served on the Board of Directors and on the Professional Advisory Network of the Ehlers-Danlos National Foundation.

Over the course of the past decade or so, there's been a huge influx of genomic data due to better and more affordable sequencing technologies. How does anyone make sense of it all?  Simon Sadedin joins the show to answer this question and explain his role as a bioinformatician at Victorian Clinical Genetics Services. He talks about the following: How useful bioinformatics is and why it's become increasingly necessary in recent years What types of difficulties and philosophical dilemmas are encountered by clinical geneticists How short-read sequencing differs from long-read sequencing in important ways Victorian Clinical Genetics Services perform genetic and genomic testing for patients who have or are at risk of developing rare genetic disorders. The amount of data that can be gathered in this field of work is significant, which can complicate the process of providing patients with easy-to-understand, useful information that applies to their lives and the lives of their loved ones. This is where bioinformatics aims to be most useful. Sadedin explains the three primary roles of the bioinformatic work he carries out at Victorian Clinical Genetics Services, and explains that the ultimate goal is to improve patients' experiences and the quality of healthcare on the whole. He also talks about the ways in which it can be a challenge or even impossible to elucidate what a certain genetic or genomic result means for a specific person, the advantages and drawbacks of current versus emerging sequencing technologies, and how useful it is to obtain genomic data from people who are unaffected by certain rare genetic disorders.   For more, visit https://www.vcgs.org.au/ and https://www.mcri.edu.au/.

Today's show features Melanie Corbman. She is the Manager, Clinical Genetics at Cancer Treatment Centers of America.  Melanie shares a fascinating story of how she came to the field of Genetics and genetic counseling and the great work that CTCA is doing with patients around that.  Our second guest is Heather Annechiarico. She is the owner of Wine Dive, the first wine-focused bar and exclusive bottle shop with a seriously casual bent. The concept is simple, nothin too fancy but everything fabulous.

Dr. Brad Tinkle, one of the leading specialists in the treatment and diagnosis of hypermobility disorders, answers many of the key questions relating to hypermbility disorders: how rare (or common) is it? How do we treat it effectively? How do we increase awareness? How do we use social media responsibly? And so much more. It's a can't miss conversation that we hope you enjoy! Dr. Tinkle is an MD, PhD clinical geneticist at Peyton Manning Children’s Hospital in Indianapolis, Indiana. Previously he has been the Medical Director of Clinical Genetics at Advocate Children’s Hospital in Chicagoland and was a clinical and clinical molecular geneticist as well as the associate director in the Clinical Molecular Genetics Laboratory at Cincinnati Children’s Hospital Medical Center (CCHMC). He specializes in caring for individuals with heritable connective tissue disorders such as Ehlers-Danlos syndromes, Marfan syndrome, osteogenesis imperfecta, and achondroplasia. He served as director of the Skeletal Dysplasia Center at Cincinnati Children’s Hospital, co-director of the Marfan/Ehlers-Danlos Syndrome Clinic, as well as director of the Connective Tissue Clinic. Dr Tinkle earned a bachelor’s in science for engineering (BSE) in genetic engineering from Purdue University and he received his Ph.D. in Human Genetics from George Washington University in the District of Columbia. Dr. Tinkle attended medical school at Indiana University. His pediatric/clinical genetics residency and clinical molecular genetics fellowship were completed at Cinncinati Children’s Hospital. Dr. Tinkle authored the “Joint Hypermobility Handbook: A Guide for the Issues & Management of Ehlers-Danlos Syndrome Hypermobility Type and the Hypermobility Syndrome” which Won an Award for Publication Excellence (APEX) in healthcare. Dr. Tinkle’s other published book is called Bendy Wendy and the (Almost) Invisible Genetic Syndrome: A story of one tween’s diagnosis of Ehlers-Danlos Syndrome / joint hypermobility. Both books can be found on Amazon. Dr Tinkle has also authored numerous peer reviewed medical journal articles and was a member of the International Consortium of Ehlers-Danlos Syndromes and related disorders. Previously, Dr. Tinkle served on the Board of Directors and on the Professional Advisory Network of the Ehlers-Danlos National Foundation.

By Michael Tetreault, Dr. Dana Simpson and Dr. Alex Mason Today we sit down on The DocPreneur Leadership Podcast with two very special Doctors to discuss the role clinical genetics plays in treating a patient today and what role this will play in the exam room and in a medical office in the near future. Dana (Kostiner) Simpson, MD received her B.A. in Biology at U.C. San Diego (UCSD) and her medical degree at George Washington University School of Medicine in D.C. She completed her Internal Medicine Residency at the University of Colorado Health Sciences Center (UCHSC) in Denver and did her Genetics Fellowship at U.C. San Francisco (UCSF). She worked as a Clinical Geneticist at Kaiser Permanente, Northwest from 2002-2019, and also worked in the Internal Medicine float pool for the first 7 years. She worked as Chief of the Genetics Department for the latter 12 years. She joined Specialist Telemed as a founding member of STeM-Gen in 2019. Dana lives with her husband and two young children in Portland, Oregon. In her free time, she enjoys earning Splat point at Orangetheory Fitness, building legos with her kids, going to Blazer games, and getting some culture at the Oregon Shakespearean Festival. Dr. Alex Mason is a practicing neurosurgeon with a passion for telemedicine. He has been involved in outreach telemedicine projects since his training was completed in 2008, starting with working at Grady Hospital in Atlanta, GA. Understanding and seeing the significant challenges of access to healthcare, he began working with organizations to establish meaningful measures of patient access to specialists throughout the country. As a medical advisor to Specialist Telemed, he has been instrumental in identifying both traditional specialties that are underserved, as well as new specialties such as TeleGenetics that are in high demand and have had challenges with regard to access. RESOURCES MENTIONED www.SpecialistTeleMed.com www.ConciergeMedicineToday.com www.CONCIERGEMEDICINEFORUM.com

Integrating AI in healthcare with special focus on genetics

Dr Amit Khera:                  Welcome to Circulation On The Run. Our weekly podcast summary and backstage pass to the Journal. I'm Dr Amit Khera, associate editor and digital strategies editor from UT Southwestern Medical Center in Dallas, and I had the distinct privilege of standing in for Dr Carolyn Lam and Greg Hundley this week. Twice a year, we are very fortunate to have some unique podcasts when we don't have circulation issues, and in the past we've met with many fellows in training and heard about some interesting studies that they're doing. Today we have a very special podcast we have not done before, and that is one where we had the opportunity to learn about our Circulation Family of Journals, and more importantly to hear from the dynamic editors in chief of these various journals. I think you're really going to enjoy it, we'll walk through and hear from each one of them, hear about some of the innovative things that are happening, some of the future that they see for their journal in their field, and I really enjoyed it, and I'm sure you will as well. So, without further ado, we'll start with our first editor. Dr Sunil Rao:                      I'm Sunil Rao. I'm an intervention cardiologist at Duke, and I'm the Editor-in-Chief for Circulation Cardiovascular Interventions, which is one of the daughter journals of the Circulation Family. We publish articles really related to the broad spectrum of interventional cardiology, from coronary interventions to peripheral arterial disease, and Endovascular interventions to structural heart disease interventions. We also published review articles in all of those areas, as well as any health policy or outcomes studies that are in that space. Dr Amit Khera:                  Tell us what are some of the innovative things that your journal is doing this year. Dr Sunil Rao:                      We're really excited about two things, one is our extremely successful Assistant Editor program that we launched last year at A.H.A. 2018. This is a program where we have five early career individuals that are within five years of completing their fellowship program who joined the editorial team at Circulation Cardiovascular interventions, and in that role they really learn a lot about the mechanics of how scientific publishing works, they commit to doing manuscript reviews, and receive feedback on improving their peer review process, and even independently handles some manuscripts as well, that are in their areas of interest. This is our way, I think, of encouraging the next generation to stay engaged with science, and with the scientific publishing process. It's been extremely successful. Assistant editors are part of our team for a two year term. So, in 2020, we will be selecting the next class of assistant editors, and after their term is ended, they join our editorial board as editorial board members. So, we're really excited about that, it's been an overall positive experience, for I think everybody involved. The second thing that we're really excited about is that we launched a social media presence for the journal, which it previously did not have. So, we have a very active Circulation Cardiovascular Interventions Twitter handle, I encourage all the listeners to join Twitter if you're not on Twitter, and if you are on Twitter please follow at Cirque intervened. It's " at C.I.R.C.I.N.T.V.". That is the official Twitter handle for our journal. Dave Fishman is our social media editor, and Chadi Alraies is our assistant social media editor, and we're not just tweeting out the articles, and providing summaries when the papers get published, we're holding Twitter journal clubs once a month ,and these have been extremely successful, it's an hour long Twitter journal club where the discussion gets very intense, and there's a lot of back and forth. We try to have the authors on as well, so that they can explain the rationale for their study, some of the challenges that they face when they are doing the study, and hopefully provide some implications for clinical practice, and what the next steps are. That's a way for us to engage our readership, it's almost a form of post publication peer review, which I think is becoming very popular. In addition, remember we don't have a print format of our journals, so this is a way to get the readership more engaged with the Web site, and to come to our website and learn what elsewhere publishing, and how they can get involve with the Journal as well, both as authors who submit their work, or if they want a peer review for us, please contact us and let us know. Dr Amit Khera:                  I really love hearing about the Twitter journal club, I know that they are well received, and certainly getting a lot of traction. Tell us about what initiatives or topics you're most excited about this year, and maybe some things that are coming later in the year. Dr Sunil Rao:                      We're really excited about the big areas in interventional cardiology, which are coronary physiology, we've published quite a few papers on looking at different physiological parameters, and how they can drive the appropriate use of PCI and how that affects outcomes. I think that's going to continue to be a huge topic over the next year, Certainly such a heart disease has exploded, and with the data on low risk patients undergoing TAVR, and having really good outcomes, we're seeing a lot more submissions in the low risk TAVR space, the other area that's really exploding right now is Mitral and Tricuspid Valve Interventions, one of the areas that I think has seen a tremendous amount of device innovation. So, we're seeing a lot of submissions from really high quality papers in that space, but I think it's also important to note, that unlike previous iterations of the Journal, we're actually having a review article, we're trying to have a review article every month on a major area that is burgeoning, so that the readership can understand the overall lay of the land, with respect to evidence, how that guy's clinical practice, and what's coming next. So, we've published quite a few review articles already, and there are more to come, and I think that's a really important way for the readership to keep current with what's going on in Interventional Cardiology. Dr Amit Khera:                  What about the advancing aspects of your subspecialty? There's so much going on in interventional cardiology, it's a bit dizzying, just tell us a little bit about some of the ways that your journal's helping advance that mission, not just now but perhaps in the future. Dr Sunil Rao:                      I think one of the challenges that we have at Interventional Cardiology, and maybe this is true across Cardiology, is that the evidence is developed very rapidly, and oftentimes it almost seems like the field is lurching back and forth in certain areas, a prime example of that is the drug coated balloon controversy for Peripheral Interventions. The Journal Of The American Heart Association published a meta-analysis, showing that there may be an association between the use of these devices and increased mortality, that has led to a lot of discussion in the interventional community, and quite frankly I think there's a fair amount of confusion out there about whether we should be using these devices, should we put a moratorium on these devices, is the signal real, if it is, what's the mechanism of death. So, a lot of conversation around that, in fact, it's led to what's going to be a focused FDA meeting in June, specifically on the drug coated balloon controversy. Where I see our journal playing a role is really in trying to, not only publish the latest science, which is rigorous in the field for controversial topics such as this, but also to help provide some context for that science, and I think our integrated strategy of original science review articles, and social media really helps us to communicate with the readership, and with the Interventional Cardiology community writ large, meaning not just physicians, but also Cath lab staff, nurses, noninvasive cardiologists who obviously have patients who are undergoing interventions, and even policymakers, to keep them abreast of what's going on, so that they can have the same level or base of knowledge, so that the conversation is on a level playing field. Dr Amit Khera:                  Okay, well you heard it from Dr Sunil Rao. Thank you for your time. Dr Kiran Musunuru:        I'm Kiran Musunuru, I'm the outgoing Editor-in-Chief of Circulation Genomic and Precision Medicine. Let me start by saying a little bit about the content of the journal, it considers all types of articles related to, as the name implies, Genomic and Precision Medicine, and more specifically, Clinical Genetics, the molecular basis of complex cardiovascular disorders, considered at a variety of levels, that can include a lot of different, what we would call Omics Techniques, from Genomics to Transcriptomics, Proteomics, Metabolomics, Metagenomics, and, so forth. It also deals with big data applications, that includes Electronic Health Record Data, Patient generated data combined with any of the things I've already mentioned, Genome Wide Association Studies, Pharmacogenomics, Gene Therapy, Therapeutic Gene Editing, Systems Biology. So, it's a pretty comprehensive look at all the various topics that would fall under the rubric of Genomic and Precision Medicine. Dr Amit Khera:                  Now, Dr Musunuru, you mentioned the outgoing Editor-in-Chief, let's introduce the incoming Editor-in-Chief, Thatcher Christopherson Semsarian. Dr Chris Semsarian:         I'm the incoming Editor-in-Chief. My name is Chris Semsarian, I'm a cardiologist at the Royal Prince Alfred Hospital in Sydney, Australia. Dr Amit Khera:                  What are some of the innovations you and the Journal are doing this year, or, what are some of the things you see coming in the future? Dr Kiran Musunuru:        Something I'm very excited about, is that we are just starting a pilot project with the American Heart Association's Institute for Precision Cardiovascular Medicine. The institute has a very nice platform called the Precision Medicine platform, and, in brainstorming last year, we realized there was a very nice opportunity to try to create a new type of journal article. There's also a big move in science nowadays to improve transparency, and rigor, and reproducibility, especially in science. The idea being that ideally other investigators should be able to take one team's work, and be able to run through the entire analytical process, and reproduce the original findings, and perhaps even find ways to improve upon those original findings, and, so we realized working with the institute's Precision Medicine Platform, we had the opportunity to actually make a new type of article, we think of, as the paper of tomorrow, a virtual article. The idea would be, that we would have primary data on the Precision Medicine Platform, the analytical tools used to process the data would also be on the Precision Medicine Platform, the analytical plan, in the form of a so-called Jupiter notebook, that basically takes people step by step through exactly which tools were used in which order, in which way, with which parameters, would be on the Precision Medicine Platform, and then there would be some verbal explanation, some background, to explain the context of these analysis, and to really put it into perspective, as how it fits into the body of literature, and so the idea would be, this would live on the Precision Map Platform in a virtual format, and then anyone else who is interested in this work could come, and actually directly interact with the data, and the tools, and the analytical plan, and could actually rerun the entire papers work from scratch, thus reproducing it, and then could actually tweak the analytical plan, or install tools of their own, and be able to build upon the work that had already been done. It's a very different way of thinking about journal articles, more as living entities rather than static work that just lives on a page, and is there as reported, and then never has an opportunity to be fully produced or improved upon. Dr Amit Khera:                  There's so much happening in the space of genomics, and obviously, we hear the word "Precision Medicine" so commonly. Tell us a bit about how your journal in specific is advancing the mission of your area. Dr Kiran Musunuru:        I'll say a little bit, and then maybe turn it over to Chris, give his perspective as the incoming Editor-in-Chief. I think it's a vibrant field, but it's also a very new field, it's evolving rapidly, and I think the Journal has a very important role to play, and not only reporting the results that are coming out of studies in this field, but actually having a role to play in helping to shape the field, helping to define the field, it's very exciting, it's very much in rapid evolution. Just ten years ago or so, when the Journal first started, we were just starting to see the first Genome Wide Association studies, and now we've gone so far beyond that.                                                 Now, again, we're talking about these large bio banks, we're talking about Precision Medicine, we're talking about applying this information in health care, we're talking about combining all of these various streams of data and many levels to be able to do studies, that are, I would even say, exponentially advanced beyond what we able to do just ten years ago, and so, it's very exciting times for the journal, then maybe I can ask Chris to share his thoughts on that. Dr Chris Semsarian:         Yeah Kiran, I mean, it's a great honor system to follow in your amazing footsteps, and what you've done for the Journal, and as the incoming Editor-in-Chief, I really want to sort of try, and build on the platform that you've established over the last few years, and really, one of the areas that I'm particularly interested in is the area of Translation of Genomic Findings. I mean, ultimately what we do in our lives, as clinicians, is to help patients improve diagnosis, to improve the treatment of these patients, and to be able to do studies with very basic understanding of how our genomes work, and how Narcotic Genes interact, and translating those findings into these improved diagnostic approaches, and even in guiding management is really exciting, I think, in terms of clinical medicine, and improving patient care as we look ahead. I really want to be able to continue to publish really, state of the art, novel, innovative, research areas, that you've already covered, Kiran, which would lead to better care of our patients, who are ultimately the beneficiaries of this type of amazing work.                                                 So, I'm really excited looking at the Journal, it's a tremendous area of interest and research, where there's twenty-two thousand genes approximately now genomes, and we really don't understand most of them in terms of their intricate function, and I figured it's a great time ahead, in terms of Precision Medicine. Dr Amit Khera:                  Okay, well, that was Dr Kiran Musunuru, and Christopher Semsarian, we appreciate both of your time today for Circulation on the Run. Dr Paul Wang:                   I'm Dr Paul Wang, I'm the Editor-in-Chief of Circulation Arrhythmia and Electrophysiology. Our Journal covers really the expanse of our field, going from basic mechanisms of arrhythmias, so very basic science work, to really clinical practice, clinical outcomes, to population based studies, and genetic based considerations in our field. So, we really feel we encompass the entire range, and there really isn't any topic within our area, that we don't feel is outside our realm. Dr Amit Khera:                  I know there's so many innovative things you're doing, Dr Wang, with your journal. Why don't you tell us a little bit about your plans for this year. Dr Paul Wang:                   We've been excited; our team has been at the Journal for two years now, and we focused on a number of different areas. So, I think one of our biggest advances, and we've tried to be more responsive to the authors, so we've really reduced the time to first decision very substantially, from over twenty days, to ten days or less, I think we hit a record of 7.8 days in the journal. So, really, we hope we're more responsive, we've involved the editorial board, we've substantially expanded it, so that more of our reviews of greater proportion going to our editorial board, which is a really fabulous, internationally recognized group, with really high quality reviews, so we've been very pleased, with both a level of science that we've received, as well as the level of the reviews that we have. One other area is, we really want to make sure that the reviewers, who do much of the heavy lifting, in addition to our editors for The Journal, and so we've established a new Reviewer Recognition Award System, they can be designated as silver, gold or platinum, and we've reached out to department chairs, or their deans, and recognizing that they won this prestigious award for their performance, and great work with the Journal, so there are a number of different things that, in fact, we think we've made some advances in, the other areas are really that of extending our reach, and so, one of the things we concentrated on, initially with the adding of podcasts, so we do that monthly.                                                 All the articles are now available in review, and then what we're starting at our new initiatives is, we'll be starting a Twitter Journal Club. I've been recording at least two of our articles, as the interview with the authors, and then we're going to be having a journal club, in which we will have the opportunity for people around the world to comment, and have a discussion that will really be exciting, we think. So, there are a number of other areas that we're thinking about, in terms of that kind of work. Dr Amit Khera:                  The field of Electrophysiology seems to be changing by the day, maybe you can tell us a little bit, about how the journal is advancing the mission of the field of electrophysiology. Dr Paul Wang:                   So, one of the things that we focused on is the role the Journal can play, in terms of connecting with other elements of our field, and one of the ways that we've really concentrated on is, in particular, working closely with the American Heart Association, and its committees. We're related to a number of committees, but particularly, there is a committee on Electrocardiography, Electrophysiology, part of the Clinical Cardiology Council, and so, we work very closely with that group, and, in fact, we've invited that group to create proposals for a number of review articles, state-of-the-art reviews, that we hope will come out in the next year or so. The ways in which we can tie together our committees to AHA overall, I think, is really the direction we're looking for our journal, and we feel we can play a very novel, and innovative role in that regard. We, for example, also reached out to the American Heart Association funded researchers in our area, and invited them to participate in the journal, participate in our committees, become fellows or FAHA's of the American Heart Association, so we really want to create this family, a real community, and sense of community, that we hope will stem from the Journal. So, we're very excited about the future, and what we might be able to achieve together. Dr Amit Khera:                  Thank you so much, Dr Paul Wang for your time today, and we appreciate your insights on Circulation, Arrhythmia and Electrophysiology. Dr Nancy Sweitzer:          Hi, I'm Nancy Sweitzer. I'm the Editor-in-Chief of the Journal Circulation Heart Failure. At Circ Heart Failure, we deal with all things related to heart failure. Heart failure is an expanding specialty, relatively new subspecialty in cardiology, and we're very interested in the physiology, and mechanisms of heart failure, as well as treatments of heart failure, and the innovative evolution of the specialty which includes Advanced Hemodynamics, Mechanical Circulatory Support, and transplant as therapies, as well as all Implanted Device Therapies, and new, and Innovative Pharmacologic, and Gene Therapies as well. Dr Amit Khera:                  Tell us a bit about initiatives, or features in Circulation Heart Failure, that you're planning on tackling not only this year, but into the future. Dr Nancy Sweitzer:          The effort we're most excited about at Circulation Heart Failure has been ongoing now for a little over a year, but continues, and is really focused on the emerging scientists in the Heart Failure Space; we call it our "Featured Emerging Investigator Spotlight", and this spotlight focuses on authors of manuscripts, who are within ten years of their terminal training, and can take full responsibility for the content of a manuscript. When we publish a featured emerging investigator article, which we've done more than half of the months since launching the feature in late 2017, we schedule a Twitter Journal Club with that author, where we participate, over the course of several hours, in pretty intensive conversation, about not only the science, but career development in Heart Failure Space, the importance of mentoring, and sponsorship obstacles that people are facing in development as physician scientists or scientists, and insights they may have into fostering success in the Heart Failure Space. This has been a great feature, we launched it because we feel that the emerging scientists, in the Heart Failure Space, need a virtual community in those critical years, before you have a lot of resources to start traveling, and setting up a network that's based on personal interaction, and we felt that, the modern era of social media was perfect for this. We found our emerging investigators are getting to know one another, they participate in one another's Journal Clubs, the Journal Clubs are incredibly fun, and interactive and we're getting a lot of Twitter engagement from the Heart Failure Community, there's a lot of "Twitteratti" in Heart Failure that really are engaged, and engaged with the Journal, which has really been fun for all of us, I think, so that's the thing we're most excited about. Dr Amit Khera:                  It's really wonderful to hear how you're spotlighting authors in creative ways. Tell us a bit about how your journal is advancing the mission of Heart Failure and Transplantation. Dr Nancy Sweitzer:          I see the journal as central to advancement of the subspecialty, as I mentioned earlier, Heart Failure is a relatively young subspecialty in the United States, we received a CGMC designation as a subspecialty just in 2008, just eleven years ago, and it's been a board certifiable subspecialty only since 2014. So, we're very young, and I think really developing into our own. We've seen tremendous growth in the number of people seeking subspecialty training in Advanced Heart Failure and Transplant Cardiology, and we are really enjoying helping the Journal evolve with the specialty, as it evolves, and that's happening very actively right now. So, I think what Heart Failure is in 2019 is different than what it was just five years ago in 2014. We're doing a lot more ,as I mentioned, Complex Chemo Dynamic Thinking, thinking about the path of physiology in our patients, and how we can target that effectively, not only with existing therapies, but with strategies, and, as I mentioned, the burgeoning growth of Mechanical Circulatory Support, and support devices, which the field has embraced quite actively, and The Journal is increasingly publishing content in these spaces, as well as the spaces of Advanced Heart Failure, but, I guess also, we're interested in every aspect of Heart Failure, from Complex Multidisciplinary Care Management, to Palliative Care, to the interaction of the heart with other organ systems, and Heart Failure such as the brain, we have a paper on Cognitive Function Abnormalities, and Heart Failure in this month's issue. So, the interaction with the brain, the kidney, the liver, many other organs, that are affected when the heart becomes quite ill with Advanced Heart Disease. So, basically we're interested in everything that touches Heart Failure Development Care, and treatment of patients with Heart Failure, and particularly we're interested in the newest and latest. We love publishing, and some of our highest impact papers in the last couple years have been new therapies, just being tested for the first time in patients with heart failure. Small studies that may not have large impact in terms of heart outcomes, but where we're learning about the pathophysiology of the disease, and new treatments, that's really exciting to us. We've published a couple of methods papers in the last year, really innovative models. One describing a model of pacing in mice, which has been a really challenging thing to do in Heart Failure, but several groups have now developed Tachycardia induced Cardiomyopathy models in mice, which is important for rapid discovery work, because mice have such a short reproductive span, and can be genetically altered, and then a recent publication on the methods paper, looking at a new initiative by the FDA, to potentially approve therapies based on patient reported outcomes, rather than just heart mortality and morbidity outcomes, so we're really excited about the innovations, and the Heart Failure Space, the work that describes where we're going as a field and as a profession. You'll see some features coming up in the journal, from opinion leaders across the globe on where this specialty sits in 2019, and where we, as the leaders in the field, can guide it as we move into our next decade, and I think that some of the most exciting work the journals doing. Dr Amit Khera:                  Thank you, Dr Sweitzer. We really appreciate your time today for the podcast, and your insights on the Journal. Dr Robert Gropler:          Good afternoon, I'm Rob Gropler. I'm the Editor-in-Chief of Circulation Cardiovascular Imaging. It's one of the journals within the family of Circulation Journals, and our focus is really on being the most influential source of leading edge imaging sciences, as it relates to transforming cardiovascular care, so what that means is, that we're interested in all imaging studies that are applied to the care of the cardiovascular patient, and although our primary focus is really on clinicians, and researchers, but we also want to expand our viewership, if you will, to anyone who is interested in how imaging is used to understand Cardiovascular Medicine, and to treat patients with Cardiovascular Disease. So, we are edged in all forms of imaging, this can be from MR, to echo, to nuclear, to CPT, to optical imaging, it involves all types of disease, ranging from Congenital Heart Disease, up to diseases in the elderly, it also involves not just it is in humans, but also understanding disease in the preclinical space, particularly as it helps us understand new technologies that may ultimately reach human use, either for investigational purposes, or ultimately, to be used in the treatment of a patient with Cardiovascular Disease. Dr Amit Khera:                  What are some innovative things you and the Journal are planning for this year? Dr Robert Gropler:          We're doing quite a few things. One of the first things we did, as you know, were relatively new, where we've only been an editorial team, if you will, for one year. One of the major efforts has been to increase our presence, in terms of digital media strategies, across the board. And so, this meant expand our Twitter presence, if you will. It also meant increasing our offerings in that digital space by, for example, having a journal club, what we would do is on a every other month basis, discuss a paper we published that's of significant interest via Twitter. And it would involve the authors, the associate editors who actually manage that study, as well as the editorialist who wrote about that study, and it leads to very unique insights into how that paper is being viewed by the scientific community at large, and also potentially how that information will be implemented in terms of transforming clinical care.                                                 We've added what we call a teaching file. If you think about imagers, imagers learn by seeing images. And the more they can see images, put them in the context of clinical cases, the more they understand what an image means when they see it. So, what we do now is we accept a large number of what we call imaging cases. These are specific unique cases that have a history, and then a short write up about them.                                                 And those are gathered each month, but then they're downloaded into a file. And then, anyone with access to the Journal can then look at, use to learn from, to potentially use for talks to enhance their own education the education of others. And we have found that to be, again, another offering that our readers particularly like. Dr Amit Khera:                  And how do you see Circulation Cardiovascular Imaging advancing the mission of imaging, which seems to be ever-expanding, and ever-growing? Dr Robert Gropler:          We're really in the education business. And what that means is that we're educating at a multi-scale level. Just educating a practitioner on what technology can do, how it's helping cardiovascular medicine, yes, that's important. But what we're also doing, is we're educating the scientists as to here as some of the new findings that were coming out because of imaging. And then that, in turn, will help direct them or signal them as to where is the science leading them, and what should be their next steps?                                                 We're also educating the general public as to what can imaging do, and how does imaging change cardiovascular medicine for the better, and what they can expect from that. And we're also educating the regulatory bodies, if you will, that determine what imaging can be done in the clinical environment and so on, and the importance of these imaging techniques.                                                 So number one, I think we always have to maintain that focus, as to that's our goal. Now, that being said, I think the question becomes how do you convey that concept? And where we have to continually evolve.                                                 And I think they were very smart years ago to make it a digital-only journal, as opposed to combined print and digital. So, I think that was actually very savvy. But the digital net component now has to expand. And that means our offerings have to reflect not just that people learn in different ways, that is, we have to have not just, if you will, a didactic or print equivalent component of a paper. But it also should be audio-based, such as this podcast. But they also need to be varied as in terms of the types of offerings, and their brevity or length, if you will. Dr Amit Khera:                  Thank you, Dr Robert Gropler, the Editor-in-Chief of Circulation Imaging. We really appreciate your time today. Dr Robert Gropler:          Thank you very much. You have a great day. Dr Amit Khera:                  Well, I'm sure you enjoyed this as I did. We really got incredible insight from the Editors-in-Chief of our Circulation family of journals. We learned so much about the broad array of subspecialties that they cover, and all the exciting and innovative things they're doing to really advance the missions of their fields, and also for the authors and for science.                                                 Well, again, I'm Amit Khera, associate editor from UT Southwestern, Digital Strategies editor for Circulation. And next week, you'll have your usual hosts, Carolyn Lam and Greg Hundley. Dr Carolyn Lam:                This program is copyright American Heart Association 2019.  

October 2018 See acast.com/privacy for privacy and opt-out information.

I had the pleasure of catching up with Genetic Counsellor Yasmin in this latest podcast. Yasmin discussed many issues related to genetic counselling including pharmacogenomics and genetic conditions hypercholesterolemia and cardiac genetics. More info can be found at https://www.insightgenomica.com.au/podcasts/

It was a pleasure having Ron as my first guest on my podcast. We covered many topics including Ron's private genetic counselling practice in Sydney, Australia, what genetic counselling actually is, prenatal genetic counselling, expanded carrier testing and the professional body for clinical genetics in Australia; the Human Genetics Society of Australasia. More info can be found at https://www.insightgenomica.com.au/podcasts/

Pediatric Grand Rounds for Wednesday, March 7, 2018 Laurie Demmer, MD. Director of Clinical Genetics at Levine Children’s Hospital

Being able to restore sight once it has been lost is an age-old dream of human kind. It seemed impossible until the discovery of stem cells. What are stem cells, and why are they so important and what does stem cell science mean for eye disease? Come and learn about stem cells and understand the science behind them. All are welcome at our community events, aimed at a general audience. We appreciate your gold coin donation to help cover the cost of running our information forums. Topics to covered: Using stem cells to understand blinding eye diseases Dr Duncan Crombie, Research Fellow, Neuroregeneration, CERA Saving vision using stem cells and ‘Cut and Paste’ technology Lisa Kearns, Orthoptist, Clinical Genetics, CERA Understanding the role of your immune system: pitfalls and opportunities for cell therapy Dr Matthew Rutar, Research Fellow, Centre for Stem Cell Systems, University of Melbourne Hype, hope and reality in stem cell therapy Associate Professor Megan Munsie, Deputy Director, Centre for Stem Cell Systems, University of Melbourne; Head, Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia Q&A panel discussion. More information: https://www.cera.org.au/events/2017-stem-cells-info-forum/

The DNA sequencing revolution is providing ever more data about genomes from all kinds of species, from humans to bacteria. But how do we make sense of it all? Who gets their hands on it? And how do we use it to benefit patients? We meet the scientists developing new computer tools to analyse and democratise global genomics. Plus, how your partner's genes affect you - assuming you're a mouse - and a shrunken gene of the month. Like this podcast? Please help us by supporting the Naked Scientists

There’s a basic assumption in our field today that has been around for some time. We think of medicine as on a direct and even continuum with science. That discoveries in genomics, for example, will lead directly to breakthroughs in medicine. But the breakthroughs on the medical side have been much more rare to date than those coming from the study of biology and genomics.

For Episode 7, we interview physician-scientist and JAX-GM Assistant Professor Travis Hinson. Travis discusses what his joint appointment with UConn Health means for his research into the genomic basis of cardiovascular disorders. We also got to explore Travis’s northward journey from Louisiana and through Philadelphia and Boston before finally settling in Connecticut. You’ll also hear us discuss cool in vitro assays, vacationing in Italy and the Big Easy, Cajun food, fishing (and noodling!), and the majestic Yard Goat.

CHI chats with Rebekah S. Zimmerman, Ph.D., FACMG, Director, Clinical Genetics, Foundation for Embryonic Competence. Dr. Zimmerman discuss the latest technologies she and her non-profit lab are working with and developing, including how the non-profit lab is different from a typical PGD lab. Dr. Zimmerman is one of our speakers for the Advances in NGS and Other Technologies session at the Reproductive Genetic Diagnostics conference. For details, visit http://www.Healthtech.com/Reproductive-Genetic-Diagnostics

Dr. Wendy Chung is the Herbert Irving Associate Professor of Pediatrics and Medicine and Director of Clinical Genetics at Columbia University. She received her undergraduate training at Cornell University and went on to receive her PhD in Molecular Genetics from Rockefeller University and her M.D. from Cornell University. Afterward, Wendy completed her Internship and Residency in Pediatrics, a Fellowship in Clinical Genetics, and a Fellowship in Molecular Genetics at the Columbia Presbyterian Medical Center. Wendy is the recipient of an American Academy of Pediatrics Young Investigator Award, the Charles W. Bohmfalk Award for Distinguished Contributions to Teaching in the Clinical Years, the Medical Achievement Award from Bonei Olam, as well as the Presidential Award for Outstanding Teaching from Columbia University. Wendy is with us today to tell us all about her journey through life and science.

Thomas M. Morgan, MD, Division of Medical Genetics and Genomic Medicine and Assistant Professor of Pediatrics, Vanderbilt University presented “Will the 21st Century be the Era of Eugenics?” on Thursday, March 6th from noon-1pm in the HSC Instructional Building (B Building), Room 302. The learning objectives include: become familiar with the history of eugenics; learn how eugenics is currently being practiced on a limited scale; and understand how genomic and reproductive technologies have turned eugenics from a theoretical debate to an imperative policy question. Dr. Morgan is board certified in Family Practice, Clinical Genetics, and Medical Biochemical Genetics. He completed medical school at Boston University, his Family Medicine Residency at Dartmouth and a Genetics Residency at Yale. Dr. Morgan has held an investigator role on multiple funded research projects and is widely published.

Thomas M. Morgan, MD, Division of Medical Genetics and Genomic Medicine and Assistant Professor of Pediatrics at Vanderbilt University presented “Will the 21st Century be the Era of Eugenics?” The learning objectives include: become familiar with the history of eugenics; learn how eugenics is currently being practiced on a limited scale; and understand how genomic and reproductive technologies have turned eugenics from a theoretical debate to an imperative policy question. Dr. Morgan is board certified in Family Practice, Clinical Genetics, and Medical Biochemical Genetics. He completed medical school at Boston University, his Family Medicine Residency at Dartmouth and a Genetics Residency at Yale. Dr. Morgan has held an investigator role on multiple funded research projects and is widely published. This Gheens Lecture was presented on Thursday, March 6th from noon-1pm in the HSC Instructional Building (B Building), Room 302.

Professor John Burn, Professor of Clinical Genetics at the Institute of Human Genetics in Newcastle Upon Tyne and a clinical director of Northern Genetics and the Director of Cancer UK: 'Iron on the Brain'