Podcasts about Gladstone Institutes

Can education and technology create a more optimistic future for humanity? Rod Roddenberry, CEO of Roddenberry Entertainment and son of Star Trek creator Gene Roddenberry, shares his vision for moving humanity forward through innovative education, biomedical breakthroughs, and the enduring philosophy of infinite diversity from infinite combinations (IDIC).Rod discusses the Roddenberry Foundation's focus on long-term solutions to systemic challenges, highlighting their work with the Gladstone Institute on groundbreaking stem cell research. He explores how artificial intelligence could revolutionize personalized learning and help develop crucial emotional and social skills alongside traditional education.Drawing from Star Trek's legacy of positive leadership and inclusivity, Rod explains how the franchise continues to inspire problem-solving through cooperation rather than conflict. He emphasizes the importance of embracing change, seeking diverse perspectives, and maintaining optimism while acknowledging current challenges.Key topics covered:The evolution of Star Trek and its continued relevance for modern audiencesHow personalized AI education could transform learningThe Roddenberry Foundation's approach to long-term philanthropyLeadership lessons from Star Trek captains Picard, Pike, and JanewayThe importance of maintaining optimism while working toward meaningful changeLove the show? Subscribe, rate, review, and share! http://thefuturistsociety.net/

The Gladstone Institutes in San Francisco is an independent biomedical research institution that empowers world class scientists to find new pathways to cure disease.

In this episode of the Epigenetics Podcast, we talked with Vijay Ramani from the Gladstone Institute to talk about his work on Single-Molecule Adenine Methylated Oligonucleosome Sequencing Assay (SAMOSA). Our discussion starts with Vijay Ramani's impactful contributions to the field during his time in Jay Shendure's lab, where he worked on several innovative methods, including RNA proximity ligation. This project was conceived during his graduate studies, aiming to adapt techniques from DNA research to investigate RNA structures—a largely unexplored area at the time. We delved into the nuances of his experiences in graduate school, emphasizing how critical it was to have mentors who provided room for creativity and autonomy in experimental design. Dr. Ramani then shares insights about his foray into developing more refined methodologies, such as in-situ DNA Hi-C, a revolutionary protocol tailored for three-dimensional genomic mapping. He explained the rationale behind his projects, comparing the outcomes with contemporaneous advancements in methods like Micro-C. The discussion highlighted the importance of understanding enzyme bias in chromatin studies and the need for meticulous experimental design to ensure the validity of biological interpretations. We further explored exciting advancements in single-cell genomics, specifically Ramani's work on developing sci-Hi-C. This innovative technique leverages combinatorial indexing to allow high-resolution mapping of chromatin architecture at the single-cell level, a significant leap forward in understanding the complexities of gene regulation. As we progress, Ramani detailed his transition from graduate student to independent investigator starting his own lab. He elaborated on the challenges and excitements associated with establishing his research focus in chromatin structure and function using advanced sequencing technologies. Employing various strategies, including the innovative SAMOSA assay, his research seeks to elucidate the mechanisms by which chromatin structure influences transcriptional regulation. We also discussed the heterogeneity of chromatin and its implications for gene expression. Ramani provided a fascinating perspective on how variations in chromatin structure could affect gene activity, highlighting potential avenues for future research that aims to untangle the complex dynamics at play in both healthy and diseased states.   References Ramani, V., Cusanovich, D., Hause, R. et al. Mapping 3D genome architecture through in situ DNase Hi-C. Nat Protoc 11, 2104–2121 (2016). https://doi.org/10.1038/nprot.2016.126 Nour J Abdulhay, Colin P McNally, Laura J Hsieh, Sivakanthan Kasinathan, Aidan Keith, Laurel S Estes, Mehran Karimzadeh, Jason G Underwood, Hani Goodarzi, Geeta J Narlikar, Vijay Ramani (2020) Massively multiplex single-molecule oligonucleosome footprinting eLife 9:e59404. https://doi.org/10.7554/eLife.59404 Abdulhay, N.J., Hsieh, L.J., McNally, C.P. et al. Nucleosome density shapes kilobase-scale regulation by a mammalian chromatin remodeler. Nat Struct Mol Biol 30, 1571–1581 (2023). https://doi.org/10.1038/s41594-023-01093-6 Nanda, A.S., Wu, K., Irkliyenko, I. et al. Direct transposition of native DNA for sensitive multimodal single-molecule sequencing. Nat Genet 56, 1300–1309 (2024). https://doi.org/10.1038/s41588-024-01748-0   Related Episodes Epigenetic Mechanisms in Genome Regulation and Developmental Programming (James Hackett) Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff) Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: podcast@activemotif.com

In this episode, host Lynn Reinke, PhD, ANP-BC, FAAN, FPCN®, ATSF discusses approaches to philanthropy with Amy Jacobs, MSN, RN and Catherine Pyke, M.A. Ed., board members of the Hospice and Palliative Nurses Foundation. Related Resources: Learn more about the Hospice and Palliative Nurses Foundation (HPNF) Contribute to HPNF's 2024 Annual Appeal About the Speakers: Amy Jacobs, MSN, RN Amy Jacobs received her BSN from Lock Haven University of Pennsylvania and her MSN from the University of South Alabama. Amy is currently a Hospice Compliance RN for Compassus. Prior to her current position, she held leadership positions in hospice, palliative care, and quality with BJC Homecare in St. Louis. She was an integral part in the development and opening of Evelyn's House, a 16-bed hospice inpatient house, in St. Louis. She also assisted in the implementation of a system-wide palliative care program. She has volunteered with HPNA and HPNF for several years as an award reviewer, member of the planning committee for the annual assembly, and a member of the HPNA Professional Development Advisory Council. She is especially proud to have facilitated support for the Emerging Leaders Award with HPNF and the BJC Institute for Palliative and Supportive Care.   Catherine Pyke, M.A. Ed.  Catherine Pyke worked for thirty years in non-profits in the San Francisco Bay Area, primarily as a program officer for the Hearst Foundations and more recently as a Philanthropic Advisor for the Gladstone Institutes in Mission Bay. She is the founder of Centerpiece Philanthropy, a consultancy that provides philanthropic advising and coaching, grant writing, strategic planning and group facilitation. She is the author of Jane Lathrop Stanford, Mother of a University. In addition to serving on the HPNF board, she serves as the Communications Chair for the San Francisco Region of the Order of St John, an international volunteer organization whose mission is to support St John of Jerusalem Eye Hospital and social and health care needs in the U.S. She recently completed two terms on the board of the Episcopal Impact Fund in San Francisco. An alumna of Scripps College in Claremont California, with a Masters in Education from Stanford University, she came to appreciate the contributions of innovative philanthropists, while visiting colleges, universities, medical centers arts organizations and social service agencies throughout the West. A native of Salt Lake City, she currently lives in Santa Rosa, California.

Plus Artist Weds Hologram Google's Project Jarvis to Enable Autonomous AI Web Navigation Google's upcoming “Project Jarvis” could allow AI to autonomously complete digital tasks, such as email management and web-based research, by navigating online like a human user. Set for release with the next Gemini model update, Jarvis represents a broader AI trend where tools can go beyond static responses to actively manage and complete tasks independently. Artist to Wed AI Hologram in Unique Performance Art Piece Artist Alicia Framis plans to marry Ailex, an AI-powered hologram she designed and trained on past relationships, as part of her Hybrid Couple project. The ceremony, blending art and technology, explores human connections with digital entities and raises questions on the role of AI in relationships.  Study Reveals AI Struggles with Real-World Contexts MIT and Harvard researchers found generative AI models, like those used in GPT-4, falter in real-world applications. While the models perform well in predictive tasks, they struggle when faced with changes, such as minor detours in navigation. The study suggests limitations in AI's understanding of physical environments.  AI-Powered Drones Enter Military Service Anduril Industries has introduced two advanced AI-powered drones, Bolt and Bolt-M, aimed at transforming military operations. Powered by Anduril's Lattice AI platform, these drones enhance tactical efficiency with features like autonomous navigation and modular payloads for munitions delivery. Their user-friendly touchscreen interface allows operators to control reconnaissance and precision strikes with ease. AI and Stem Cells Offer Hope for Treating Heart Defects in Newborns Heart defects, affecting 40,000 U.S. babies annually, could soon be addressed in the womb through AI and stem cell innovations. A partnership between Australia's MCRI and San Francisco's Gladstone Institutes, the "Decoding Broken Hearts" initiative, aims to treat congenital heart disease early, potentially eliminating the need for transplants.  Microsoft to Launch AI-Enhanced Tour of St. Peter's Basilica Microsoft President Brad Smith will unveil an AI-enhanced experience of St. Peter's Basilica, created with the Fabric of St. Peter. This project, part of Microsoft's AI for Cultural Heritage, allows visitors to explore intricate basilica details digitally, building on similar initiatives for historical sites in Greece and France.

Superimposed on an impressive body of work on the blood-brain-barrier and immune system, Prof Akassoglou and her collaborators just published an elegant study in Nature that centered on the direct binding os the SARS-CoV-2 spike protein to fibrin with marked downstream pro-inflammatory effects. The findings and potential treatments have implications beyond Covid, Long Covid to other neurologic diseases.Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to audio and to relevant papers, graphicsEric Topol (00:07):Well, hello this is Eric Topol with Ground Truths, and with me today is Katerina Akassoglou. She is at the Gladstone Institute and she is a remarkable neuroimmunologist who has been doing extraordinary work for three decades to unravel the interactions between the brain, blood vessels and the role of inflammation. So Katerina, there's a lot to discuss, so welcome.Katerina Akassoglou (00:40):Thank you. Thank you so much. It's a great pleasure to join.By Way of BackgroundEric Topol (00:43):It's really interesting going back in your career. First of all, we're thankful that you immigrated here from Greece, and you have become one of the leading scientists in this discipline of important discipline of neuroimmunology, which is not just about Covid that we're going to talk about, but Alzheimer's and neurodegenerative diseases. This is a really big hot area and you're definitely one of the leaders. And what I was impressed is that all these years that you've been working on the integrity of the blood-brain barrier, the importance of fibrinogen and fibrin, and then comes along the Covid story. So maybe what we can do is start with that, which is you've made your mark in understanding this whole interaction between what can get into the brain, through the blood-brain barrier and incite inflammation. So this has been something that you've really taken to the extreme knowledge base. So maybe we can start with your work there before we get into the important seminal Nature paper that you recently published.Katerina Akassoglou (01:57):Yes, of course. So since very early on, I was still a graduate student when we made the first discovery and at the time was like mid-90s, so it was really ahead of its time. That dysregulation of cytokine expression in the brain of mice was sufficient to induce the whole cascade of events, triggering neurodegeneration, demyelination in pathological alterations, very reminiscent of multiple sclerosis pathology. And it was really hard to publish that study at the time because it was not yet accepted that this regulation of the immune system modeling the brain can be linked to neurodegeneration. So that was 1995 when we made that discovery, and I became really interested, what are the pathogenic triggers that actually polarized the immune cells in the brain? So with this, of course, this transgenic animal was expressing TNF, it was an artificially made animal that we made, but naturally what were the triggers that would polarize the innate immune cells? So I looked really early on in this mice and what I found was that the very first event was leaks of blood-brain barrier. It was opening of the blood-brain barrier in this mouse before inflammation, before demyelination, before neuronal loss. And this is really what shaped the question that, is it possible that these blood leaks that happened very early in the pathology, could this be the instigators of pathogenic inflammation in the brain?Eric Topol (03:34):Yeah. So in a way, you got at this question because of the chicken-and-egg and what happens first, and you got to the temporal saying, which happened first as you said, the leak before you could see evidence of inflammation and being able to study this of course in the experimental model, which you couldn't really do in people. And what I love about the description of your career, which has been quite extraordinary contributions is connecting the dots between the blood, the inflammatory response and the brain. Perhaps no one has done that like you have. And before we get into the recent paper, a lot of people are not aware that a year ago, a group in the UK known as PHOSP-COVID, they published a really important paper in Nature Medicine of over 1,800 people who were hospitalized with Covid and they found that fibrinogen was the best marker for cognitive deficits at 6 and 12 months (Figure below)(04:40):So that's just one of many papers, but it's a particularly well done study that already before you got into this work that recently published had emphasized fibrinogen. And by the way, again, having spent a lot of years in clots in the arteries, for me, we have to just get it down to fibrinogen plus thrombin gets you to fibrin. Okay, so fibrin is a major player here when fibrinogen is cleaved. So here we have the basis that you established, which is the fibrinogen leakage into the brain, activating inflammation, activating microglia, which like the macrophages of the brain and inciting the whole process. And before we close, I want to not just talk about Covid, but Alzheimer's too. But now let's get into the study that you did, [Fibrin drives thromboinflammation and neuropathology in COVID-19] which is striking, I mean really striking. And can you kind of take us through, because you not only demonstrated the importance of fibrin in inciting neuroinflammation in this model, but also how you could reverse it or prevent it. So this, and you looked at it in many different ways, this was a systematic approach. Maybe you can take us through how you were able to make such compelling evidence.The Multimodal EvidenceKaterina Akassoglou (06:09):Yes, thank you. First of all, thank you for bringing up the human relevance because this was also our inspiration for the work that we did in the Covid study. So as you mentioned in Covid patients, fibrinogen unbiased mass spec analysis was identified as the predictive biomarker for cognitive impairment in Long Covid patients. And this was in addition to also neuropathology data about the abundance of fibrin deposition in the brain. And these were studies that were done by NIH that have found deposition of fibrin in the brain and the reports for the abnormal and puzzling coagulation in Covid that is not setting other infections and also in many cases not always relating with the severity of symptoms. So even mild cases of Covid also had increased coagulation. I was really intrigued by this human, all this evidence in human data, and I thought that maybe the way that we're thinking about this, that it's systemic inflammation that drives the clotting.(07:24):Maybe there's another aspect to this. Maybe there is a direct effect of the virus with the coagulation cascade, and in this way maybe this can be an instigator of inflammation. So this was the original idea to be able to reconcile this data from the clinic about why do we have this prevalence of coagulopathy in Covid. And of course, the second question is, could this also be a driver of the disease? And of course, we're in a unique position because we have been studying this pathway now for over 20 years to have all the toolbox, the genetic toolbox, the pharmacologic toolbox to be able to actually really address these questions with genetic loss of function studies, with a blood innate immunity multiomics pipeline that we have set up in the lab. And of course, with preclinical pharmacology in our ABSL3 facility. So we had the infrastructure in place and the source in place to actually really dissect this question with both genetic tools as well as also technology platforms.Eric Topol (08:29):And you had in vivo imaging, you're the director of in vivo imaging for Gladstone and UCSF. So you do have the tools to do this.Katerina Akassoglou (08:38):Yes. The imaging that you mentioned is really important because this is, we employed that very early in our studies over now 15 years ago. And the reason was sometimes from snapshots of histopathology, you cannot really understand the sequence of events. So by being able to image these processes, both neuronal activity, microglia activation, infiltration of peripheral cells in the brain, this is how we could see the steps that what happens early on and to be able to answer these chicken-and-egg questions that you mentioned. So these were very, they're very important experiments, especially at the beginning because they were hypothesis driving and we were able to ask the right questions to drive our research program.Eric Topol (09:26):Now was the binding of the spike protein to one key site in fibrinogen, was that known before? [See outstanding Figure below from Trends in Immunology]Katerina Akassoglou (09:36):No, this was not known. So there was evidence that there are abnormal clots in Covid, but it was not known whether the spike protein would directly bind to protein to the coagulation cascade. So one of the key discoveries in our study was to use peptide array mapping and be able to identify not only the binding, but exactly the domains on fibrin that spike binds too. And what we found was two key domains, one the inflammatory domain and the other the plasmin binding site, which is important for fibrin degradation. So this suggested a potential dual deleterious role for this interaction, both by maybe affecting inflammation, but also delaying fibrinolysis, which is the degradation of this toxic protein from the brain. And indeed, we found that this interaction was responsible for all these two aspects, including decreased degradation, more inflammation, but also at the same time increased, increased coagulation. So it was a really pathogenic interaction.Eric Topol (10:47):Yeah, actually it's pretty striking. You have these two sites, the plasmin cleavage site of fibrinogen, which as you say, we knew there was a problem with clots. We knew that, but we didn't know exactly the spike protein how exactly it was implicated, particularly with fibrinogen. And then this other site, the CD11b-C18, now that's fancy for surface receptors of macrophages. And basically, this is critical because it's this microglia activation in the brain, and I know you saw it in the lungs as well through this other site that spike protein activated. So you had a twofer here of things that you discovered that the SARS-CoV-2 spike protein was capable of doing. This was a really big revelation. And then you also looked at mice that were genetically manipulated. So maybe you can, because before we get to your antibody monoclonal, the ways that you proved this were, I mean, one thing after another is really systematic. So maybe you can teach us about that.Thanks for reading Ground Truths! This post is public so feel free to share it.Establishing CausalityKaterina Akassoglou (12:08):Yeah, sure. So the first was about chemistry experiment. So this of course, we had to get to the next step to see is there any causality for this pathway. So we employed genetic loss of function studies and we had knockout mice, either fibrinogen knockout mice, this mice have all blood proteins except fibrinogen, and they have a delay in coagulation so they don't clot properly. But we also had a mutant mouse, which is a fibrinogen NK mouse. And this was a mutation only within this inflammatory domain that you mentioned, inflammatory domain that binds to C11b-C18. Other names for this is of course complement receptor 3, Mac-1 (αMβ2). It's the same, many names for this receptor, that as you mentioned, is expressed not only in microglial in the brain, but also peripheral immune cells including macrophages as well as also neutrophils which are CD11b expressing.(13:12):So we now have genetic models to be able to look at both complete depletion of fibrinogen, but also a very specific mutation and very selective mutation that only blocks the inflammatory properties without affecting the properties of fibrin in hemostasis. And these mice were made many years ago by a very close collaborator, Jay Degen at the University of Cincinnati. So what we found is that when we block either the inflammatory domain or we completely deplete fibrinogen, there was this profound protection after infection in internasal infection with the virus in lung inflammation. And this was both suppression of oxidative stress and this pathogenic inflammation in the lung, but also decreasing fibrosis, which has been associated with also Long Covid. And the surprise came from the transcriptomic data. So when we did transcriptomic analysis in this mice in the lungs, we found perhaps the expected decrease in the immune signatures in macrophages. This was in line with our previous work in, as you mentioned, Alzheimer's models, multiple sclerosis models. But what also was really surprising is there was that genes that are associated with activation of NK cells were upregulated. And of course this was the first time we had infected these mice, previously we had not done an infection before. So I think that maybe because of this region we had not seen before in our data this immunomodulatory role of fibrin that not only surprises the macrophage response, but also increases these NK cells that are important for viral clearance.Eric Topol (15:00):So again, the finding another important unique finding is the natural killer (NK) cells and effect there from the activation of this, as you said, the inflammation site or the CD11b-C18 that we've been talking about. So now another layer of this, a dimension of your Nature paper was that you tested an antibody that you already had developed so-called 5B8. A monoclonal that specifically binds to the domain of the one we're talking about this inflammation domain of fibrinogen. So can you tell us about what that showed?Katerina Akassoglou (15:45):Yes, so we tested this antibody in different models of Covid, which were both models with neuroinvasion and models without neuroinvasion. So we used both transgenic mice for hACE2, the human ACE2 infected with Delta, but we also use mouse adapted viruses like Beta that is just in the wild type mice with no transgenic being involved that these are without neuroinvasion. And we wanted to see if the antibody had any potential protective effects. And what we found is that the antibody protected from inflammation in the lung. So the data looked so similar with a genetic mutation of this pathway, protection from inflammation, decreased fibrosis, increased viral clearance, so decreased spike and viral proteins in the lungs. But we also found a protection in the brain. So the brains of this mice, including both the models we used with neuroinvasion and without, they both have had microglia activation in the brain. And we also found neuronal loss in the Delta infected mice and the antibody protected from both neuroinflammation but also improved neuronal survival in the mice. Showing that there can be this despite regardless of which model we used, there was this protective effect suggesting that by blocking fibrin, either the periphery or in the brain, this could be protected for these models.Eric Topol (17:28):Yeah, so I mean this is fascinating because until now, until this report of yours and your colleagues at Gladstone, there was knowledge that there would be neuroinflammation from Covid, both in patients from various biomarkers and imaging as well as in experimental model. But what this did was take it to the fibrin story, and I guess that's one of the questions you nailed that how important fibrin is, but that doesn't necessarily rule out other triggers of neuroinflammation, right?Katerina Akassoglou (18:04):Oh, absolutely not. So I think that this is one of the mechanisms that can be very important, especially in some patients. But we know that there are additional of course mechanisms of neuroinflammation including auto-antibody responses, as well as also endotheliopathy that are persistent endotheliopathy, this can be interacting also with each other. So I think that it's important for future research that we understand how do these mechanisms feed into each other? Are there a positive feedback loops between autoimmune mechanisms and coagulopathy and endothelial dysfunction with inflammation? But I think most importantly, I think that if we're thinking of this in the context of patients, can we identify patients with mechanism that might be more prevalent in specific cases of Long Covid and tailor our potential future clinical trials towards the needs of Long Covid patients?Towards TreatmentEric Topol (19:06):Absolutely. I did interview some months back on Grounds Truths, Michelle Monje at Stanford, who I'm sure and interact with, and she's also works not so much on the fibrin side, but on neuroinflammation and the likeness between this condition in people and chemo brain because of the inflammation that's seen there. So we've talked about the multiple triggers that could contribute to brain inflammation, which I think most people would say in Long Covid this is one of the most, besides obviously the lack of energy, the profound fatigue and disability, but the cognitive function hit, not just brain fog is often profound. And we've just seen some reports about that, and particularly in hospitalized patients, how bad that can be. So that gets us to a potential treatment. Now, one of the things that's out there dangling, there's many things that people have talked about in terms of why can't we have a treatment for Long Covid?(20:13):And now of course this fibrin pathway, if you will, lends itself to many possibilities, whether it's anticoagulants or fibrinolytics like a tPA or things like nattokinase, which is a Japanese food enzyme that you could get at the nutrition centers or whatever. What are your thoughts? Because we don't have any good studies. There are all these little, tiny studies and they don't provide much conclusion, and you have an antibody that could potentially be effective. As I understand it, you set up a company some years ago, Therini Bio and used to be called MedaRed. You're the first woman scientist at Gladstone to develop a spin out company, which is another point of congratulations on that. But could the antibody be tested in patients or what do you think about these other possibilities?Katerina Akassoglou (21:15):Yes, yes. These are great questions. So first of all, the different approaches that you mentioned have very different mechanism of action. So degrading fibrin, the degradation products of fibrin also can have deleterious effects. The dimer, for example, can be very pro-inflammatory. So at the same time, blocking coagulation can also have a diverse effects because this can lead to excessive hemorrhage. So the approach that we took was to selectively block the inflammatory properties of fibrin without affecting beneficial effects of the molecule in normal hemostasis. So the challenge when I made the antibody was to be able to dissect these two functions of fibrin. It's our most important clotting factor, but at the same time, a molecule with profound pro-inflammatory capacity. So the observation that these two domains, the clotting domain and inflammatory domain were not overlapping, was really the foundation of this invention was that we could maybe create this antibody to be able to target them in a selective way.Other Neurologic Conditions (22:31):So the antibody I developed is neutralizing blood toxicity by blocking the inflammatory domain of fibrin without adverse coagulation effects. And it's now completing phase one trials. So it has already completed the single ascending dose at 40 milligram per kilogram. It's interim data were announced already for this trial, with no safety signals. So if the antibody completes this year, the phase one trials, then it should be possible to be tested in different patient populations. You mentioned before chemo brain, and I think it's important that we think that blood-brain barrier disruption occurs among many neurological conditions, and it's an early event associated with early disease onset and worse prognosis in multiple sclerosis, Alzheimer's disease, traumatic injuries. So I think that it's by developing a strategy, therapeutic strategy to neutralize blood toxicity, this can have applications in a wide range of neurological conditions with vascular dysfunction.Eric Topol (23:54):Yeah, no. In your Nature Immunology 2020 piece [Figure below], you started with the 1883 identification of multiple sclerosis (MS) lesions were “engorged with blood”, the first link between blood leaks and brain inflammation. So this has enormous potential. And what I like about this Katerina is that you've dissected the clot component versus the inflammatory trigger of the fibrinogen and fibrin story. And this is so vital because if you keep throwing these things that just going to work on the clot and not deal with the pro-inflammatory consequences, then you're going to get the wrong impression that clots are not that important. And by the way, you did mention, and I want to come back to that too, endothelial inflammation, which is another feature of Long Covid is another kind of interactive part of this because when the lining of the blood vessel is inflamed, it will attract microthrombi and also be a participant in this whole affair. What do you think about Alzheimer's and the prospects of being able to interfere with Alzheimer's? We have 20 years in someone before this process takes hold and meets clinical manifestations. Would an antibody like this ever be useful along the way?Katerina Akassoglou (25:29):Yeah, so well, our antibody was tested first in Alzheimer's, this models when it was originally published, and we performed reversal trials in Alzheimer's models. So we dosed mice when they have established amyloid plaques, microglia activation, neuronal loss, and we could reverse this effect so it could increase cholinergic neurons in mice, reduce inflammation in a very selective way, only the neurotoxic part of inflammation and for genetic depletion of this pathway with akin mice in Alzheimer's disease. Also, improves from cognitive impairment, and we now have a new paper in Cell Press that is showing this effects also with really nice and unbiased machine learning models for behavioral segmentation [Figure below].So I think that there is the data both from genetic studies and the antibody show projection in Alzheimer's disease. And of course, as you might have read the recent Lancet report from the Lancet committee on dementia that identified the vascular risk factors as the key contributors, especially post sporadic cases of Alzheimer's disease that is over 90% of Alzheimer's disease that is not genetically linked.(26:58):So I think that there is a real need in Alzheimer's disease to be able to block this vascular induced pathology. And an antibody like the fibrin neutralizing therapy could be positioned to be protective from the vascular induced immune-mediated neurodegeneration in this disease as well. I mean, ultimately, I think that we need to be thinking the terms of efficacy. So we want to have a drug that is efficacious, but we also want it to be selective. And the selectivity is really important because the immune system has so many protective functions. So if we block phagocytosis, we end up with more debris, decrease of neurorepair, anti-myelination. So by blocking a ligand here and not blocking, not eliminating a cell type or blocking a global pathway in this cell, but biologic a single ligand, I think we have been able to achieve this balance between efficacy, but also safety because we only block this neurotoxic populations and not the entire innate immune response that also has been beneficial for metastatic functions in the brain.Blocking NeuroinflammationEric Topol (28:19):So you're bringing up another critical concept about targeting the inflammation, this kind of goldilocks story of how much you interfere with the immune response and how much you are able to reduce the adverse pro-inflammatory effects. So that gets me to what if we don't know in any given patient how much fibrin is having a role in their Long Covid. Although we know it has to be a prominent feature because we saw it in, not just a hospitalized patient series that I mentioned we reviewed, but other papers as well. But what about if you just try to take on inflammation like through a GLP-1 drug or cGAS–STING or any of these really strong anti-inflammatory pathways. Do you see a difference in a generalized approach versus a specific approach that is really fibrin centered?Katerina Akassoglou (29:22):Yeah, so we have a focus actually on both because we wanted to dissect the downstream intracellular pathways of fibrin, and it's interesting that we can find specific inflammatory mediators that potentially can also be targeted as well, to be able to preserve that specificity, which I think is really important because if we don't preserve the specificity, we'll end up with a lot of adverse effects by eliminating major immune responses. But the point that you raised I think is really important because it's not enough to have an efficacious and selective drug if you don't know the patient population that will benefit from this drug. So I think that in addition to the drug discovery studies, it's important to develop also biomarker programs with both fluid biomarkers, but also imaging biomarkers to be able to identify the patient populations that will benefit from such treatment.(30:25):So if for example, a patient population has a fibrin deposition, blocking only downstream might not be enough, and it might be really important to neutralize this fibrin toxicity in the brain of patients. And with our target engagement studies, we show that at least in animal models, the antibody can be there. So I'm very encouraged by also programs that are going on now in the scientific community to develop noninvasive ligands to be able to image fibrin in the brain that are already tested in different patient populations like multiple sclerosis. Because I think we're going to learn so much from the biology as we start interrogating and asking these questions now in different patient populations.Eric Topol (31:14):I think that's a vital point you're making because the success of a clinical trial here in a clinical syndrome that is mosaic with lots of different types of pathways. If you can nail down the patients that would have the most to stand to benefit from a particular intervention, that the chance of you not missing the benefit that is matching the marker, what image marker or other markers is so vital. Well, we've talked, I think, about some fascinating discoveries that you and your colleagues have made. I mean, it's really extraordinary, and obviously we need this in Long Covid. But you know what, Katerina, it's almost made me think that you were warming up to this for three decades, that somehow or other you were working on all this stuff and then came Covid. Is that how you see it, that somehow or other you didn't know that all the work you were doing was going to wind up in this space?Katerina Akassoglou (32:18):Oh, I never thought I would work in a virology project. This collaboration started over Zoom with Warner Greene. We were both sheltering in place. It was the beginning of the pandemic, and the first reports were coming out about this puzzling coagulopathy. And our labs were hardly operational at the time, as you know, we had to close down our labs for a while. And however, this was a very big problem, and we thought that this is our role as scientists. If we feel that we can contribute and we have the tools to contribute, we felt that it's important that we pivot some part of our research, and even we wouldn't be doing this before, but it was important to pivot a part of our research and collaborate. And I think studies like this, this study would have been impossible without a team of collaborators. As you know, there were over 50 scientists involved at Gladstone, UCSF, UCLA, UCSD, Stanford University. Without collaboration, this study wouldn't be possible. So I'm really grateful to everyone who came together to solve this problem because I think that's what scientists should be doing. We should be solving problems as they arise.Eric Topol (33:41):Well, and also, I think a lot of people don't realize that, for example, when the Covid vaccines came along, people think, oh, well, it all got done in 10 months since the sequence of the virus, when in fact it took 30 years at least between all the factors that went into having an mRNA and sequencing virus and nanoparticles. And in many ways, your arc of this work is like that because it took three decades to have all the tools and the basic understanding, the antibody that you had developed for different reasons and this fascinating unraveling of what's going on in the model and undoubtedly in some patients at least as well. So before we wrap up, have I missed anything about this just remarkable work you've done?Katerina Akassoglou (34:33):Oh, thank you. I just want to thank you for this discussion and thank you for emphasizing the different areas and the different decisions that this pathway can have implications both for our understanding, our basic understanding of the blood brain immune interface, as well as also potential translation. And I think that the curiosity sometimes of how things work, I never thought it would work on Covid, like you mentioned at the beginning, but I think that basic science and curiosity driven science can sometimes lead to discoveries with translational implications that hopefully might benefit patients one day.Eric Topol (35:21):Yeah, well, undoubtedly it will. We're indebted to you, Katerina and all the folks that you have teamed up with, connecting the dots at the neurovascular interface. Phenomenal work and will follow the subsequent with great interest and it will likely not just a story about Long Covid, but other areas as well, so thank you.*********************************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly help fund our summer internship programs.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

In this episode, taken from a live a16z event, Bio + Health general partner Vineeta Agarwala moderates a panel of UCSF faculty founders, including Michelle Arkin, Jimmie Ye, and Natalia Jura (full bios below). Together, they discuss fundraising, the decision to stay in or leave  academia after founding a company, and their tips for managing the IP process. Michelle Arkin is a professor of pharmaceutical chemistry at UCSF, chair of the Department of Pharmaceutical Chemistry, and a co-director of the Small Molecule Discovery Center at UCSF. Professor Arkin is also a cofounder of both Elgin Therapeutics and Ambagon Therapeutics.Jimmie Ye is an associate professor of medicine at the Institute for Human Genetics at UCSF and an affiliate investigator at Gladstone Institutes. He is also the cofounder of Dropprint Genomics and Survey Genomics.Natalia Jura is a professor in the Department of Cell and Molecular Pharmacology and an investigator at the Cardiovascular Research Institute at UCSF. Professor Jura is also an associate director of the Quantitative Biosciences Institute. She is a cofounder of Rezo Therapeutics.

EPISODE 1536: In this KEEN ON show, Andrew talks to the KresusLabs founder and CEO Trevor Traina about his super app in which, he claims, we will store all our Web3 data Technology entrepreneur and private investor Trevor Traina has founded and co-founded several successful enterprises, including the Internet's first comprehensive product-comparison guide, CompareNet. After Microsoft purchased CompareNet in 1999, he stayed on board for two years as the site evolved into MSN's shopping channel.Most recently, Trevor Traina founded and served as Chairman of DriverSide, a resource assisting consumers with all aspects of owning and maintaining vehicles. A major public corporation acquired the firm in 2011. Recognized for his expertise, Trevor Traina was appointed by the Mayor to the Technology Advisory Council of the City of San Francisco. He has also held responsibilities on business and charitable boards for Verdiem Corporation, Swanson Vineyards, the Fine Arts Museums of San Francisco, the Gladstone Institutes, and other organizations. Trevor Traina completed his undergraduate degree at Princeton University and graduate degrees at Oxford University and the Haas School of Business at the University of California, Berkeley. Named as one of the "100 most connected men" by GQ magazine, Andrew Keen is amongst the world's best known broadcasters and commentators. In addition to presenting KEEN ON, he is the host of the long-running How To Fix Democracy show. He is also the author of four prescient books about digital technology: CULT OF THE AMATEUR, DIGITAL VERTIGO, THE INTERNET IS NOT THE ANSWER and HOW TO FIX THE FUTURE. Andrew lives in San Francisco, is married to Cassandra Knight, Google's VP of Litigation & Discovery, and has two grown children. Learn more about your ad choices. Visit megaphone.fm/adchoices

Genomics may seem like a field of study with minimal impact on our daily lives. But not for much longer — and certainly not to Dr. Deepak Srivastava, a cardiologist and president of the Gladstone Institutes. Rapid technological advances in this field are starting to surface across health care with significant and promising benefits. “The new world,” says Dr. Srivastava, “is going to be one where, as we identify the known genetic causes, we no longer have to accept that that mutation exists. We finally in medicine have the opportunity to think about curing disease.”The nonprofit Gladstone Institutes focuses on four key disease areas – the heart, brain (including Alzheimer's and Parkinson's), viral (like HIV and Covid), as well as immunologic disorders. On this episode of Healthy Conversations, Dr. Srivastava tells about advances like reprogramming support cells in the pancreas into new insulin-producing cells for diabetes: “So we can take skin or blood cells from any adult and turn those into cells that behave just like a human embryonic stem cell, which has the property that it can become once again any of our over 200 different cell types in the body.” The future may indeed be here, sooner than you think.    Learn more https://gladstone.org/

This week, Elphege Nora shares personal thoughts on his journey from Paris to CaliforniaElphege discovered at an early age that the best way to explain who we are is to look back at where we come from and our evolutionary trajectoriesFrom his earliest research experiences, Elphege was intrigued about the sociology of the lab and it's unusual social etiquetteHe shares his memories of working with Edith Heard and what she taught him about mentoringHe claims that personality tests can be useful for understanding how to interact with colleagues and team membersElphege recommends that it is good to present your work early at conferences in order to gain visibility and attract recruitsHe shares thoughts about the different scientific approaches he has encountered in Europe and the United StatesElphege shares how his interaction with his (famous) father pushed his to think about the abstract and conceptual impacts of his workHe had to learn when it's important to strive for perfection and when it is notHe stresses the importance of trust in mentoring relationshipsHe concludes ‘You need to understand what you're good at and what you suck at'He mentioned these institutions, researchers and resourcesCurie Institute : https://institut-curie.org/Gladstone Institute : https://gladstone.org/Edith Heard : https://thelonelypipette.buzzsprout.com/1356877/11387623-tlp-12-science-without-frontiers-edith-heardMax Greenberg : https://thelonelypipette.buzzsprout.com/1356877/5520439-tlp-1-navigating-the-path-to-team-leader-maxim-greenbergBenoit Bruneau : https://twitter.com/benoitbruneauMoshe Yaniv : https://en.wikipedia.org/wiki/Mosh%C3%A9_YanivFrancois Jacob : https://en.wikipedia.org/wiki/Fran%C3%A7ois_JacobPierre Nora (Elphege's father) : https://fr.wikipedia.org/wiki/Pierre_NoraTo find out more about Elphege visit his websites or follow him on TwitterLab website : https://noralab.ucsf.edu/index.php/the-team/Twitter : https://twitter.com/elphegenoralab?lang=enYou want to support our work ? Buy us a coffee ! ==> https://www.buymeacoffee.com/lonelypipetteTo find out more about Renaud and Jonathan : Twitter : https://twitter.com/LePourpre LinkedIn : https://www.linkedin.com/in/renaudpourpre/ Twitter : https://twitter.com/Epigenetique LinkedIn : https://www.linkedin.com/in/jonathanweitzman/%20 More about the soundtrack :Music by Amaria - Lovely Swindler https://soundcloud.com/amariamusique/

Welcome to Part 2 of a special two-part RealTalk MS series highlighting conversations with past recipients of the Barancik Prize for Innovation in MS Research.  The Barancik Prize is awarded at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, a meeting better known as the ACTRIMS Forum. Several past Barancik Prize winners gathered at the 2023 ACTRIMS Forum to celebrate the 10th anniversary of the Barancik Prize, and I took that opportunity to chat with this remarkable group of MS research all-stars.  Part 2 of Barancik Prize Conversations features the 2018, 2020, and 2022 Barancik Prize winners. Dr. Katerina Akassolgou, of the Gladstone Institute of Neurological Disease, was awarded the Barancik Prize in 2018 for her work understanding the role of fibrin-related nerve damage in MS and designing potential therapies to prevent neurodegeneration. Dr. Dwight Bergles, of Johns Hopkins University, received the Barancik Prize in 2020 in recognition of his pioneering research in understanding the brain cells involved in myelin repair. Dr. Ruth Ann Marrie, of the University of Manitoba, is the 2022 recipient of the Barancik Prize in recognition of her groundbreaking contributions to our understanding of MS. We have a lot to talk about! Are you ready for RealTalk MS??! About the Barancik Prize Conversations  :18 Dr. Katerina Akassoglou  2:03 Dr. Dwight Bergles  10:00 Dr. Ruth Ann Marrie  20:58 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/barancik2 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com Join the RealTalk MS Facebook Group https://facebook.com/groups/realtalkms Download the RealTalk MS App for iOS Devices https://itunes.apple.com/us/app/realtalk-ms/id1436917200 Download the RealTalk MS App for Android Deviceshttps://play.google.com/store/apps/details?id=tv.wizzard.android.realtalk Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Bonus Episode: Barancik Prize Conversations -- Part 2 Guests: Dr. Katerina Akassoglou, Dr. Dwight Bergles, and Dr. Ruth Ann Marrie Tags: MS, MultipleSclerosis, MSResearch, MSSociety, RealTalkMS Privacy Policy

We're back this week with Seth Shipman from the Gladstone Institutes and the University of California, San Francisco. Seth has built molecular recording devices that can record data within living cells. He even used these methods to re-create one of the first movies put to film. This work has clear technological implications and is also providing insights into phage biology.

With a tangle of siloed systems and inefficient paper-based processes, Gladstone Institutes was looking to modernize its technology to better sustain its mission of overcoming unsolved diseases of the brain, heart, and immune system. We talked with Scott Pegg, Gladstone's CIO, and Derek Sharp at Avaap, to learn more. https://blog.workday.com/en-us/2023/workday-podcast-gladstones-journey-frankensteins-monster-successful-digital-transformation.html

Today, we have Seo Yeon Yoon, Research Scientist at Gladstone Institutes. She is an avid researcher passionate about bringing diverse talent and ideas together to innovate solutions that overcome incurable diseases. She was also recently named to the Poets and Quants 2022 list of Best & Brightest Executive MBAs.Seo Yeon is originally from Jeonju City, South Korea, a mid-small town that didn't have a lot of people from other countries or cultures. Her parents sent her and her sister to Canada as international students to study and be exposed to a world with many people from different ethnicities, races, and cultures. In this episode, Seo Yeon talked about her experiences as an international student, how she ended up in Berkeley as an undergrad, and why she chose to study Biology.She also shared her career at Gladstone Institutes, why she pursued her MBA later in her career, and her experiences at Haas. She also shared what made her start using her Korean name once again and why it was one of her impactful decisions.Episode Quotes:One of the lessons she learned as an international studentI think, looking back, it was really important that I had that much exposure to this bigger world with people that just didn't really think like me or even talk like me. But they were just really kind and really good people with really good hearts. And I always kept that with me as a life lesson that, wherever I go, that's something that I do have to keep in mind that I also have to extend as a friend and as a colleague in any places that I work.On her MBA applicationI went through the application process and tried to be as authentic as possible about who I was and why I really wanted to come to Haas. And while it was stressful, it just felt relatively good. It didn't really feel like it was an extra chore, per se. It was hard, but it wasn't something I was dragging myself into because I still wasn't sure about something. It was definitely a really good process to go through. And, of course, I was very, very happy to find out that all that effort and bidding on myself like that ended up very, fortunately, being a success. It was really wonderful.Why she started using her Korean nameI was thinking about how my parents named me. They didn't just name me just out of a whim or just out of nothing. They really had thought about it carefully about what they wanted to name their first child as. And my entire name is really, in and of itself, a form of a person, a woman my parents wanted me to be.And so, when I started to piece all of these puzzles together, I began to realize that, am I really doing justice to myself and also to the people that I love? That I will be sticking with an English name when it doesn't make anybody comfortable? And, first and foremost, it didn't make me comfortable.And so, I think that series of internal questioning and meditation and just, really, self-discovery process really got me to think about what is the easiest and also the most forefront thing on action can I really take to start on that discovery path. And the first thing was, really, the name.Show Links:LinkedInSupport this podcast at — https://redcircle.com/onehaas/donations

This week, please join author Keith Channon as he discusses the article "Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke-National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Oh, Greg, today's feature paper, something that's really been discussed a lot in the press and in lay public as well, the risk of myocarditis following sequential doses of the COVID-19 vaccine and SARS-CoV-2 infection by age and sex. Everyone's going to want to tune into that one. But before we get there, shall we go through some of the key papers in today's issue? Dr. Greg Hundley: You bet, Carolyn. How about if I go first? Dr. Carolyn Lam: Please. Dr. Greg Hundley: So Carolyn, this first manuscript involves the world of machine learning and ECG interpretation. And as you know, novel targeted treatments increase the need for prompt hypertrophic cardiomyopathy detection; however, it's low prevalence, 0.5%, and resemblance to common diseases really present challenges. So Carolyn, these authors, led by Dr. Rahul Deo from Brigham and Women's Hospital, sought to develop machine learning models to detect hypertrophic cardiomyopathy and differentiate it from other cardiac conditions using EKGs and echocardiograms with a robust generalizability across multiple cohorts. So Carolyn, what did they do? They used single-institution hypertrophic cardiomyopathy EKG models that were then trained and validated on data from three academic medical centers in the United States and Japan using a federated learning approach, which enables training on distributed data without data sharing. Models were validated on held out test sets for each institution and from a fourth academic medical center and were further evaluated for discrimination of hypertrophic cardiomyopathy from aortic stenosis, long-standing hypertension, and cardiac amyloidosis. And then finally, automated detection was compared to manual interpretation by three cardiologists on a data set with a realistic hypertrophic cardiomyopathy prevalence. Dr. Carolyn Lam: Wow, incredible. So what were the results? Dr. Greg Hundley: Right, Carolyn. So the authors identified 74,476 EKGs for 56,129 patients and 8,392 echocardiograms for 6,825 patients across the four academic medical centers. Now, while ECG models trained on data from each institution displayed excellent discrimination of hypertrophic cardiomyopathy on internal test data, the generalizability was limited, most notably for a model trained in Japan and then subsequently tested in the United States. Now, however, when trained in a federated manner, discrimination of hypertrophic cardiomyopathy was excellent across all institutions, including for phenotypic subgroups. The models further discriminated hypertrophic cardiomyopathy from hypertension, aortic stenosis, and cardiac amyloid. Analysis of ECG and echocardiography paired data from 11,823 patients from an external institution indicated a higher sensitivity of automated HCM detection at a given positive predictive value compared with cardiologists. So Carolyn, in conclusion, federated learning improved the generalizability of models that use EKGs and echocardiograms to detect and differentiate hypertrophic cardiomyopathy from other causes of left ventricular hypertrophy compared to training within a single institution. It will be really interesting to see the future applicability of these methods. Dr. Carolyn Lam: Oh, I'm such a fan of this work. Awesome. Thank you, Greg. My paper, it's a preclinical paper that uncovers a novel mechanism through which GATA4 mutations can lead to heart disease. Dr. Greg Hundley: All right, Carolyn, no quiz this time, I'm just coming right out. I'm reversing the question on the teacher. Tell me, what is GATA4? Dr. Carolyn Lam: I'm glad you asked, Greg. GATA4 is a zinc finger-containing DNA binding transcription factor essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Now, in today's paper, authors led by Dr. Srivastava from Gladstone Institutes in San Francisco, California, showed that GATA4 regulated cell-type-specific splicing through direct interaction with RNA and the spliceosome in human-induced pluripotent stem cell-derived cardiac progenitors. An unbiased search for GATA4 interacting proteins in these human iPS cells revealed interaction with many members of the spliceosome complex. GATA4 also bound to pre-messenger RNAs in a sequence-specific manner that resulted in generation of alternatively spliced isoforms in human iPS cells. Many of these GATA4-dependent isoforms had distinct functional properties illustrating the importance of the splicing regulation to cardiac function. Dr. Greg Hundley: Wow, Carolyn, another really interesting study from the world of preclinical science. So what's the take home message here? Dr. Carolyn Lam: So these results essentially uncover a previously unrecognized function for GATA4 in regulating alternative splicing through direct RNA interaction. Several genes that have splicing regulated by GATA4 have functional consequences and many are associated with dilated cardiomyopathy, thus suggesting a novel role for GATA4 in achieving the necessary cardiac proteome in normal and stress-responsive conditions. Dr. Greg Hundley: Very nice, Carolyn, wow. Well, my next paper comes to us from back in the world of clinical science and it's from Professor Bertrand Cariou from L'institut du Thorax in Inserm UMR1087. So Carolyn, only a few genes causally related to plasma LDL-C levels have been identified so far, and only one, ANGPTL3, has been causally related to combined hypocholesterolemia. In this study, the authors aim to elucidate the genetic origin of an unexplained combined hypocholesterolemia inherited in four generations of a French family and used next generation sequencing and identified a novel dominant rare variant in the LIPC gene encoding for hepatic lipase, which co-segregates with the phenotype. They characterize the impact of this LIPC-E97G variant on circulating lipid and lipoprotein levels in family members using nuclear magnetic resonance based lipoprotein profiling and lipids. Dr. Carolyn Lam: Wow, what an interesting approach to study patients and families with hypocholesterolemia for once instead of hyper. Interesting. So what did they find? Dr. Greg Hundley: Right, Carolyn. So the investigative team found that this unique LIPC-E97G variant specifically increases the phospholipase activity of hepatic lipase without affecting triglyceride lipase activity. And second, the hypocholesterolemic phenotype related to LIPC-E97G variant is due to an increased clearance of cholesterol within triglyceride-rich lipoprotein remnants predominantly by extrahepatic tissues. Dr. Carolyn Lam: Wow, so what are the implications? Dr. Greg Hundley: Right, Carolyn. So the novel gain of function variant in LIPC potentially represents the second cause of familial combined hypocholesterolemia after loss of function variants in ANGPTL3. And second, this study highlights an unexpected and critical role of the phospholipase activity of hepatic lipase encoded by LIPC in LDL-C metabolism and identifies it as a potential novel drug target. And then finally, Carolyn, additional data, I think, are warranted to clarify the impact of LIPC-E97G-related combined hypocholesterolemia on atherosclerosis and atherosclerotic cardiovascular disease due to the occurrence of documented coronary stenosis and evolutive carotid atherosclerosis in index cases. Dr. Carolyn Lam: Oh, very, very interesting. Thanks, Greg. Well, let's wrap up with the discussion of what else is in today's issue. There's an In Depth paper by Dr. Hadley on protecting cardiovascular health from wildfire smoke. There's also a Research Letter by Dr. Mevorach on myocarditis after BNT162b2 COVID-19 third booster vaccine in Israel. Dr. Greg Hundley: Right, Carolyn. And then I've got an exchange of letters from Professors Condello and Doenst regarding the article Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis from the REMOVE study: Results From a Multicenter Randomized Controlled Trial. Well, how about we get on to that feature discussion and learn a little bit more about COVID-19 vaccine and SARS-CoV-2 infection. Dr. Carolyn Lam: Let's go, Greg, thanks. Dr. Greg Hundley: Listeners, welcome to this September 6th feature discussion. And with us today, very interesting topic pertaining to vaccination for SARS-CoV-2 virus prevention. And we have with us Dr. Keith Channon from Oxford, England, to discuss this very interesting paper. Well, Keith, welcome. I wanted to start by asking you, can you describe for us a little the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Keith Channon: Thanks, Greg, for the opportunity to join you in this interesting conversation today. A group of cardiologists in the UK based at the University of Oxford, and principally at the University of Edinburgh, have been interested in the question as to whether COVID infection and/or COVID vaccination might lead to a higher incidence of myocarditis. And this is a topic that has been the subject of previous publications in the field. And the provocation for us undertaking this study is that those previous studies have tended to be relatively small, and they've also not been able to necessarily test the details, time association, between myocarditis occurring in relation to sequential doses of vaccination. And that's important because, of course, we're now all receiving sequential doses of booster vaccines, and also those vaccines are often delivered, different vaccine types to different people in different countries. So we wanted to test whether there does appear to be a significant association between the occurrence of myocarditis and both COVID infection and the sequential different COVID vaccinations. Dr. Greg Hundley: Very nice. So Keith, can you describe for us, what study population did you enroll for this initiative? And then also, what was your study design? Dr. Keith Channon: Thank you. So, one of the really exciting things about this type of study and probably what makes it unique is that in countries with healthcare system, like that in the UK, which is the National Health Service, and universities, such as the University of Oxford and the University of Edinburgh, where there are very strong academic links between researchers and the National Health Service, we've been able to leverage an enormous data set, which is almost 43 million people in the UK who underwent vaccination against COVID-19. And rather than having to follow up 43 million people as part of a research study, we were able to take advantage of National Health Service centralized coded hospital records, number one. Number two, we took advantage of the UK's national database on COVID vaccination. And number three, we were able to look at hospital outcomes and also COVID testing. So we were able to put together those three data sets for us to understand who developed COVID infection, who received COVID vaccination, and if so, which vaccine and when, and who then was admitted to hospital with a coded diagnosis of myocarditis. And in 43 million people, even though myocarditis is a very uncommon outcome, there were sufficient cases in that very large population to draw statistically meaningful conclusions. I think that the UK is probably one of the few countries where this type of research can be done. And academic organizations, like our universities, the National Health Service, and also cardiovascular research funders, such as the British Heart Foundation, have put in a lot of resource and effort into giving us those capabilities to answer questions like this, and it's turned out to be a very powerful capability. Dr. Greg Hundley: Very nice. And so Keith, can you describe for us your study results? Dr. Keith Channon: So the study looked at a large 43 million people approximately over a period of time during the early to mid-phase of the COVID pandemic and looked at the likelihood that people would be diagnosed with myocarditis following either vaccination or COVID test positive. And we compared that likelihood with the likelihood of myocarditis occurring outside of those periods; because, of course, myocarditis occurs reasonably commonly in the general population. So this is another powerful aspect of the study design. It has a curated approach to look at the incidence of myocarditis in the 28 days after either vaccination or COVID infection, and it corrects, or it controls for that relative to the incidence of myocarditis outside of those sampling periods. And what we found simply is that there is indeed, as previous studies have shown, a small but significant association between receiving a COVID-19 vaccine and being diagnosed with myocarditis in the following 28 days. However, in the population as a whole, the risk of myocarditis after vaccination is substantially lower than the risk of developing myocarditis after COVID infection, and I think that's an important finding. When we looked at subgroups, which is interesting, we found that the highest risk of developing myocarditis was in men less than age 40, so younger men, and that was one finding. And also, there did seem to be some differences in the risk of myocarditis occurring after different sequential vaccine doses. Dr. Greg Hundley: Keith, just a quick clarification point, what vaccines did you examine? Dr. Keith Channon: So in the UK, the three vaccines that have been largely used of the AstraZeneca Oxford viral vaccine, ChAdOx1, which was of course introduced very early in the UK, along with the Pfizer mRNA vaccine, and then laterally, Moderna vaccine, which of course in the UK was brought in rather later. And I think that's interesting because, as we can go on and discuss, there do appear to be some possible differences between those vaccines in terms of the likelihood of being diagnosed with myocarditis afterwards. But of course, even our experiment in 43 million people is not a perfect design because it's an observational study, and the periods in the pandemic when people were receiving principally the first two vaccines, which were by far the most numerous, was a different period in the natural history of the pandemic than when we started administering Moderna. So it is important to recognize that it was not a prospectively controlled randomized trial of different vaccines; it was an observational study of pretty much a whole country and how it responded to the implementation of those different vaccines, which were all given to different people at different times of the pandemic. And of course, different times of the pandemic means that many different people will have already had a COVID infection and then gone on to have a booster or third vaccination. So, if you like, the immunological landscape in which these different vaccines were given in this very large population will have been different. Dr. Greg Hundley: Right. So I understand there are differences in timing, great point, but did you see any differences in the occurrence of myocarditis relative to either of the mRNA vaccines versus the adenovirus vaccine? Dr. Keith Channon: Yeah, we did. What we found is that, interestingly, there did appear to be a higher likelihood of being diagnosed with myocarditis in the 28 days after the mRNA-1273 vaccine, Moderna vaccine, and that was particularly, as I've already said, in men younger than the age of 40 years. I should say again, of course, that vaccine was given to the smallest number of people in the UK and it also tended to be rolled out later, so it was the second or third dose of the vaccine where that signal was most seen. But again, the second and third dose was by definition typically the booster vaccine later on in the pandemic. But that's what we found. We did find these interesting differences. The incidence of myocarditis was increased after all of the vaccine doses compared with the period when people had not received a vaccine, but this was a very modest increase for most of the vaccines; but for the mRNA vaccines, particularly Moderna, it seemed to be more strikingly increased in the 28 days after the second or third dose of the vaccine. So I guess the message from that result is that there do seem to be these intriguing differences, both in the response to different COVID vaccines, either viral or mRNA or indeed even different types of mRNA vaccine, and possibly after the different dose of vaccines. In other words, after second or third sequential doses. Dr. Greg Hundley: And Keith, you mentioned a few minutes ago that you also had an opportunity to examine situations where maybe a patient had a vaccine and then subsequently contracted COVID, or vice versa, maybe they had had COVID and then later on had a vaccine, did you find any differences in the incidence of myocarditis in those situations as opposed to, perhaps, patients that really never had a documented episode of a COVID infection and then always had received the two vaccines and the booster dose? Dr. Keith Channon: Yeah, that's a harder question and is less powerfully addressed by our study, even though we were able to temporally control for that. Previous COVID infection did not preclude the risk of myocarditis after subsequent vaccine doses, but it wasn't a big enough signal to be able to give much detail over the relative risk between... Because if you think of the permutations of COVID infection plus or minus three vaccines, there's a lot of different sequential steps there, but having had COVID first doesn't prevent this small but significant signal; having a vaccine before you then get COVID infection does reduce your risk of myocarditis along with pretty much all other COVID complications. So I think that's a really important public health message here and indeed the overarching finding of our study, which you could argue is the least exciting one but perhaps the most important, which is that you have a higher likelihood of suffering with myocarditis after COVID infection compared with after a COVID vaccination. And if you have COVID vaccination, in general, your risk of myocarditis is lower, obviously your risk of COVID infection is lower, and your risk of getting myocarditis after that COVID infection, should you still get one is also lower. So I think these are very intriguing, interesting findings that might make us think about mechanism and vaccine policy, but ultimately there are very strong endorsement of getting vaccinated to prevent the consequences of COVID-19. Dr. Greg Hundley: Excellent point. And then, Keith, just quickly, next study that maybe your group is considering in this space with this large database? Dr. Keith Channon: Yes. Well, I think there are two aspects to the study. Our group, which, as I've said, focuses mainly on large epidemiological data sets, having established this infrastructure in the UK led by universities like Oxford and Edinburgh and funded by the British Heart Foundation and others, means that we now have this infrastructure. So the surveillance and the data collection and the analysis is ongoing and we'll be able to add more cases and more power and more data, and there will be other studies that we can look at. Second, I think there are some really quite interesting mechanistic studies that could be done based on these provocative findings to try to understand which different types of vaccines and, indeed, the immune responses which those vaccines generate. How are they linked to myocarditis and, indeed, to other cardiac and even other organ complications from COVID-19? And there are ongoing studies in the UK and elsewhere in the world that are very much focused on looking at the organ-specific consequences of COVID infection in patients who've been vaccinated or not. For example, using detailed cardiac MRI to look at the heart and look for subclinical myocarditis and to correlate any evidence of subclinical myocarditis with the immune signature, both the antibody and the cellular immune response, in the blood from those patients. So I think what we're going to see here are enormous epidemiological studies with n=43 million, and we're also going to see more mechanistic experimental medicine immunology studies to try and tease out mechanism, and I think to understand two things. One is how to protect ourselves best against COVID-19, and what are the best vaccines and how best to use them. And second, if we can learn something about the mechanisms of myocarditis along the way, that's a really useful bonus that's come out of this pandemic. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Keith Channon for bringing us this very interesting article from Great Britain highlighting that, overall, the risk of myocarditis is greater following SARS-CoV-2 infection as opposed to a COVID-19 vaccination, and even really remains modest following sequential doses, including the booster dose of some of the mRNA vaccines. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is a copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit AHAjournals.org.

A new generation of biologists is pushing the limits of third-generation sequencing, furthering the technology's development and defining new applications to answer biology's most pressing questions. This is the express goal for the lab of Vijay Ramani, assistant professor at UCSF in the department of Biophysics and Biochemistry. Vijay also has an appointment in the Institute of Data Science and Biotechnology at the Gladstone Institute, and in 2019 he was named to the Forbes 30 under 30 rising stars in healthcare list.

Dr. Arye Elfenbein, MD, PhD, is the Co-Founder of Wildtype (https://www.wildtypefoods.com/), a biotechnology company which produces cultured seafood (with a focus on cultivated Pacific salmon) from fish cells, sustainably and cost effectively, with the nutritional benefits, but without common contaminants such as mercury, microplastics, antibiotics, or pesticides, and without relying on commercial fishing or fish farming. Born in Israel and raised in Australia, Dr. Elfenbein combines his deep passion for medicine and unique childhood connection to the ocean to fuel Wildtype's health and environmental mission. After studying at Dartmouth and Kyoto University, attaining a PhD and MD, Dr. Elfenbein began his residency at Yale where he first trained in Internal Medicine before completing training in Cardiology. After residency, he moved to San Francisco to work with Professor Dr. Deepak Srivastava at the revered Gladstone Institutes / UCSF, also known for being the scientific homes of Nobel laureates Dr. Shinya Yamanaka (iPs cells) and Dr. Jennifer Doudna (CRISPR). During his time at the Gladstone Institutes, Dr. Elfenbein's research focused on cardiac regeneration following heart attacks. This research inspired him to apply the principles of stem cell biology beyond medicine, and to address the growing problems in our food system. When away from Wildtype, Dr. Elfenbein continues to work as a cardiologist with a focus on critical care, lending his expertise and passion for patient care to the ICU.

My guest this week is someone I have wanted to interview on my podcast since the FIRST SEASON. This someone is not only a groundbreaking researcher and scientist, he is also my dear friend, Dr. Alexander Marson.  Alex is the Director of Gladstone-UCSF Institute of Genomic Immunology, a senior investigator at Gladstone Institute, and an Associate Professor in the Departments of Medicine and Microbiology and Immunology at UCSF.  Alex is interested in how DNA controls the behavior of cells in the human immune system. He and his team are using the power of CRISPR technology to genetically engineer cells to fight cancer, autoimmune diseases, and infectious diseases. My intention for recording this particular conversation was to get Alex's take on communicating complex messages in a more accessible way. It's something the scientific community is really wrestling with these days, perhaps now more than ever:  How do you communicate complicated and immense topics in a way that is repeatable and interesting? How do we approach critical information, currently understood by only a few, to make it accessible to the rest of us? This is also a conversation about the alchemy that happens when the right people make contact at the right moment, and something new is born.  Pour that beverage, or lace up your sneakers and leash up that hound. Because you are gonna love this one.

Sally and Kayla welcome Dr. Serah Kang to discuss her experience applying for academic postdoc positions and industry roles. After completing her PhD, Serah spent two years as a postdoctoral fellow at the Gladstone Institute and now is a senior scientist at Genetech. Serah also discusses how her applications and job decisions were impacted by transhood and how employers can attract and support trans scientists. This is the first in a new series about finding your path after getting your PhD! Stay tuned!! 

We talk about hybrid immunity against COVID and why it is a good thing. We unpack, how Netflix's queer twitter channel tried to react to their own company's controversy, and how we feel about it!  Plus, Brandon Farbstein joins us to talk about accepting yourself, and so much more. Let's go there!    Special guests: Dr. Warner Greene - Virologist at the Gladstone Institutes in San Francisco. Brandon Farbstein -Gen Z world changer, motivational speaker, and author of “A Kids Book About Love”. See omnystudio.com/listener for privacy information.

Maple recounts her experience going through her first and early second trimester during the height of COVID in San Francisco. She works in finance and her partner is a researcher at the Gladstone Institute.

While attention has shifted to mass vaccinations, the Gladstone Institutes in San Francisco remain focused on finding therapies to treat COVID-19 and defeat future Coronaviruses.

Does Keto Cause Anti Aging?https://rockthatketo.com/anti-aging-from-keto/ (https://rockthatketo.com/anti-aging-from-keto) What does anti aging mean? That you will stay 25 years old forever? Of course not. You are going to age one way or the other. But what about slowing down the aging process at the cellular level.  In real life, it means your health will be extended much further into older age. Being alive is different than LIVING.  Just slogging along while you feel terrible is not really a good way to go about life. Anti Aging means to slow the aging process. The more your cells age, the less they work well.  Keto has anti aging properties on several layers. Well, everyone is different, but in general, the keto diet can create an environment that causes the body to create anti aging chemicals. Younger and skinny? That’s a great combination.  According to studies, there is a natural body chemical called B-hydroxybutyrate. It protects your cells from genetic damage and internal stress.  This happens because it blocks an enzyme.  This enzyme prevents certain good genes from becoming active.  We want these good genes to become active. When these helpful genes become active, they protect the cells from aging.  Yes, I’m simplifying it a lot, but really that’s what you need to know.  Plus the fact that going keto may help prevent a bunch of diseases, including heart and brain problems, like dementia. It’s a Serious StudyThe author of the study,  Dr Katerina Akassoglou works at the Gladstone Institute for Virology and Immunology in San Francisco.    In the study was the question: “Is Anti Aging from Keto possible?” She said: 'The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injury.’ '[These] diseases afflict millions and there are few treatment options.'  I’m not a doctor and I don’t make claims. These are from the Doctor who did the study. We know from lots of research, that when we lower our carbs, and only include ‘healthy’ carbs, our body goes through a big shift in how it burns and stores fat. That process forces the body to secrete B-hydroxybutyrate. Then good things start happening, in addition to losing weight.  There’s Another Way To Activate ItFasting also releases this same chemical, which researchers have known for years.  As you may know, intermittent fasting is one of the things we recommend a lot. I have it built into my daily routine. I don’t eat until lunch time every day. So I have a built-in fast from dinner the night before until lunch, which I usually eat between noon and 1pm. It’s simple, helps me feel better, and keeps the weight steady. It is also anti aging.  Anti aging from keto? Apparently yes.  If the keto diet is helping prevent degenerative diseases, it is helping people live happier. Living a long time but being diseased and miserable is not a great bargain. Living long and healthy? That’s a deal I’m interested in. If you like these tips and would like to get more tips, endless recipes, and lots of inspiration, then come to our free website and sign up for our mailing list.https://rockthatketo.com/ ( )https://rockthatketo.com/. (https://rockthatketo.com/)  Act! Don’t React! Have a Happy, Healthy Day Livtar

The COVID-19 pandemic, which began in early 2019, has had significantly negative consequences for individuals, families and communities around the world, with huge economic and political effects. Short-term strategies have involved sheltering in place and social distancing, rigorous and frequent hand washing, and the disciplined use of masks. We now have reached a stage in the pandemic when vaccines are bring rolled out in the United States and globally, initially for “at risk” populations. There is much confusion arising from conflicting information about the new vaccines. There are questions related to what we know about the vaccines (and how we know it), and what we don’t know (and how and when we will know more). To address these questions, two leading virologists will be in conversation with the chair of the Health and Medicine Forum at The Commonwealth Club of California. Dr. Melanie Ott and Dr. Warner Greene from Gladstone Institutes talk with Dr. Robert Lee Kilpatrick, to help the public understand COVID-19 vaccine options better. Meet the Speakers Melanie Ott, M.D., Ph.D., has been the director of the Gladstone Institute of Virology since 2020, and a senior investigator at Gladstone Institutes. She is also a professor of medicine at University of California, San Francisco (UCSF). Since the outbreak of the coronavirus pandemic, she pivoted the focus of her team to work on SARS-CoV-2, the virus that causes COVID-19. Ott is a member of the Association of American Physicians, and a Fellow of the American Academy of Microbiology. She is also an expert contributor to the COVID Collaborative, a bipartisan group of national experts and institutions that helps shape state and local efforts against the pandemic. Warner Greene, M.D., Ph.D., is the director of the The Michael Hulton—Gladstone Center for HIV Cure Research, senior investigator, and Nick and Sue Hellmann Distinguished Professor of Translational Medicine at Gladstone Institutes. He is the founding and emeritus director of Gladstone Institute of Virology and Immunology. Greene is also professor of medicine, microbiology and of immunology at UCSF. He is also a member of the Institute of Medicine of the National Academies and a fellow of the American Academy Arts and Sciences. He also serves as co-director of the UCSF-Gladstone Center for AIDS Research, and he has served as councilor and president of the Association of American Physicians. Robert Lee Kilpatrick, Ph.D., is the chair of the Health and Medicine Member-Led Forum at The Commonwealth Club of California, general advisor to Berkeley SkyDeck incubator and accelerator, advisor to the Columbia University Master of Science Program in Bioethics, and CEO of Health Innovation for People, Inc. (HIP). MLF ORGANIZER Robert Lee Kilpatrick NOTES MLF: Health & Medicine In association with Gladstone Institutes. SPEAKERS Warner Greene M.D., Ph.D., Director, Gladstone Center for HIV Cure Research; Senior Investigator and Nick and Sue Hellmann Distinguished Professor of Translational Medicine at Gladstone Institutes; Professor of Medicine, Microbiology and of Immunology, UCSF Melanie Ott M.D., Ph.D., Director, Gladstone Institute of Virology; Senior Investigator, Gladstone Institutes; Professor of Medicine, University of California, San Francisco Robert Lee Kilpatrick Ph.D. Chair, Health and Medicine MLF; General Advisor, Berkeley SkyDeck incubator and Accelerator; Advisor, Columbia University Master of Science Program in Bioethics; CEO, Health Innovation for People, Inc. (HIP) In response to the COVID-19 pandemic, we are currently hosting all of our live programming via YouTube live stream. This program was recorded via video conference on February 10th, 2021 by the Commonwealth Club of California.

The COVID-19 pandemic, which began in early 2019, has had significantly negative consequences for individuals, families and communities around the world, with huge economic and political effects. Short-term strategies have involved sheltering in place and social distancing, rigorous and frequent hand washing, and the disciplined use of masks. We now have reached a stage in the pandemic when vaccines are bring rolled out in the United States and globally, initially for “at risk” populations. There is much confusion arising from conflicting information about the new vaccines. There are questions related to what we know about the vaccines (and how we know it), and what we don't know (and how and when we will know more). To address these questions, two leading virologists will be in conversation with the chair of the Health and Medicine Forum at The Commonwealth Club of California. Dr. Melanie Ott and Dr. Warner Greene from Gladstone Institutes talk with Dr. Robert Lee Kilpatrick, to help the public understand COVID-19 vaccine options better. Meet the Speakers Melanie Ott, M.D., Ph.D., has been the director of the Gladstone Institute of Virology since 2020, and a senior investigator at Gladstone Institutes. She is also a professor of medicine at University of California, San Francisco (UCSF). Since the outbreak of the coronavirus pandemic, she pivoted the focus of her team to work on SARS-CoV-2, the virus that causes COVID-19. Ott is a member of the Association of American Physicians, and a Fellow of the American Academy of Microbiology. She is also an expert contributor to the COVID Collaborative, a bipartisan group of national experts and institutions that helps shape state and local efforts against the pandemic. Warner Greene, M.D., Ph.D., is the director of the The Michael Hulton—Gladstone Center for HIV Cure Research, senior investigator, and Nick and Sue Hellmann Distinguished Professor of Translational Medicine at Gladstone Institutes. He is the founding and emeritus director of Gladstone Institute of Virology and Immunology. Greene is also professor of medicine, microbiology and of immunology at UCSF. He is also a member of the Institute of Medicine of the National Academies and a fellow of the American Academy Arts and Sciences. He also serves as co-director of the UCSF-Gladstone Center for AIDS Research, and he has served as councilor and president of the Association of American Physicians. Robert Lee Kilpatrick, Ph.D., is the chair of the Health and Medicine Member-Led Forum at The Commonwealth Club of California, general advisor to Berkeley SkyDeck incubator and accelerator, advisor to the Columbia University Master of Science Program in Bioethics, and CEO of Health Innovation for People, Inc. (HIP). MLF ORGANIZER Robert Lee Kilpatrick NOTES MLF: Health & Medicine In association with Gladstone Institutes. SPEAKERS Warner Greene M.D., Ph.D., Director, Gladstone Center for HIV Cure Research; Senior Investigator and Nick and Sue Hellmann Distinguished Professor of Translational Medicine at Gladstone Institutes; Professor of Medicine, Microbiology and of Immunology, UCSF Melanie Ott M.D., Ph.D., Director, Gladstone Institute of Virology; Senior Investigator, Gladstone Institutes; Professor of Medicine, University of California, San Francisco Robert Lee Kilpatrick Ph.D. Chair, Health and Medicine MLF; General Advisor, Berkeley SkyDeck incubator and Accelerator; Advisor, Columbia University Master of Science Program in Bioethics; CEO, Health Innovation for People, Inc. (HIP) In response to the COVID-19 pandemic, we are currently hosting all of our live programming via YouTube live stream. This program was recorded via video conference on February 10th, 2021 by the Commonwealth Club of California. Learn more about your ad choices. Visit megaphone.fm/adchoices

This week's episode features author Adnan Kastrati and Associate Editor Dharam Kumbhani as they discuss ticagrelor or prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. TRANSCRIPT BELOW: Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your cohosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor and Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature Ticagrelor Prasmul in patients with ST segment elevation myocardial infarction undergoing primary PCI. More on that story later, though. How about we grab a cup of coffee and look at some of the other papers in the issue. Would you like to go first? Dr. Carolyn Lam: I would. And actually, I'm going to talk about two papers and they're all about BET, BET or promo domain, an extra terminal epigenetic reta proteins. And in particular, this one called BRD4. Now these proteins have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small molecular BET protein inhibitors, such as JQ1 have demonstrated efficacy in reversing cardiac hypertrophy and heart failure in preclinical models. Yet genetic studies elucidating the biology of BET proteins in the heart have not been conducted. Well, at least until this week's issue where we have not one, but two papers, both elegantly using mouse genetic studies. Dr. Carolyn Lam: In the first from Dr. Srivastava from Gladstone Institute of Cardiovascular Disease in San Francisco and Dr. Jain from Perlman School of Medicine in Philadelphia and their colleagues, they found that BRD4, that particular BET epigenetic reader protein, forms a transcriptional regulatory module with GATA4, a lineage determining transcription factor in cardiomyocytes. This BRD4 GATA4 module was a critical orchestrator of mitochondrial bioenergetics in the adult heart. Dr. Greg Hundley: Well Carolyn, that is a wonderful summary. What are the clinical implications? Dr. Carolyn Lam: Identification of this new BRD4 interaction partner, such as GATA4 could provide new insights into developing epigenetic based therapies for heart failure. And the second paper is from Dr. Joseph Hill and Thomas Gillette from University of Texas Southwestern Medical Center and their colleagues. And what they found was that BRD4 was essential to the maintenance of mitochondrial electron transport chain function via transcriptional regulation of a nuclear mitochondrial gene network. BRD4 heterozygous deletion resulted in delayed heart failure, whereas pharmacological BRD4 inhibition using JQ1 induced modest changes in mitochondrial genes suggesting potential cardiac toxicity in targeting BRD4 at baseline. Dr. Greg Hundley: So what does this mean for us clinically, Carolyn? Dr. Carolyn Lam: As more potent and specific inhibitors are developed targeting BRD4 for clinical settings in oncology and other diseases, we must carefully monitor bezel cardiac performance for functional and mitochondrial deterioration. Important clinical message there. Dr. Greg Hundley: Great job, Carolyn. Well, my first paper is entitled "An Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaques" And it comes to us from Dr. Tomas Neilan and his colleagues at the Mass General Hospital. The study was situated in a single academic medical center. And Carolyn in this paper, there are actually three studies described. First, there's a primary analysis that evaluated whether exposure to an immune checkpoint inhibitor during treatment for cancer was associated with atherosclerotic cardiovascular events among 2,842 patients versus 2,842 controls that were matched by age, a history of cardiovascular events and cancer type. Dr. Greg Hundley: In the second study, a case crossover analysis was performed with an at risk period defined as the two year period after, and the control period as the two year prior to treatment. The primary outcome was a composite of atherosclerotic cardiovascular events including myocardial infarction, coronary revascularization, and ischemic stroke. And secondary outcomes included the individual components of that primary outcome. Dr. Greg Hundley: Finally, in the third study in this paper, there's an imaging stub study of 40 individuals, and it looked at the rate of atherosclerotic plaque progression compared from before and after starting the immune checkpoint inhibitor. All study measures and outcomes were blindly adjudicated in this third study. Dr. Carolyn Lam: Wow, a three in one. That really sounds novel. So what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. In the matched cohort study, there was a three-fold higher risk for cardiovascular events after starting an immune checkpoint inhibitor. There was a similar increase in each of the individual components of the primary outcome. In the case crossover study, there was also an increase in cardiovascular events from 1.37 to 6.55 per hundred person years at the two year time point. Dr. Greg Hundley: And then lastly, Carolyn, in the imaging study, the rate of progression of total aortic plaque volume was three fold higher after immune checkpoint inhibitors from 2.1% per year to 6.7% per year after receiving these agents. The association between immune checkpoint inhibitor use and increased atherosclerotic plaque progression was attenuated with the concomitant use of statins or corticosteroids. Dr. Carolyn Lam: Wow, Greg. So I suppose what all this shows is that we need to be aware of the cardiovascular risk prior to, during and after treatment with immune checkpoint inhibitors and perhaps, you know, optimize these cardiovascular risk factors. Thank you, Greg. Dr. Greg Hundley: You bet. Well, Carolyn, my next paper is from Dr. George Vlachojannis from University Medical Center at Utrecht. These authors conducted a randomized control multi-center trial in the Netherlands enrolling STEMI patients planned to undergo primary PCI. Now patients were randomly allocated to receive in the ambulance before transfer a 60 milligram loading dose of Prasugrel, either being crushed or as integral tablets. The independent primary end points were thrombolysis in myocardial infarction, TIMI three flow in the infarct related artery at initial coronary angiography, and complete greater than they go to 70% ST segment resolution one hour post primary PCI. The safety end points were TIMI major and bleeding academic research consortium, or BARC, greater than three bleedings and secondary end points included platelet reactivity and ischemic outcomes. Dr. Carolyn Lam: Nice trial design. So what did they find? Dr. Greg Hundley: Well, Carolyn, a total of 727 patients were assigned to either crushed or integral tablets of Prasugrel. The median time from study treatment to wire crossing during primary PCI was 57 minutes, and the primary end point of TIMI three flow in the infarct related pre primary PCI artery occurred in 31% in the crushed group versus 32.7% in the integral group. No difference, P .064. Complete ST segment resolution one hour post primary PCI was present in 59.9% in the crush group and 57.3% in the integral group. Again, no difference, P equals .055. Platelet reactivity at the beginning of primary PCI measured as the P2Y12 reactivity unit, differed significantly between the groups. Crushed was 192 versus integral was 227 and the P value was less than 0.01. TIMI major and BARC greater than three bleeding occurred in 0% in the crushed group and 0.8% in the integral group and in 0.3% in the crushed group versus 1.1% in the integral group respectively. So there were no differences observed between groups regarding ischemic events at 30 days. Dr. Greg Hundley: So Carolyn, in conclusion, prehospital administration of crushed Prasugrel tablets does not improve TIMI three flow in the infarct related artery, pre primary PCI or complete SD segment resolution one hour post primary PCI in patients presenting with STEMI planned for primary PCI. Dr. Carolyn Lam: Interesting and interesting stuff with platelet reactivity and bleeding. Thank you, Greg. Well, there are other papers in today's issue. There's an in-depth paper by Dr. Katsanos on stroke prevention in atrial fibrillation, looking forward. There's a research letter by Dr. Berger on myocardial injury in adults hospitalized with COVID-19 and another by Dr. Hacker on again, immune checkpoint inhibitor therapy and how that induces inflammatory activity in large arteries. Dr. Greg Hundley: Well, Carolyn, I've got a couple other papers to talk about in this issue. There's a On My Mind piece from Dr. deFilippi entitled "Navigating Testing for COVID-19." There's a Perspective from Dr. Ridker entitled "Equipoise Trust and the Need for Cardiologists to Randomize Patients into Anticoagulation Trials in the Time of COVID." There's an ECG challenge from Dr. Arias entitled, "A Paced Tachycardia." And then finally, there's an exchange of letters from Drs. Liu regarding a prior publication entitled "Branched-Chain Amino Acid Catabolism Promotes Thrombosis Risk by Enhancing Tropomodulin-3 Propionylation in Platelets." Well, Carolyn, how about we get to the world of anti-platelet therapy, ticagrelor prasugrel in patients with ST segment elevation myocardial infarction, shall we? Dr. Carolyn Lam: Yes, let's go Greg. Dr. Greg Hundley: Well welcome, listeners, to our featured discussion today on this December 15, and we are going to learn and discuss a little more, a paper pertaining to ticagrelor versus prasugrel in patients with ST segment elevation myocardial infarction. And our lead author today is Adnan Kastrati from Deutsches Heart center in Munich. And we also have our own Associate Editor, Dr. Dharam Kumbhani from UT Southwestern in Dallas. Welcome, gentlemen. Adnan, maybe I'll start with you. Could you tell us a little bit about the background related to this article and what was the hypothesis that you wanted to address? Dr. Adnan Kastrati: First of all, thank you very much for having me here to share with you some thoughts. Thank you, Dharam, for handling our paper in Circulation. We are very honored to have it published there. About these are the ISAR REACT-5 series of studies dedicated to optimizing the antiplatelet therapy in patients and anticoagulant therapy in patients with acute and chronic coronary syndromes, mostly who are undergoing a PCI procedure. We started to think about that study immediately after the publication of the platelet trial. We showed the superiority of prasugrel in patients with acute coronary syndromes. These were the two new ADP receptor antagonists at the time. And so as a physician, we are interested to know which of them was better because there was no direct comparison. And so that's why we decided to have an open-label trial randomized. Most of the centers were situated in Germany. Two centers were situated in Italy. The private end point was adopted to the private end point of the trials in this skill. Only one difference was there, instead of cardiovascular death, we put all cause death in the primary end point. Why? Because all cause death may also reflect the gradient end bleeding between the two drugs. We wanted to have a more integrative endpoint in this sense. So it was a combination of all cause death, myocardial infarction, and stroke. Dr. Adnan Kastrati: It was a one year followup study. The study had two groups of steady patients, which was about 40% of the patients, included in the multicentral trial. And what we found in this trial, it was the same results as it was found in the whole trial. The advantages seen for prasugrel was present here also. Although we lost the significance in the evaluation of the primary endpoint. It was a 31% increase or 24% decrease with prasugrel in that sense. But otherwise everything was in the same direction as in the whole trial. And if you look also in the components of the primary end point…, you have the chance to see that numerically, it was the same trend for all components. Although the trial was not powered for going to evaluate the component of the prime end point. This was the main result. Dr. Greg Hundley: It sounds like you had 1,653 patients with STEMI randomized to receive ticagrelor or prasugrel and 10% experienced the primary end point in the ticagrelor group, but only 7.9% in the prasugrel group. But the P value was only .10. We saw trends toward favoring prasugrel rather than sort of a definitive difference. Is that a correct summary? Dr. Adnan Kastrati: Yes, it is a correct summary. I would say this group of patients is the most interesting subgroup of patients in ISAR 5 trial. Why? Because the pretreatment strategy is the same. Because there have been a lot of discussions about non-S-segment segment elevation acute myocardial infarction due to the difference in pretreatment. Although it was intentional, some people felt it's different and they said you have two different strategies there. In the STEMI subgroup, the pretreatment strategy was the same, so it was a head to head comparison of two drugs, even according to the same strategy. This is one. Dr. Adnan Kastrati: Second, you have to look back at the trials in the same field…Both these trials, if you look closely to the results of for STEMI patients, both of these trials haven't shown a significant result for the STEMI subgroup. For plateau it was a P value of 007 and for tritan it was a P value of 0014 only. Why? Because in the tritan it was very specific. They included also patients after fever analyzes and the significance came only from the comparison of tritan in this group, not in the primary PCI group. In the plateau and ISAR-5 we excluded these patients. Dr. Greg Hundley: Dharam, we're going to turn to you now. Adnan's really framed this study nicely, but can you help us from your perspective, put this study in perspective with others that have been published in this space? Dr. Dharam Kumbhani: Yeah, thanks, Greg. And I want to congratulate Adnan and his group for providing the field with another really well conducted study in a very important field. The center has done some very, very landmark trials, and I think this is another one of those. It sort of helps us understand potentially the best treatment mechanism or protocol for patients undergoing primary PCI for STEMI in this case. As you nicely outlined sort of the background for this, the only other trial that I'm aware of in this space is directly comparing pasugrel and ticagrelor head to head was the Prague 18 trial, which was smaller. I think it was about under 1100 patients. So even the STEMI cohort here was larger than that trial. But that trial ended up being terribly underpowered and unfortunately, also discontinued prematurely. So there wasn't really any significant difference that was noted in that trial and there was also a high crossover to clopidogrel in that other trials. Dr. Dharam Kumbhani: So I think that trial, in fact, we had published a trial in circulation as well. And I think this study sort of helps to advance the field a little bit by providing a head to head comparison between the two drugs. If I may extend some of the discussion points that were brought up earlier, I think, again, there is a couple of things that jumped out to me. One is, as you mentioned, the semi cohort is very interesting and very important. The p-value for interaction between the STEMI and the non-STEMI population was not significant for the primary end point. So that is certainly important when considering these results. Dr. Dharam Kumbhani: And the second thing is the differences that were noted in the rates of reinfarction, both spontaneous as well as PCI related. And although that is very interesting, we certainly have to keep that first point in mind when considering that. I think it becomes more hypothesis generating that MI rates ended up being higher with ticagrelor compared with prasugrel, and then sort of trying to tease that out in terms of, was that just a play of chance? Do we end up seeing that, is there a real biological reason for that? All of the trials was extremely well done. There were about 29 patients that did not have one-year follow-up and there were about 67 or so MI events. I think it's very interesting, and I think for at least for me, when I review this trial, I think it brings up some very interesting hypotheses that I think we would need to test further. Those anyway, my sort of high-level thoughts on this excellent trial. Dr. Greg Hundley: Very good. Well, I'd like to ask you just in 20 seconds, each of you, what's the next study that needs to be performed in this field? Adnan, start with you. Dr. Adnan Kastrati: I don't expect trials doing the same thing that we have done in ISAR-X5. We are planning now that ISAR-X6 trial. They are finalizing the protocol, and it will be a large trial of 9,000 patients with acute coronary syndromes in which will test the need for aspirin after discharge. That means all the spaces will be with the potent P2I12 inhibitors. And one group, it will be a placebo controlled trial. One group will have aspirin after discharge, the other placebo. And this is now, for us, the most important thing in this area. Dr. Adnan Kastrati: If I have the chance to respond to Dharam about the mechanistic insights of this effect, I would say that we have shown aggressive cardiology, our data about platelet function. It is the biggest platelet function studies in this area, 600 patients. We have tested in patients after PCI. We tested ADP in used aggregation after ticagrelor and prasugrel. And prasugrel was associated with a 30% reduction in platelet aggregation in these patients. And I think that this offers the mechanistic basis also for our results. And the results will be published shortly. Dr. Greg Hundley: Very nice, and Dharam. Dr. Dharam: Thank you for that response, Adnan. And Greg, to your question, I agree. I think it would be hard, although the field would really benefit from having a head to head comparison between these two drugs again in a larger study. I do think a lot of the interest and excitement in the ACS field is on de-escalation strategies as the outline. And so I suppose that that's sort of where we'll see a lot more in terms of clinical trials. Dr. Greg Hundley: Very good. Well listeners, this has been a wonderful discussion and we appreciate the input from the primary author, Dr. Adnan Kastrati, from the Deutsches Heart Center in Munich and our own associate editor, Dr. Dharam Kumbhani from UT Southwestern. Really reviewing prasugrel versus ticagrelor for primary PCI in patients with STEMI only, and showing really no difference in their primary endpoint of death, myocardial infarction, and stroke, with however an increased risk of reinfection in the patients receiving ticagrelor only. Dr. Greg Hundley: So on behalf of Carolyn and myself, we wish you a great week and look forward to catching you next week On the Run. This program is copyright the American Heart Association, 2020.  

Does Keto Cause Anti Aging?https://rockthatketo.com/?p=2441&preview=true (https://rockthatketo.com/does-keto-cause-anti-aging/) Well, everyone is different, but in general, yes.  The keto diet can create an environment that causes the body to create anti aging chemicals. Younger and skinny?  Wow, great combination.  According to a recent study, there is a natural body chemical called B-hydroxybutyrate. It protects your cells from genetic damage and internal stress.  This happens because it blocks an enzyme.  This enzyme prevents certain good genes from becoming active.  We want these good genes to become active. When these helpful genes become active, they protect the cells from aging.  Yes, I’m simplifying it a lot, but really that’s what you need to know.  Plus the fact that going keto may help prevent a bunch of diseases, including heart and brain problems, like dementia. It’s a Serious StudyThe author of the study,  Dr Katerina Akassoglou works at the Gladstone Institute for Virology and Immunology in San Francisco.    In the study was the question: “Does Keto Cause Anti Aging?” She said: 'The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injury.’ '[These] diseases afflict millions and there are few treatment options.'  I’m not a doctor and I don’t make claims. These are from the Doctor who did the study. We know from lots of research, that when we lower our carbs, and only include ‘healthy’ carbs, our body goes through a big shift in how it burns and stores fat. That process forces the body to secrete B-hydroxybutyrate. Then good things start happening, in addition to losing weight.  There’s Another Way To Activate ItFasting also releases this same chemical, which researchers have known for years.  As you may know, intermittent fasting is one of the things we recommend a lot. I have it built into my daily routine. I don’t eat until lunch time every day. So I have a built-in fast from dinner the night before until lunch, which I usually eat between noon and 1pm. It’s simple, helps me feel better, and keeps the weight steady. It is also anti aging.  Does keto cause anti aging? Apparently yes.  If the keto diet is helping prevent degenerative diseases, it is helping people live happier. Living a long time but being diseased and miserable is not a great bargain. Living long and healthy? That’s a deal I’m interested in. If you like these tips and would like to get more tips, endless recipes, and lots of inspiration, then come to our free website and sign up for our mailing list.https://rockthatketo.com/ ( https://RockThatKeto.com) .  Act! Don’t React! Have a Happy, Healthy Day Livtar

My guest this week is immunologist Dr. Alex Marson. Alex talks about his recent work on SARS-CoV-2, his efforts to translate CRISPR technology to treat patients, and his long-standing collaboration with the Dr. Jennifer Doudna, recipient of the 2020 Nobel Prize in Chemistry. We also discuss how he’s managed to accumulate so many titles at such an early stage in his career: Scientific Director for Biomedicine at the Innovative Genomics Institute and Founding Director of the Gladstone Institute for Genomic Immunology.

There are a lot of people who believe that our world is ruled by a dark, disguised, alien presence.  Are things as they appear to be?  Or is it all just a front to keep the human population feeling like it's business as usual... https://www.theatlantic.com/national/archive/2013/10/how-spot-reptilians-runing-us-government/354496/ PHILIP BUMP OCTOBER 31, 2013 Conspiracy craze: why 12 million Americans believe alien lizards rule us by Olga Oksman Thurs. April 7, 2016; www.TheGuardian.com The World's Population By Eye Color By Victoria Simpson, October 6 2020 in Society https://www.worldatlas.com/articles/which-eye-color-is-the-most-common-in-the-world.html https://www.alienhub.com/threads/no-youre-not-a-reptilian.42684/ Redhead Day: 9 fun facts about red hair: Amanda Kesting 11/5/16 https://www.usatoday.com/story/news/nation-now/2016/11/05/redhead-day-9-fun-facts-red-hair/93341504/ How ESP Works BY TOM HARRIS https://science.howstuffworks.com/science-vs-myth/extrasensory-perceptions/esp.htm Cervical Rib: Thoracic Outlet Syndrome Authored by Dr Colin Tidy, Reviewed by Dr Laurence Knott | 10 Nov 2016 https://patient.info/bones-joints-muscles/cervical-rib-thoracic-outlet-syndrome#:~:text=a%20cervical%20rib%3F-,About%201%20in%20200%20people%20are%20born%20with%20an%20extra,cervical%20vertebra%20in%20your%20neck. https://www.quora.com/Why-do-I-feel-like-Im-not-human Aliens And 'Reptilians': US Viral Video Doctor's Odd Beliefs; Issam AHMED July 28, 2020 https://www.barrons.com/news/aliens-and-reptilians-us-viral-video-doctor-s-odd-beliefs-01595969705 THE PSYCHOLOGY OF EXTRAORDINARY BELIEFS: Behind the Belief: Lizard People February 12, 2019 https://u.osu.edu/vanzandt/2019/02/12/behind-the-belief-lizard-people/comment-page-1/ The Royal Family are bloodsucking alien lizards - David Icke By The Newsroom Monday, 30th January 2006 https://www.scotsman.com/news/uk-news/royal-family-are-bloodsucking-alien-lizards-david-icke-2478194 We Are “Sheeple,” and Our Overlords Lizard Aliens. (Who Came From Inside the Earth). NOV. 15, 2013 By Hua Hsu https://nymag.com/news/features/conspiracy-theories/david-icke-sheeple/ Is Queen Elizabeth an extraterrestrial reptile? Some of the most bizarre royal conspiracy theories Bashiera Parker https://www.news24.com/channel/gossip/royal-news/is-queen-elizabeth-an-extraterrestrial-reptile-some-of-the-most-bizarre-royal-conspiracy-theories-20200615 32 Royal Conspiracy Theories That Are Absolutely Bonkers From robot Meghan Markle to a Beyoncé feud, these theories will give you a good laugh. BY AMY MACKELDEN JULy 29 2019 https://www.harpersbazaar.com/celebrity/latest/g21551924/royal-conspiracy-theories/ A band of reptile humanoids may be responsible for history’s greatest tragedies, Reptilian Elite: The beasts among us by Alyssa Anderson, October 24, 2017 https://www.spectatornews.com/opinion/2017/10/a-band-of-reptile-humanoids-may-be-responsible-for-historys-greatest-tragedies/ Fringe Conspiracy Theorists Think Trump Is an Immortal Alien, Got COVID as Cover to Shapeshift (October 5, 2020) MJ Banias https://www.vice.com/en/article/akzxae/fringe-conspiracy-theorists-think-trump-is-an-immortal-alien-got-covid-as-cover-to-shapeshift What to Know About the Bilderberg Group's Secret Annual Meeting (JUNE 9, 2016) BY JOSH SANBURN https://time.com/4362872/bilderberg-group-meetings-2016-conspiracy-theories/ https://reptilian-resistance-movement.webs.com/aboutus.htm Naked lizard proves hair, scales and feathers descend from single reptilian ancestor, study says (June 24, 2016) By Leigh Anne Tiffany https://www.pbs.org/newshour/science/naked-lizard-proves-hair-scales-and-feathers-descend-from-single-reptilian-ancestor-study-says#:~:text=Scientists%20have%20uncovered%20the%20link,approximately%20320%20million%20years%20ago. First Genetic Link Between Reptile And Human Heart Evolution Found(September 3, 2009) Gladstone Institutes https://www.sciencedaily.com/releases/2009/09/090902133629.htm

Last July I had the pleasure of talking with Dr. Melanie Ott, the Director of the Gladstone Institute of Virology in San Francisco. While I would have been thrilled to talk to her under any circumstance, the ongoing SARS-CoV-2 pandemic has made one-on-one time with a virologist more valuable than ever. In addition to catching up on the latest news about COVID-19, we discussed her long-standing interest in HIV and the surprising similarities between unrelated viruses.

Dr. Benoit Bruneau is the Director of the Gladstone Institute of Cardiovascular Disease. His lab uses mouse models and human iPSCs to investigate the transcription factor networks that regulate sets of genes critical for heart development.

Deepak Srivastava is president of Gladstone Institutes. He is also the Younger Family Professor and a senior investigator at the Gladstone Institute of Cardiovascular Disease and director of the Roddenberry Stem Cell Center. At UC San Francisco (UCSF), Srivastava is a professor in the departments of pediatrics and biochemistry and biophysics. Today, he discusses novel approaches to COVID-19 diagnostic testing, treatments, and prevention. Dr. Srivastava dives right into the three key components of the COVID-19 pandemic that will affect how we move forward. He maintains that chief among those components - testing, treatment, and prevention via vaccine - is the improvement needed to diagnostic testing. By moving from the current method of lab testing, which is expensive and tests by amplifying viral genomes, to a test done in real time, we can begin reopening businesses and resuming a sense of normalcy. One possibility he suggests is the work being done by a virologist at the Gladstone Institute using CRISPR technology and enabling a smartphone camera to operate as a microscope, eliminating the need to amplify genomes and send every test to a lab for results. Go to NoLabels.org to learn more about how we are bringing together a bipartisan group of public and private leaders working to stop the virus, save lives and get Americans back to work.

Robert Wicks is the vice president of philanthropy and CEO of the Gladstone Institute. Prior to joining Gladstone, he was the director of West Coast Advancement at Dartmouth College based in the Bay Area. From 2006 to 2014, he worked in a series of frontline fundraising roles for Stanford's Office of Development and the Graduate School of Business, specializing in the venture capital and entrepreneurial communities.  Robert is a board member for YCore and has served as an advisor to the social entrepreneurs at the Draper Richards Kaplan Foundation, the Hasso Plattner Institute of Design at Stanford, and Care Message. Robert has a BA in English from Binghamton University and was a Ph.D. candidate in the English Department at UC Berkeley. In this episode… Are you always thinking of ways to improve your fundraising efforts? According to Robert Wicks, one of the ways through which you can improve donor communications and improve your fundraising strategies is by employing design thinking, a process that helps in creating concepts and ideas that are not only better but also more efficient and accurate. Design thinking allows fundraisers to structure a donor-centered conversation and helps build the right momentum for the donor request. According to Robert, there are seven types of conversations that fundraisers need to get better at in order to become successful in their fundraising career. Join Penny Cowden in this episode of Philanthropy212 as she discusses with Robert Wicks of Gladstone Institutes Foundation what design thinking is and the impact of structuring donor-centered conversations. They will also be talking about tribal wisdom and its role in the fundraising community and find out the different types of conversations that fundraisers need to be good at in order to improve their fundraising skills. Stay tuned. 

Dr. Deepak Srivastava is the President of the Gladstone Institutes and the International Society for Stem Cell Research, and the co-founder of Tenaya Therapeutics. His lab investigates the gene networks that guide cardiogenesis by developing models of heart disease using patient-derived iPSCs and CRISPR technology.

Bay Area biotech companies are using their resources to fight the COVID-19 pandemic. Dr. Warner Green is a senior biologist and clinician with Gladstone Institutes in San Francisco. He and his colleagues are using techniques developed in AIDS research to understand the life cycle of the coronavirus that causes COVID-19 and how existing drugs that have already been tested could be used to treat patients.

Dr. Todd McDevitt is a Senior Investigator at the Gladstone Institutes and a Program Director and Professor at UCSF. His research focuses on engineering 3D, multicellular systems that can be used to study principles of stem cell and developmental biology.

Over the last 10 years, people have been looking for HIV’s hiding place. Mainly what they did was they tried to find the virus in a certain organ and in a certain cell, and quantify that. But, as the virus evolves before you start the antiretroviral therapy, the organs in the body are infected with a slightly different virus, so a new approach had to be looked at, in order to find the viral reservoir.In this episode, Professor Vandekerckhove shares his laboratory’s latest discovery – the location of the viral reservoir – and breaks it down for us to understand the impact this has on finding a cure for HIV and ending the epidemic.Prof. Dr. Linos Vandekerckhove is the principal investigator at the HIV Cure Research Center in Ghent, Belgium, which he founded in 2009. He graduated from the Medical School KULeuven in 1998 and obtained his Ph. D. in 2006 from the Rega Institute, also in Leuven. In 2001 he worked for a year at the Pretoria Academic Hospital in South Africa, in the service of Internal Medicine.In 2009 he started his own laboratory and a year later he spent 5 months in San Francisco to familiarize himself with research on a cure. He combined his infectious disease specialist education program with a Ph. D in Professor Debyser’s laboratory for Molecular Virology. With this combination, he bridges the gap between Clinical Infectious Disease at the AIDS clinic and basic Molecular Virology research.In 2010 he worked as an invited researcher at the Gladstone Institute in Eric Verdin and Warner lab. Since then, he has been working as an assistant professor in Internal Medicine at the University of Ghent, Belgium. Today, his laboratory is a team leader for HIV reservoir research.Listen to Episode 12 of Positively Alive, to learn about the latest discovery in this field - the location of the viral reservoir of the HIV virus – and what that means for people living with HIV.Questions I ask:Could you please elaborate a little bit on why the HIV Cure Research Center was established, and what exactly do you do at the research center? (03:59)How easy is it to find patients for your studies? (08:30)How do you manage the risk that is involved with doing those research programs? (09:17)You have also mentioned that if someone is on treatment and suddenly stops that treatment, the virus will have a rebound that is faster than compared to before. At what exact rate does it rebound, and does it also mean that the virus has become stronger? (13:51)How hopeful are you, really, that we are close to a cure for HIV? (18:52)What are the specific needs of the HIV Cure and Research Center? (21:26)What would you say to young researchers who start a career in this specific area? (25:30)In this episode you will learn:The importance of international collaboration in actually finding a solution to the epidemic. (06:20)Where the HIV viral reservoir is located inside the body. (10:23)The impact on the HIV positive individuals that this new discovery has, in terms of medication and costs. (17:10)The significance of U=U within the context of the HIV Cure and Research Center studies. (22:59)Linos’s message for people living with HIV today. (26:42)Positively Alive Resources:WebsitePositively Alive Youtube ChannelInstagramFacebook GroupFacebook PageTwitterDonate See acast.com/privacy for privacy and opt-out information.

This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights five featured articles from recent issues of Circulation Research and talks with Matthew Stratton, Rushita Bagchi, and Tim McKinsey about their article on Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation. Article highlights: Vincentz, et al. HAND1 Enhancer Variation Impacts Heart Conduction   Zhuang, et al. EC-Klf2-Foxp1-Nlrp3 Regulates Atherogenesis   Quintanilla, et al. Robust Targets for Persistent AF Ablation   Lambert et al. Characterization of Kcnk3-Mutated Rats   Myagmar et al. Gq Mediates Cardioprotection Transcript Cindy St. H:       Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you highlights from recent articles published in the August 30th and September 13th issues of Circulation Research. We'll also have an in-depth conversation with Drs. Matthew Stratton, Rushita Bagchi, and Tim McKinsey, who are the lead authors of one of the exciting discoveries presented in the September 13th issue. Cindy St. H:         The first article I want to share with you is titled, "Variation in a Left Ventricle–Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function." The first author is Joshua Vincentz and the corresponding author is Anthony Firulli, and this work was conducted in the Departments of Pediatrics, Anatomy, and Medical and Molecular Genetics at Indiana Medical School in Indianapolis, Indiana. Cindy St. H:         The heart's ventricular conduction system, or VCS, is composed of specialized muscle cells that propagate electrical signals through the working myocardium of the ventricles to coordinate the rhythmic contractions of the heart chambers. Disorders of the VCS can lead to certain types of arrhythmia. Genome-wide association studies have identified a number of single nucleotide polymorphisms, or SNPs, that appear to increase the risk of VCS-mediated arrhythmias. Two such SNPs are located in the upstream region of a gene encoding for Hand1. And Hand1 is a transcription factor that is involved in left ventricle development. Conditional cardiac Hand1 ablation during embryogenesis leads to ventricular septal defects and hyperplastic arterial ventricular valves, and a reduction in Hand1 expression could lead to morphological, and therefore functional defects. Vincentz and colleagues hypothesized that these SNPs might reside in an enhancer element, and that's a region of DNA and a promoter that allows for the increased expression of a gene. The region containing the SNPs is highly conserved from mammals to reptiles and includes two sequences that allow for the binding of GATA transcription factors. And GATA transcription factors are well known to drive cardiac development. So this team used CRISPR-Cas9 technology to show that the deletion of the enhancer impaired normal VCS morphology and therefore function. And they did this in a mouse model and in the in vitro electromobility shift assay (which frankly was one of my favorite love-to-hate experiments of my PhD). So this group did their own electromobility shift essay and showed that GATA-4 binds to these enhancer sites. And together, these results support a role for Hand1 in the formation and function of the VCS and offer insights to possible arrhythmia etiologies. And what I really love about this paper is that they could actually go from a SNP in a GWAS to a functional role of a protein, which is great. A lot of times with GWAS studies, you have no clue what the heck is going on. So this was a beautiful study where they actually could link a single nucleotide polymorphism to differential expression of a gene. Cindy St. H:         The next article I'd like to highlight is titled, "Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation." The first authors are Tao Zhuang and Jie Liu, and the corresponding authors (there's three of them) are Zhongmin Liu, Muredach Reilly, and Yuzhen Zhang. The Liu and Zhang teams are from the Key Laboratory of Arrhythmias of the Ministry of Education of China, and the Research Center for Translational Medicine at Shanghai East Hospital, which is part of Tongji University School of Medicine in Shanghai. And the Reilly team is from the Cardiology Division in the Department of Medicine and the Irving Institute for Clinical and Translational Research at Columbia University in New York, New York. And I have to say my good friend Rob Bauer is also a coauthor on this article. So Rob, I hope you're listening. Cindy St. H:         Chronic inflammation contributes to atherosclerotic disease and is a major pathological mechanism contributing to the dysfunction of the vascular endothelium. So leukocytes, which are inflammatory cells that float around in your blood, leukocytes can adhere to the endothelial layer, and then they can migrate through the endothelial wall into the wall of the vasculature. And it's this activity, along with the uptake of oxidized LDL and the formation of a little fatty streak, that is the start of atherosclerosis. And now Zhuang and colleagues have identified that the transcription factor Foxp1 is a potential regulator of vascular endothelial health. So first they showed that while healthy arteries express Foxp1 robustly, atherosclerotic endothelium from both mice and humans exhibits reduced expression of this transcription factor. The team then generated atheroprone mice that either lacked Foxp1 or overexpressed Foxp1 specifically in the endothelium. The mice lacking Foxp1 were shown to have exacerbated athero with much larger plaque sizes and increased macrophage infiltration into the vessels, while overexpression of Foxp1 had largely the opposite effect. It actually curtailed progression of atherosclerotic disease. The team went on to examine the atherosclerosis-suppressing mechanism of Foxp1, showing that the factor suppressed expression of the inflammasome components in the endothelial cells. Cindy St. H:         So all together, these results highlight that Foxp1-mediated regulation of the inflammasome is a potential targetable pathway for atherosclerotic treatments, and having a new targetable pathway is important, as the CANTOS trial, which provides proof of concept of the inflammation hypothesis of atherosclerosis in humans, showed robust effects in only a small subset of the population tested. Thus, there is a need to identify other means, a plan B if you will, by which we can control the inflammation that contributes to atherosclerosis. Cindy St. H:         The next paper I want to highlight is titled, "Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation." The first author is Jorge Quintanilla, who is also a corresponding author alongside David Filgueiras-Rama, and they are from the National Center for Cardiovascular Research and the Center for Biomedical Research in Cardiovascular Diseases Network in Madrid, Spain. Uncoordinated contractions of the atria to the ventricles of the heart is called atrial fibrillation, or AFib, and AFib causes symptoms such as heart palpitations, dizziness, and taken to the extreme, AFib can actually cause death. To correct such rhythm problems, doctors can ablate certain regions of the heart suspected to be driving this misfiring. In an ablation procedure, a catheter is inserted through the blood vessels and into the heart. An electrophysiologist then identifies the locations of the heart that are sending abnormal electrical impulses, and with either delivery of tiny pulses of painless, low-level energy or using a catheter that has a cold tip to freeze the misfiring areas, the electrophysiologist can ablate and hopefully stop  AFib. The problem is that this approach often fails, and AFib still occurs or can reoccur after a length of time. So Quintanilla and colleagues wanted to develop a more personalized medicine approach to treating AFib. So to do this, they wanted to make it something simple, something affordable, and something that hospitals currently have access to. So they used the standard electroanatomical mapping system to track the amplitude and also the frequency modulations of the electrical signals from the hearts with AFib. And they found that regions with high and stable instantaneous frequency signals were the drivers of fibrillation in the hearts. When these regions were ablated in pigs with persistent AFib, the misfiring stopped in almost all cases and was sustained. The team went on to test the system in three patients with Afib, and two of the three remained arrhythmia-free without drugs for at least 16 months. So with further development and testing, this frequency mapping could potentially replace systems that are currently in use, and more importantly, this could provide a more accurate and patient-tailored way to find and ablate the drivers of AFib. Cindy St. H:       The next paper I want to highlight is titled, "Characterization of Kcnk3-Mutated Rat, a Novel Model of Pulmonary Hypertension." Oh, now that was a nice title. That was nice and short. The first author is Mélanie Lambert, and the corresponding author is Fabrice Antigny, and they are from the INSERM Hôpital Marie Lannelongue in Le Plessis Robinson, France. Cindy St. H:       Pulmonary hypertension is a rare but life-threatening condition where the adverse remodeling of the pulmonary arteries causes an increase in the blood pressure that's needed to push the blood through the lungs, and this high blood pressure causes the heart to work harder, and it leads ultimately to right ventricular hypertrophy and heart failure. So genome-wide association studies have identified a number of mutations that have been linked to pulmonary hypertension and these include several loss-of-function mutations in the gene encoding for a potassium channel, and that's a protein that can release potassium from a cell to the extracellular environment. And the particular one that has been found to be mutated in pulmonary hypertension patients is Kcnk3. And this channel regulates the resting membrane potential of pulmonary artery smooth muscle cells. To date, it is not known how the loss of Kcnk3 contributes to pulmonary hypertension. To start to unravel this mystery, Lambert and colleagues created a full-body knockout of Kcnk3 in rats, and they used rats because that's a much more robust model for studying pulmonary hypertension than some of the murine models available. These knockout animals exhibited an increased pulmonary artery pressure. They also had faster heart rates and they were more susceptible than their wild-type counterparts to both pharmacological or hypoxia-induced pulmonary hypertension. These Kcnk3 knockout rats also had evidence of remodeled pulmonary vasculature, and this vasculature showed signs of endothelial dysfunction, altered vaso transcription, and altered neomuscularization. In in vitro studies, they used pulmonary artery smooth muscle cells that they isolated from these knockout rats, and these cells showed increased activation of proliferation markers, which is another signature of pulmonary hypertension. And this was also mirrored in human pulmonary artery smooth muscle cells that were treated with a Kcnk3 inhibitor. So together, this work starts to uncover the role of Kcnk3 in pulmonary hypertension pathogenesis. And it also provides the field with a novel model system from which people can learn more about the role of membrane potential of pulmonary artery smooth muscle cells in pulmonary hypertension. Cindy St. H:       The last paper I want to highlight before our interview is titled, "Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist." The first author is Bat-Erdene Myagmar, and the corresponding author is Paul Simpson from the VA Medical Center in San Francisco, California. So like their name says, G-protein coupled receptors interact with G-protein subunits to propagate the signal when a ligand binds. The protein G alpha q has long been considered a key mediator of cardiac hypertrophy. And that's because in mice, when this Gq protein was overexpressed, it induced hypertrophy, myocardial apoptosis, and contractile failure. However, this sub unit Gq can interact with a multitude of G-protein coupled receptors that themselves bind a variety of ligands. So which receptor or which signaling pathway specifically is responsible for the hypertrophic phenotype? Recent studies by others had shown that stimulation of the alpha-1A adrenergic receptor prevents cardiotoxicity and heart failure. So Myagmar and colleagues asked whether this cardio-protective alpha-1A stimulation is dependent on the alpha q subunit. So using mice with a mutant version of alpha-1A that allows the binding of the ligand but does not couple with the Gq subunit, the team found that alpha-1A induced cardioprotection was absent. The mutant animals were more likely to die than their wild-type counterparts when hypertrophy was induced pharmacologically or surgically. And furthermore, in the mutant myocytes themselves, the group observed that alpha-1A induced ERK signaling, which is essential for the receptors cardioprotective activity, was impaired. So together these results showed that alpha-1A-induced cardioprotection is dependent on alpha q, and actually it showed that alpha q signaling is not always maladaptive. Cindy St. H:       Now we're going to move to our interview with Drs. Matthew Stratton, Rushita Bagchi and Tim McKinsey and we're going to talk about their great paper titled "Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation." Cindy St. H:       Okay, so now we're going to have our interview with Drs. Stratton, Bagchi, and McKinsey on their paper titled, "Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation." So welcome, everyone. Dr Tim M:          Thank you. Dr Rushita B:    Thank you. Dr Matt S:          Thank you. Cindy St. H:       I was wondering if you could just all maybe go around and introduce yourselves. Dr Tim M:          Sure. I'm Tim McKinsey. I'm a professor in the Division of Cardiology at the University of Colorado Anschutz Medical Campus. I also direct a newly formed fibrosis center on campus. It's called the CFReT, the Consortium for Fibrosis Research and Translation, and our goal is to understand new mechanisms that regulate fibrosis and develop new therapies to treat scarring, or fibrosis, in organs. Dr Rushita B:    I'm Rushita Bagchi. I'm currently a postdoctoral fellow in Dr McKinsey's lab. I grew up in India, and that's where I did my undergrad and master's degrees. Then I moved to Canada to do my PhD focusing on transcriptional regulation of cardiac fibrosis under the supervision of Dr Michael Czubryt. After that, I transitioned to Dr McKinsey's lab here in Denver to enhance or add to my expertise of transcription by studying epigenetics, and especially trying to find the underlying mechanisms that cause cardiovascular disease. The nice thing about this position for me has been that I have been able to constantly build up on my experience studying tissue fibrosis, but at the same time, Tim has been very generous and has let me develop projects of my own as well. Cindy St. H:       You're lucky. That's awesome. Thank you for joining us. And Dr Stratton. Dr Matt S:          I'm Matt Stratton. I'm an assistant professor in the Department of Physiology and Cell Biology at Ohio State University. I did my graduate training at Colorado State University in neurodevelopment and neuroendocrinology and then moved to Tim's lab for a postdoc and assumed my current position this past December. Cindy St. H:       Wow. How's it going? Dr Matt S:          It's going well. Starting a lab is a lot of fun and a lot of stuff going on. Cindy St. H:       Yeah, I'm four years in now and at the same time you feel brand new and excited and then, oh my God, what am I doing? So that's great. Well thank you all for joining me. So I really like this paper, mostly because I'm also a vascular biologist. I kind of focus more on the heart valves, but I have a real interest in cell phenotype transitioning and cell shifting, and so when you started to talk about chromatin remodeling and bromodomain protein, I was really interested and wanted to hear more. So maybe we can start by telling everyone what is the clinical need that your paper at base is trying to address? Dr Tim M:          Well before we get into that, could I start by saying that we're honored to have our work published in Circulation Research. We're really grateful for that. I also want to point out that this is the result of a very detailed collaborative effort involving at least six other labs, including the labs of Charles Lan at Baylor College of Medicine, Jun Qi at the Dana-Farber Cancer Institute, Kunhua Song and Maggie Lam here in Colorado, as well as Sap Haldar and Deepak Srivastava at the Gladstone Institutes in San Francisco. Without this collaborative effort, none of this would have been possible. Cindy St. H:       That's great to hear and I'm really happy you mentioned that. Team science is so important, and I feel like we almost can't get these big, groundbreaking papers unless we really work as a good team, so thank you for highlighting that. Dr Tim M:          So we're really interested in fibrosis, which is a hallmark of heart failure. Fibrosis can actually be a good thing for the heart. If you have a myocardial infarction, you need a strong scar to form to prevent the ventricle from rupturing. But in response to chronic stress like hypertension and other things, you can get this longstanding fibrosis that results in cardiac dysfunction. That's because fibrosis is essentially a scarring process and one of the things that that does is to create a stiff in the left ventricle that can't relax effectively. Unfortunately, despite the well-known roles of fibrosis in cardiac disease, there are no targeted anti-fibrotic therapies for the heart, and that's really our focus in the lab. We've had a long-standing interest in epigenetic regulation of heart failure and cardiac fibrosis, and we've known for some time that inhibitors have a family of epigenetic reader proteins called the bromodomain and extraterminal proteins, the BET proteins. Inhibitors of those BET proteins can block cardiac fibrosis in rodent models and improve cardiac function. What we knew going into this work is that systemic delivery of those compounds was efficacious. But as you know, the heart is made up of many different cell types. So we really wanted to understand if the efficacy of these compounds was related to effects in resident cardiac fibroblasts. Cindy St. H:       Excellent. So what is the role of a cardiac fibroblast in a healthy cell, and where does that go awry? Dr Matt S:            So in a undiseased heart, fibroblasts are necessary to provide structure, right? They lay down the extracellular matrix that really holds the heart together. Without them, you would not have a good pump function. Where they go awry, I mean, that's one of the things that we're trying to study, right? They become proliferative, they become contractile, and they secrete, or we call them super-secretors, of extracellular matrix. So TGF-beta is really a known signaling molecule that kicks the fibroblasts into this activated or myofibroblast state. We use that in the paper as a agonist for our cultured cells. Cindy St. H:         Great, thank you. So what was the hypothesis you were testing in this paper? Dr Matt S:            So what we wanted to know, if BRD4 and BET proteins are important for this activation of cardiac fibroblasts? So going from a quiescent fibroblast to a proliferative and super-secretor of extracellular matrix fibroblast in the heart. And those experiments hit right away. I mean, we did those experiments, and it was quite dramatic that if you use JQ1 to inhibit these BET proteins, you completely blocked this myofibroblast differentiation. We went in and did some siRNA and shRNA work to show that really BRD4 appears to be the main culprit of the BET protein families. Cindy St. H:         Rushita, could you tell us a little bit about what a bromodomain protein is and what maybe specifically BRD4 is in relation to the other bromodomain proteins? Dr Rushita B:      Sure. So when we talk about the chromatin, there are various players in there that are known as, in general, chromatin modifiers. So you have enzymes that add acetylation mark on lysine residues on histone tails, which is basically DNA is wound around these histones and those histones have lysine tails, but you have the big acetyl group sitting. Now when you have this acetyl group sitting, this makes it more accessible for the transcriptional machinery and allowing gene transcription to happen. Those enzymes are known as histone acetyltransferase, the ones that add the acetyl mark there. The ones that take it away, which is what our lab has been studying for a long time, and Tim is a known world expert in the field, those are known as histone deacetylases, or HDACs, which basically remove those acetyl marks and compact the chromatin, thereby suppressing gene expression. This BET proteins or bromodomains are transcriptional coactivators. So this bromodomain is actually in charge or takes up the duty of identifying these acetyl marks on the lysine residues and therefore, tells the transcription machinery to come in and allow gene transcription to happen. There are a few BET proteins. Of them, BRD4 has been studied extensively in cancer as well as in the heart. But as Tim mentioned, the role of BRD4 has been studied vastly in the heart in terms of the cardiac myocytes, but not so much in the non-myocyte population, which is where our work stands out really well and starts highlighting the role of this specific chromatin modifier protein in activation or control of profibrotic gene expression. Cindy St. H:         Yeah. So correct me if I'm wrong, but my understanding is, you're going to need a little bit of the cardiac fibroblasts remodeling in the early phase. But where it is really detrimental is when that overcompensates and overproliferates and throws down too much matrix and then is bad. So do you see your study as a way to kind of target that window of where a potential treatment might be applicable? Dr Tim M:            Yeah, we think that BRD4 is a nodal regulator of cardiac fibrosis and therefore, an excellent therapeutic target. The challenge will be developing selective BRD4 inhibitors that are safe, as well as effective. We know that BRD4 is not only expressed in cardiac fibroblasts-it's all over the body. But we think our work provides an entry point to the development of highly selective BRD4 inhibitors for fibrotic indications, including heart failure. Cindy St. H:         So that's one of the things I was wondering, how specific your drug is to BRD4 versus the other ones, but also you mentioned the myofibroblast versus the immune cells infiltrating the heart. Do we know what BRD4 is doing in those cells in this system? Dr Tim M:            BRD4 is definitely pro-inflammatory, and BET protein inhibitors like JQ1 are anti-inflammatory, that's for sure. Interestingly, there's a BET family inhibitor called Apabetalone, RVX-208, that's in Phase III clinical testing for people with atherosclerosis. So if that's successful, it will provide proof of concept that you can target this family of epigenetic readers to treat cardiovascular disease. I also wanted to point out that JQ1 was initially discovered by Jay Bradner's lab, in particular Jun Qi, who is a coauthor and collaborator on this paper. Cindy St. H:         Oh, very nice. Okay, good conflict of interest too, I guess. So maybe you guys can talk a little bit about how you managed to get this huge team of scientists together efficiently, and what were any hang-ups? Matt is laughing a bit, but you two are the lead authors, Matthew and Rushita. How did you two kind of lead the way on this and divvy up this huge project? Dr Matt S:            So it is definitely a project management-style approach I think you have to take. I mean, there's a lot of communication, really a lot of communication with bioinformatics, analysts, and getting the right sequencing done, and that was fun, but it took a lot of effort. And once you get this big data, how do you present it in an intelligible story and how do you pick things out that may lead to new discoveries, right? So we highlight Sertad4 in here as a gene that's very much BRD4-dependent. And I think this is a proof of concept for using this genomics, and particularly BRD4, as kind of a molecular string to pull on to unwind this puzzle. So that was a lot of fun. And you know, Rushita was super awesome in helping with this project. Dr Rushita B:      Yeah, I think having stared at cardiac fibroblasts for six years during my PhD definitely gave me the confidence that I could step up to the plate and deliver what was necessary. And like Matt said, there was a lot of omics-based stuff that we did in the paper. And that is actually one of the key highlights, because we see papers or manuscripts that are published that have RNA-Seq, ChIP-Seq and proteomics, but I believe the strength in our article is the combination of all three. So we were actually able to do overlapping ChIP-Seq and RNA-Seq experiments, and then there was proteomics involved. So we are looking at it at the genomic transcriptome and protium-wide changes that are happening all together, put in one manuscript. And the beauty of this work is it has now created data sets that people can mine and get more information out of. And this is something that will definitely continue to drive our future studies in the lab as well. Cindy St. H:         Can you maybe expand on that? Could you maybe describe briefly for the audience what ChIP-Seq is and what RNA-Seq is, and really the power that is created when you can couple those techniques with the same samples? Dr Matt S:            Sure. So BRD4 was the center point of the paper, right? So we did BRD4 ChIP-Seq and RNA Pol II ChIP-Seq in fibroblasts treated with TGF-beta or not. So in ChIP-Seq, you basically immunoprecipitated your target protein, and that brings with it, if it's bound to chromatin, that brings with it the DNA that it's bound to. And then you can sequence the DNA that comes out of your immunoprecipitation and map that to the genome, and you get a very nice picture of where is BRD4 enriched, and where does it go after stimulation like TGF-beta, when the fibroblast becomes a myofibroblast. So you can line all these up and you can pick out what gene changes we think are directly dependent on BRD4. That's something that we like, because we now know that BRD4 is a good target, right, so that kind of pulls it together. Cindy St. H:         Great. Thank you. What else do you want to bring up? Dr Matt S:            I think understanding how signals get translated to changes in gene expression is obviously something that the field is very much interested in. And because BRD4 is basically a step away from RNA polymerase II, it gives you a little bit more specificity in knowing that that's a disease-activated pathway, right? So trying to figure out what directs BRD4 to new locations in the chromatin and cause it to be removed from previous locations in the chromatin is really an interesting area of research. So we did a pathway screen basically using inhibitors, and we use Sertad4 as the readout, right. And we found that a p38 inhibitor was able to block the ability of TGF-beta to induce Sertad4. And we were able then to show that p38 had a role in targeting BRD4 specifically to the Sertad4 locus. Dr Tim M:            I wanted to say, you know, one of the challenges with this project is that fibroblasts are difficult to work with. You would think that they would be easier to work with than a myocyte. But when a fibroblast hits a plastic cell culture dish, it rapidly transforms into an activated cell, because that plastic has a very high tensile strength. So it took a lot of optimization to figure out methods to culture these cells to maintain them in a quiescent state. Cindy St. H:         What did you do? What was that trick? Dr Tim M:            I mean, it involves changing cell density, changing the constituents of the medium, and doing other things. Cindy St. H:         Science magic. Dr Tim M:            Yeah. Dr Rushita B:      And I'll just add to that. The nice thing about being able to contribute to a study like this is also that, like Tim said, fibroblasts, they change phenotype rapidly. You take them out of a biological system, whether it's a heart or any other tissue, you plate them out in cell culture, they start changing. The nice thing about the in vivo study, the RNA-Seq that was done using the in vivo study with JQ1, was that we used a very simple pressure overload model known as the TAC model, which is a very well-established and accepted model worldwide in the field of cardiovascular disease, treating animals with JQ1. So we isolated fibroblasts, but the time from the isolation of cells to the time an RNA was prepared was an hour or two. So we made sure that we minimally exposed them to culture conditions in the lab, so we retained their biology. So what we did on plastic dishes before, although they were plated on plastic, and we had RNA-Seq done on those cells, like Tim said, we did optimize the conditions. And then being able to similarly treat or use the cells that come from an animal directly and both of them contributing to a similar cohort of genes or pathways that we can look at, that has definitely given immense strength to this manuscript. Cindy St. H:         And that's why it's in Circ Research, so it's a beautiful paper. Very well done. So I can't imagine all these hearts that you had to isolate and get single cells of and culture. What kind of days were you pulling? What was the actual boots on the ground of getting this done? How did that work? Dr Tim M:            It wasn't uncommon for me to get emails from Matt and Rushita at very odd hours of the night or early in the morning. Dr Rushita B:      Yeah, it was like we had the animals being sacrificed, hearts taken, and running to the cell culture room to do everything under sterile conditions. Most important thing- I think what worked out really well is we made sure we had all the reagents prepared ahead of time, so that once the heart is out, it's weighed, because we were also looking at hypertrophy because of the TAC model. We weighed the heart and it goes into your BST right away. Cindy St. H:         I try to teach that to my lab. It's like the cooking idea of mise en place. I make them lay out everything in the cell culture hood ahead of time, and it's all in the order and you just boom, boom, boom, boom. Dr Rushita B:      And a lot of our experiments were done later in the evening, so the nice thing was we had access to multiple centrifuges, which is usually a huge plus. And I still remember Matt being on one side, I'd be on the other. And then we had help from members of the lab as well. They were running between the cell culture room and the centrifuge. So it was actually quite fun. It turned out really well. Cindy St. H:         I'm picturing like those old water brigades to put out a fire where like a bucket is just passed. Is that what this was? Dr Rushita B:      That was very similar to the situation you just talked about. Cindy St. H:         That's great. It sounds kind of painful, but also kind of fun. I guess lastly, maybe one of you can end with telling us what are the bigger picture results of this, and what are the next steps in terms of maybe possibly translating this to the clinic? Dr Tim M:            Well as I mentioned, one of the things we're trying to do is to selectively inhibit BRD4. We're also trying to inhibit it only in cardiac fibroblasts with the hope that we'll be able to improve the therapeutic index of BRD4 inhibition. So create a situation where patients can tolerate this anti-fibrotic therapy better than if it was delivered systemically. We're also looking at other regions of BRD4. BRD4 contains the bromodomains, and those are the targets of JQ1, but there are other interesting domains on BRD4 that we're actively pursuing. Cindy St. H:         Thank you. And Matthew, what are you doing in your new lab, or is it just set up right now? Dr Matt S:            Well I have a K Award from the National Institute of Aging. Cindy St. H:         Congratulations. Dr Matt S:            Thank you. To look at BRD4's role in the heart and cardiac aging. And I also have a couple projects based on some of the mining that we've done from these datasets. So hopefully those lead to good publications and follow-on grants. Cindy St. H:         Well, if this is a good start, I'm sure they will. And Rushita, what are your next plans? How long have you been with Tim? Dr Rushita B:      So I've been here with Tim for almost four years now, so I'm pretty much in the final leg of my postdoctoral training. So I'm still continuing to work on tissue fibrosis projects, including the heart. But I have been able to develop a new field of interest and something that Tim has entrusted me to carry on in the lab in the field of cardiometabolic disease, but definitely with an epigenetic focus. So hopefully in a year's time I see myself having an independent academic scientist position. My dream job will be to be at an academic institute where I can lead a research team which focuses on deciphering or trying to even find the most basic molecules that define the underlying mechanisms of tissue fibrosis and cardiometabolic disease. Cindy St. H:         That sounds like a great plan. Very best luck to you. Dr Rushita B:      Thank you. Cindy St. H:         Do you guys want to add anything else? Dr Tim M:            The field of cardiovascular epigenetics is in its infancy and we still have a lot to learn. Cindy St. H:         And I'm sure all of you will do your parts in moving that field forward. So with that, we're going to end our interview with Drs. Stratton, Bagchi, and McKinsey. Thank you all for joining me and thank you to the listeners for listening. Have a great day. Dr Tim M:            Thank you. Dr Rushita B:      Thank you. Dr Matt S:            Thank you. Cindy St. H:         That's it for highlights from the August 30th and September 13th issues of Circulation Research. Thank you for listening. This podcast is produced by Rebecca McTavish, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St Hilaire, and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.

Navigating the world of graduate school or postdoctoral studies can be an immense challenge. Those inherent difficulties are even greater when the student is working and studying in a culture different from the one he or she grew up in. For those who are studying in the United States and originally from abroad, who do they turn to for guidance and mentorship? Where can they go to learn the skills to be leaders in their respective fields and in the world? Dr. Sudha Krishnamurthy has overcome both challenges and enjoys helping and mentoring those who are traversing the roads she has already traveled. She is a clinician-scientist with over seven years of experience doing research in cancer biology. She has expertise and experience in 3D cell culture, fluorescence microscopy, cancer stem cell biology, in-vivo pharmacology, anti-angiogenic agents and animal models. She enjoys working with teams and has strong analytical and problem-solving skills.  Sudha has so far had an incredibly diverse professional career helping graduate students and postdocs by sharing her rich experience doing the same. She is the Director of the Office of Postdoctoral and Graduate Student Affairs at Gladstone Institutes and is an International Officer for the National Postdoctoral Association.  Dr. Krishnamurthy earned a Bachelor’s degree in Dental Surgery, Dentistry at Ragas Dental College in India. She went on to earn a PhD in Cancer Biology and Oral Health Sciences at the University of Michigan, where she was a graduate student researcher before going on to be a full Research Scientist. She went on to be a postdoctoral fellow at the UT MD Anderson Cancer Center.  What You’ll Hear On This Episode of When Science Speaks [1:05] Mark introduces his guest, Dr. Sudha Krishnamurthy [2:09] How Sudha moved to San Francisco [3:24] Mentorship and how Sudha approaches helping students [5:28] Why graduate students should see themselves as leaders [7:45] The move towards a more holistic training program for postdocs [11:22] Support and focus for international students [15:02] Emerging trends in academia [17:02] Communication between disciplines and the growth of interdisciplinary studies Connect with Dr. Sudha Krishnamurthy Dr. Sudha Krishnamurthy on LinkedIn Dr. Sudha Krishnamurthy (@sudhakrish2) - Twitter About Dr. Krishnamurthy The importance of mentorship Great leaders inspire us to do better, go further, push harder. They can bring out the best in us, and are integral to the success of business, academia, and even the world at large. While the traits of great leadership can be natural and innate, it is usually the mentorship from another great leader which helps people to develop and grow into great leaders themselves. The students of today are the leaders and mentors of tomorrow, and they should be given the tools they need to fulfill those roles as best as they can. This is something Dr. Krishnamurthy references by discussing the programs and even courses she has been involved with which give an individualized process which helps students and postdocs discover what they enjoy doing, as well as what the possible courses their professional lives can take with their degree. The goal is to help students see what it means to be a mentor and a leader. The challenges for international students Our world is becoming smaller every day. Technology has given us connections across the world as there has never been seen in human history. Getting an education abroad is easier than ever. While immediate access to other countries has increased, there is another side which comes with it. The challenges for international students are great because cultures can be very different when someone travels to another part of the world.  Dr. Krishnamurthy has great experience as an international student, as she has gotten degrees in India as well as the United States. She is very passionate about the global reality of science and academia. As she points out, half of all the postdoc students in the United States are international students. There is an inherent need for mentorship and community for those students coming from abroad.  To know more about the important work of Dr. Sudha Krishnamurthy, and her great perspective on trust and language, make sure to listen to her full conversation with Mark on this episode of When Science Speaks. Connect With Mark and When Science Speaks http://WhenScienceSpeaks.com https://bayerstrategic.com/ On Twitter: https://twitter.com/BayerStrategic On Facebook: https://www.facebook.com/Bayer-Strategic-Consulting-206102993131329 On YouTube: http://bit.ly/BSConTV On LinkedIn: https://www.linkedin.com/in/markdanielbayer/ On Instagram: https://www.instagram.com/bayerstrategic/ On Medium: https://medium.com/@markbayer17 Subscribe to When Science Speaks on Apple Podcasts or Stitcher

Show Topic: Traumatic Head Injuries with special guest Dr. Dr. Chrisanne Gordon Co-Hosts:  Judy Gaman, Mark Anderson, Walter Gaman Guest: Dr. Chrisanne Gordon Segment 1: Today we are talking about traumatic brain injuries, a problem is becoming all too prevalent in our military. Later in the show we have a special guest Dr. Chrisanne Gordon TURN THE LIGHTS ON! A Physician's Personal Journey from the Darkness of Traumatic Brain Injury to Hope, Healing and Recovery It is estimated that 750,000 veterans from Iraq and Afghanistan struggle with the effects of mild traumatic brain injury (mTBI) or Post Traumatic Stress Disorder (PTSD), a form of brain injury. 40% - 70% will become addicted to some substance within the first year if undiagnosed and untreated. Therefore, adequately treating TBI early on will assist in curbing the opiate crisis as well as decrease alcoholism and drug dependencies. TBI patients have a greater risk of suicide. This is the END GAME for undiagnosed or improperly treated TBI. Patients with TBI are prone to unemployment which often leads to homelessness and incarceration.  DOC SHOCK Scientists at the Gladstone Institutes have unveiled a significant breakthrough in Alzheimer's disease. They proved that a blood-clotting protein called fibrinogen crosses the blood brain barrier and destroys connections between neurons in the brain (Synapses). This fibrinogen then activates the brain's immune cells. Basically that some Alzheimer's is caused by “leaky brain” (sound familiar? - Leaky Gut)  Read more! Follow us on Facebook! Tweet us on Twitter! Download the show on iTunes! Visit our website! Call us at 844-well 100 Coming up, our special Guest and brain injury specialist Dr. Chrisanne Gordon. Segment 2: Today's topic traumatic brain injury and we have a special guest coming up, Dr. ChrisAnne Gordon. Not only is the she the author of a book on head injury, she knows from personal experience how a traumatic brain injury can change your life. Immortal Minute What inspired you to write Turn the Lights On! ? Can you tell us some of the symptoms you experienced when you had your TBI? How did your TBI affect your life? Did the TBI affect your memory? How long did it take you to recover from your TBI? Did you make a full recovery? Is there a message you want to give to our listeners and others suffering from TBI? What is the goal of your book? Coming up  - the military knows TBI all too well. Our guest will walk us through the affect TBI is having on our soldiers. Segment 3: Today we're talking head injury with our special guest Dr. ChrisAnne Gordon author of TURN THE LIGHTS ON! A Physician's Personal Journey from the Darkness of Traumatic Brain Injury to Hope, Healing and Recovery How many veterans suffer from Traumatic Brain Injury? What is the percentage of veterans who will become addicted to some substance within the first year if their TBI is not diagnosed? Why do TBI patients have a greater risk of suicide? What needs to be done to help our Vets and others who are suffering from TBI? How can our lawmakers and medical community help victims of TBI? Can you tell us about your foundation, Resurrecting Lives? Where can listeners purchase TURN THE LIGHTS ON!? Segment 4: Medical Mania Trivia  - Guest Todd How many hours of sleep is recommended per night? (7.5-8) Which vitamin helps in clotting? (K) T or F. Intermittent fasting has been proven to improve cognition? (T) If someone has high VLDL what are they at risk for? (heart attack or stroke) Name one blood test that tests for inflammation within the body. (Sed rate, c-reactive protein (CRP), cCRP) DEMENTIA DEFENDER LAST WEEKS RIDDLE WAS:  I have cities, but no houses. I have mountains, but no trees, I have water, but no fish. What am I?    A. A Map This week: What is seen in the beginning of March and April that cannot be seen in the beginning or end of either month? End Show Thank you for listening to the Staying Young Show! With all the mixed messages on health, you need information that you can use and that you can trust. Listen in as the experts discuss all topics health related. It's time to STAY YOUNG and stay healthy! Each week we tackle a topic and often with leading scientists, best-selling authors, and even your favorite celebrities! As a listener of our show, your input is important to us. Please take a moment to fill out this quick survey so we can serve you better - https://survey.libsyn.com/stayingyoung2 For more information on The Staying Young Show, please visit our website at www.StayYoungAmerica.com, and subscribe to the show in iTunes, Stitcher, or your favorite podcast app. You can also reach out to our host, Judy Gaman on www.judygaman.com for book purchasing, and speaking opportunities in your area!

Host Ali Nazar interviews Shawn Lani, Director for the Exploratorium's Studio for Public Spaces, on the Bay Area institution's founding story, outreach programs, and preparations for their 50th anniversary.Transcript:Ali Nazar:You're listening to KALX Berkeley in 90.7 FM and this is Method to the Madness coming at you from the Public Affairs Department here at Calex celebrating the innovative spirit of the Bay Area. I'm your host, Ali Nassar, and today I got with me Shawn Lani, he's the Director for the Studio for Public Spaces at the Exploratorium in San Francisco. Hey, Shawn, what's going on?Shawn Lani:Hey. Nothing. Just here, jabbing this morning.Ali Nazar:Yeah, thanks for jabbing.Shawn Lani:Yeah, my pleasure.Ali Nazar:Appreciate you coming in. So we're going to talk about a few things. Exploratorium, obviously, is a beloved institution in the Bay Area, but I always ask people when we first start out about organizations like the Exploratorium, they're very unique and they start out with a kind of a problem statement in mind. What is the problem statement that Exploratorium is trying to solve?Shawn Lani:That's a good question. A lot of people think of the Exploratorium as a science museum that was formed in the way that a lot of things were formed, but the culture institutions tend to be a product of their times. They're responding to a need, and at the time, there was an educational reform movement going on in America and the 60s were happening. This is 1969, it was founded and Frank had spent many years-Ali Nazar:Frank Oppenheimer?Shawn Lani:Oh, yes. Frank Oppenheimer had spent many years as a teacher on a ranch kind of perfecting a hands-on method of learning and was convinced that people really needed a place where they can get their hands on things and figure things out for themselves. One of the things he used to do is take his kids out to a junkyard and a very non-traditional approach, take things apart, find out how they work. It was definitely a sense of the authentic was always a driving force and also a trust that people were naturally curious and could be inspired to kind of explore their own inquiry. And that turned out to be a very powerful model for teaching and learning.Ali Nazar:Yeah, and I think any of us have been to the Exploratorium totally get that feeling because that's what the place is all about. But taking just one more kind of step down memory lane, can you tell us a little bit more about Frank Oppenheimer, who he was and how he came to found the museum?Shawn Lani:Yeah. Frank Oppenheimer was Robert Oppenheimer's younger brother, he's sometimes called the Uncle of the Atomic Bomb. He worked on the Manhattan Project, and for many years after that he was ostracized from universities and ended up in a ranch in Colorado. He was a natural teacher. He was very much a humanist, and so as he spent many years out there kind of basically, surviving, he ended up coming to San Francisco. He still had a lot of contacts, a lot of people knew who Frank was and started the San Francisco Project and found the Palace of Fine Arts. He wrote up a rationale for a science museum and ended up stomping around the City Hall drumming up support for it and got a 30-year lease for a dollar a year at the Palace of Fine Arts. Ali Nazar:Wow.Shawn Lani:Yeah. That's not a bad deal.Ali Nazar:Wow, yeah, pretty good. San Francisco real estate.Shawn Lani:Yeah, exactly. Well, the funny thing is even at the time when Frank walked in that behemoth of a building, he already thought, "This isn't going to be big enough," and, in fact, we added onto that building some years later, a second floor. And then eventually, we outgrew the building altogether and moved to Pier 17 just five years ago, Pier 15, sorry, in San Francisco.Ali Nazar:Well, Great. So thank you for that story and understanding kind of where it came from. So we're almost 50 years into the Exploratorium's founding. What's the journey been like? Where are we today?Shawn Lani:Well, the Exploratorium is, I think, necessarily evolving and I think this is true of any cultural institution. They need to evolve with culture in order to respond to it and be relevant. And as we started as a science museum with exhibits that quickly grew into a explainer program that integrated teens on the floor explaining and working with visitors. We started professional development of teachers very early. We were one of the first 600 websites when that started to evolve. And so the museum's always been kind of a slowly growing institution with new feature-sets and more and more of those have become interrelated over time.And so when I think about the Exploratorium, I went there as a child, three and four years old, you kind of fall in love with the place. And even all these years later, I walk through and there's something familiar about the way that we respect humans as learners. And in everything that we do, the way that we approach the work is very much in support of somebody's own sense of wonder and inquiry and to enable people to ask questions of the world and find those questions useful and even to question the answers they get back when they ping the world. We want them to know that they are active learners, they're in control of what they understand. And so that's always kind of been a thread throughout all of our work.Ali Nazar:Yeah, and it's so fascinating to me, as I'm listening to you talk, and think about many times in this show, we have people who have started an organization six months ago or eighteen months ago. They had this dream and this vision and I've been part of founding teams too and I think one of the things that a founding team dreams of is to have something be sustainable and go on for a long time and now, we're sitting with something like that in the Exploratorium. We're almost 50 years in. How does the governance work? How do you guys keep the mission vibrant and alive and even though Dr. Oppenheimer has long since gone?Shawn Lani:Yeah, he passed in 1985. He used to say that the Exploratorium was anarchy and Frank was the anarch and there was a certain kind of a glue that he could bring just through kind of force of personality and his intellect was somebody once said, "Walking through the Exploratorium was like walking through Frank's mind," but in fact the places evolved a lot since frank has passed. And I think that was also by design because just like we've always treated visitors as part of the equation, staff has always felt like it was part of their job to generate new ideas and to figure out new ways of engaging with audiences increasingly diverse and in new ways and on subject matters that are important to them. When I first got there in '93, we were doing some work with the National Science Foundation, which is a long-term supporter.But I was kind of surprised at the number of people doing things that I didn't think at all were related to the Exploratorium. And eventually, we had a Body Show, we had shows about memory, we looked at our Light and Color and Sound exhibitions, we renamed them Seeing and Hearing, thinking more about how people are not only sensing the world but perceiving it and the acts of perception is active. You're construing, you're making sense of the world as you find it. And so reframing the world is actually a really powerful tool for allowing people to see things in a new way, and then from that moment forward, carry that with them. It's not something that happens in the museum for that moment, which is static, it's dead when you leave. You might pick up some information, but that's just information. A way of seeing the world is far more influential I think.And actually, it's far more respectful because what we don't do is say, "This is the right way to look at the world." What we do say is, "Have you thought of it this way? Have you thought about how when you look out at the Bay, say it just all looks like a bunch of water," right? But the long story behind that is where it comes from, the push and pull of the saltwater and the ecologies that live there. And once you tell that narrative, for a lot of people, I think it builds an appreciation for a way of looking at the world that's more animated. It's more animated and it's actually, it's much more fun. It's much more interesting. And so I think that's the way that we've drifted over the years as we added more and more program is how do we do that more? How do we connect with people in such a way that they feel like they're a little different from after they've brushed up against us? And likewise, I think the museum needs to feel like, "Hey, we're being changed by our visitors as well because we're in conversation."Ali Nazar:Yeah. And it's so appropriate. I think for the spirit of the Bay Area because I always think of us being kind of like the furthest on the west of the Western civilization and kind of able to question everything. That's kind of where we're at and just geographically we're the most newest of all the cities to come. And so we can kind of look back and say, "Well, should we think about it this way? Should we be thinking about it that way?" And Exploratorium really embodies that kind of spirit.Shawn Lani:Yes. It's easy to take for granted, especially if you grew up here and I know you're raising some children and once you have kids you start to realize like, "Wow, we are in the middle of so many things." We watch movies, there we are. You hear stories or you see movements come out of the Bay Area that are global. And I've been lucky enough to travel a lot because of the Exploratorium. We have a lot of global influence from the Bay Area and the Exploratorium itself. We do global consulting, we do a lot of professional development. We train over a 1,000 teachers a year. We've trained over 30,000 teachers since the inception of the Teachers Institute. And that's the kind of influence that that continues on. So those 1,000 teachers teach 15,000 students, right? There're 30,000 teachers. Think about all the kids they've reached. And all we've done is given that teacher a new tool, a way of using inquiry and informal approaches to learning about the world, and then they take it and move that forward.So that's the kind of impact I think the Exploratorium, for me, in my mind, when I think of it, I don't think of it as a place as much as a kind of movement and I think it's continuing to be a kind of movement. We occupy space in people's minds sometimes because they went there as a kid or because they bring their kids or they ... But there's something about the place that just glows, and the more we can export that glow, the better. Right?Ali Nazar:Yeah. Bottle it up.Shawn Lani:Bottle it up. Yeah. But don't commercialize it. There's that beautiful blend of sharing. It's a kind of sharing.Ali Nazar:Yeah. And the amplification effect is so much what's so special about founders in my mind is someone has this idea in their brain and if they're successful, like Dr. Oppenheimer was, look at the amplification effect and how many lives he's touched just because he pursued that thought in his brain of, "Well, people should have experiential learning."Shawn Lani:That's right.Ali Nazar:And look what's happened since 50 years later.Shawn Lani:That's right.Ali Nazar:And it's really amazing. So we're talking to Shawn Lani, he's a Director for the Studio for Public Spaces at the Exploratorium in San Francisco right here on Method to the Madness on KALX Berkeley 90.7 FM. Shawn, so let's talk a little bit about the Studio for Public Spaces. So there're lots of programs there, but before we get into that, I want to just get a little bit of your background. Tell us about yourself.Shawn Lani:Well, I grew up in the Bay Area primarily. I was born in San Leandro, lived in Oakland and so definitely a Bay Area person. I was lucky enough to spend a lot of time out on a ranch in eastern Nevada and was inspired by just the raw nature of that landscape. And, in fact, it brought a lot of that work into the Exploratorium and that way of seeing those landscapes. And I studied at Davis and really enjoyed English and art history. I studied a lot of things. And the funny thing was I wasn't a science guy. I was handy and I could fix things on the ranch, but mostly when I was supposed to be digging holes, I was staring at springs or watching birds and so it wasn't a great rancher either.So somehow I landed up, ended up at the Exploratorium. I got a Masters in Museum Education and Design at John F. Kennedy University. And I just never thought I could work in a place that wonderful. I didn't even think to apply and it popped up, but it seemed faded. I lived only three blocks away from it. I was just extremely lucky to find it and that place changes over time. We've gotten a lot bigger and its mission has shifted not unnecessarily. And I was able to slot into a place and then move through the museum and experience what the global impact is like, what it's like to work locally. And then in 2008, we opened a show at Fort Mason. It was an outdoor Exploratorium and rather than introducing phenomenon like we do in the museum, we capture it out there.We framed it and we looked at the landscape as kind of a subject matter and tried to do these conceptual framings that allowed people to see the world in a new way and was really hooked, really fascinated with the idea that you didn't have to go inside the museum to have a really poignant experience. And, in fact, I was struck by how different it was. I wouldn't say better, but having it be a part of your daily life seemed to make it much more accessible and far more interesting as a developer, as a designer because then it's like you're in the ultimate a flea market, right? Like, "What's that? How did that happen? What the?" All these questions come to mind and sometimes when you dig a little bit, you find the most amazing answers. We're curious, Pete Richards, a senior artist at the museum, he'd heard the Golden Gate Bridge moved up and down because of the heat.So we put a GPS tracker on it. We talked to Leica. We really did our research and it turns out, sure enough, it moves up and down a foot or two depending on the temperature of the day. And there's kind of a mean temperature in the middle. So we put a scope on the bridge from a mile and a half and actually, it's three miles away with a little line in the middle. And we called it a bridge thermometer if it was a hot day, the bridge would be low and it was a cold day, the bridge would be up. And it was just such a lovely kind of observation that Pete had brought along. And then we were doing evaluation later and a runner came by and she stopped and she looked at it and she took off and our evaluator chased her down and said, "Well, that's usually not a good sign if somebody just does a glancing blow."And she said, "No, I just like to see where the bridge is every day when I went by, I want to see what the bridge is doing." So it was such a wonderful thing to think of reframing that big static thing in the distance, not as kind of a thing that doesn't move, but a thing that's being responsive to temperature. When the sunrises, it takes a couple hours for the bridge to heat up and sag. So there's all these beautiful thermodynamics going on and it's that kind of animation that really caught our attention.Ali Nazar:That's super cool. I mean it reminds me of just in such a hyper-creative environment of almost in I would think like Saturday Night Live where you have all the writers around pitching ideas. There're like lots of ideas. How does it work? Because I would think that the staff there is super-creative and comes up with all sorts of interesting thoughts like that.Shawn Lani:Yeah.Ali Nazar:How does the process of getting something approved and funded go?Shawn Lani:Well, we prototype a lot and you might have an idea, but if you don't test your idea, nobody's going to believe you. And the ultimate test is how the public responds to it in the final form. And so one of the things we do, we utilize evaluation in a more formal way but also in an informal way. We tinker about, we try things. And that's true of most subject matters. Even as we move into the social sciences and thinking about stereotypes and thinking about how do you exhibitize some of those experiences? You don't really know until you go out and you try it with people. And the beautiful thing about that isn't that there again to prove or disprove what you thought was right they're most likely going to inspire you to do something that you wouldn't have otherwise thought of. That collaborative effort extends far beyond your immediate development team. I mean we might beat each other up about whether we think it's a good idea or not, but that kind of healthy criticism can only really be verified by the end-users.Ali Nazar:Sure, which is very much part of the spirit of San Francisco tech life. Lean startup and 20th-century design, hi-tech.Shawn Lani:Starting in '93 there was no tech, there was no ... I didn't have a computer on my desk. If you wanted something, you called the old guy that worked at the part shop and you told him what you needed, right. But the language started to come from tech eventually started to seep and some of it was familiar and some of it sounded kind of, I wouldn't say naive but there was the beginnings of that ... Because that kind of iterative culture, the prototyping culture takes a long time to get good at. Not 20 years, but a few years, and the lessons that tech learned sometimes it's in this much shorter cycle so they'll learn part of the lesson. But the full lesson really is, I think, it goes to the maturity of an organization and as a creative person and who's able to work with others and also listen, it's not an easy thing, but when you get it right, you understand why it works.Ali Nazar:Yeah. Well, so back to your story, so you joined in 1983. It sounds like you just lucked into the perfect job for you, which is congratulations.Shawn Lani:Yeah. Yeah.Ali Nazar:You've been there for a long time now, so that's awesome. So you're right now on this Studio for Public Spaces project. So tell us about that and how it came to be.Shawn Lani:Yeah. So as an exhibit developer, back then, you would develop exhibits for the floor for people have experiences they learn from those. It was something that you learned. It took about five or seven years I got my chops. And that project at Fort Mason was interesting because we had this kind of instrumented landscape, right? You can walk through and experience it, but what I think we missed, I found out later with subsequent projects, is that places have people in them and those people are part of that landscape. That social landscape is also the raw material of future experiences, future exhibits, you can instrument the landscape, but you can also help instrument people's behaviors and how they're moving through the world. And so after we opened Pier's 15, 17 we did the first living innovation zone on market street.And that was through the Mayor's Office of Innovation with Mayor Lee. And we worked with Neil Hrushowy over in city planning and Paul Chasan and others. And it was a remarkable experience because we put a pair of listening vessels, which are eight-foot-tall dishes done by Doug Hollis on Market Street. At the Yerba Buena Lane and nobody really knew what to expect, including us. But we had this notion that that inquiry's a natural kind of social lubricant and that there were lots of rules on Market Street. We know this, right? You don't look people in the eye, you don't talk to anybody, you don't put your bag down. It's like a human freeway. Right? So we put these listening vessel's kind of diagonal to that freeway and people really responded. I think they responded in a better way than I had even hoped.They were willing to talk to strangers. They were kind of joyous and celebratory. They would watch each other play and figure this thing out. They tried to find out where it was plugged in. So these dishes, you can whisper in these dishes and hear each other from 50 feet away very clearly. And it's also very intimate because it sounds like somebody's just in your ear because the way the sound is focused with the parabolic dishes. And so after that, the Studio for Public Spaces was founded with the goal of bringing more of these inquiry-like experiences to public spaces because the audience is vast. The impacts are amazing really in terms of how it shifts people's behavior in real-time, in real space in cities. And so since then, we've done many projects throughout the Bay Area, San Leandro. We're working on a project currently on Fulton Street between the Asian Art Museum and the library across from City Hall.And to bring this methodology work the way they explore terms work traditionally the prototyping, the integration, the respect for the learner to a public space. And I think especially with social sciences, understanding how we construe the world, what science can teach us about how we understand things and how and why we process the world. Exploring that in a public space, especially when it challenges you in Plaza and The Civic Center, it's improving. There're a lot of things going on there now, but there's also a lot of friction. It's right in the middle of it. I mean you had to put a pin in San Francisco and say, "Where's the middle of it?" It's right there. And it's a powerful medium to be in. And I'm exploring topics like how do we categorize it? Why do we so immediately categorize people? Why do we stereotype folks? What biases are driving ourselves? This is all a way of thinking about the human mind.What you know of the world is directly proportional to what you know of yourself. And to understand how we're thinking on a meta-level is incredibly empowering because it allows you not to be a victim of your own fast-twitch thinking. You can slow down and you can reconsider. You can look for the options when you look at a scene. Not only, "This is what I think about what's happening," but, "Why am I thinking that and what other alternatives might there be?" So it's been fascinating and I think also humbling to have such a dynamic mix of emotions, cultural issues, and then trying to do this place-making maneuver in the middle of a place that is kind of inherently inhospitable.Ali Nazar:We're speaking with Shawn Lani, he's the director for the Studio for Public Spaces at Exploratorium Museum in San Francisco here on Methods of the Madness on KALX Berkeley 90.7 FM. I'm your host, Ali Nassar, and Shawn, so you're talking about different projects that you might be doing in different municipalities across the Bay Area. So take me through how does that work? I mean, this sport team can't just parachute in, "Hey, we're going to do this," right. "Get out of the way."Shawn Lani:That's the worst case, man. You never go where you're not invited. That's the rule.Ali Nazar:How do you guys build these projects?Shawn Lani:Yeah. They're very complex networks of partnerships. So that city is one level, but we also have formal relationships with the Gladstone Institute, NASA, the Smithsonian, UC Davis, UCSF. We've worked on the Resilience by Design design challenge with Tom Leader through the Bay Observatory. And so those networks have been forming over the last 50 years, literally. And I think the last 30 and even 20 years, we've really accelerated that partnership. There're strategic partnerships, meaning that we have partners where we benefit from each other's expertise. And we've always brought in a lot of Ocher Fellows, which is a program where we have visiting scientists who've had Nobel laureates, we've had Poet Laureates, right? We've had MacArthur Geniuses, four or five of those coming through the program in order to do enrich the work.And I think that's the natural mode for the museum now is to have many, many receptors. Because what we can do, I think, is make some of that really important work, especially when it comes to the environment, environmental issues. We can provide a platform for people to understand that the complex issues that are going on around them, and a way of sorting through the information and figuring out what they think is important and not telling them what's important. It's not that kind of advocacy. It's advocacy for the visitor to feel like they understand what's happening. So they could make a more informed decision, which is very much about one of the tenants of Frank's founding, the Exploratorium was we need an informed citizenry to have a healthy democracy. You can't have it without that.Ali Nazar:Now, more than ever.Shawn Lani:Now, more than ever. And I think the need continues to increase. It's never gone away. And the notion of learning is what the body of work that we learn about is a bunch of facts. That's not true. It's the cultural pursuit of what we collectively value and that shifts over time. So only through partnerships and only through this way of thinking can the Exploratorium remain relevant. So with our work in the Studio for Public Spaces, we're working with urban planning. We work with the mayor's office, we worked with REC and Park, we work for the Trust for Public Land. We work with other people that are invested in public spaces. So oftentimes there're community groups, groups like Green Streets over in Buchanan Mall, Citizen Film.They're smaller nonprofits, but they play an incredibly important role as guides in how to make this work. And guess what? Mayor Lee used to say for the first [inaudible], "We're going to make this a bureaucracy-free zone, so you guys going to come in and do ... So it turns out it was actually bureaucracy-light. There was still a lot of bureaucracy.Ali Nazar:Yeah, that was aspirational.Shawn Lani:Yeah, it was aspirational, but you got to reach and it got us in, right? It got us the gig. But to be able to go through those permitting processes with DPW or with MTA and have a good working relationship and even watching those departments bend a little when they're not totally sure it's going to be okay. I think it's really a hopeful sign. I mean there are so many good smart people working in city government. I know that sounds crazy, but I am shocked at how dedicated they are and how willing they are to bend a little and to help things that might not be known as this is going to be a total success. But the way we work is two-year pilot projects very often. It's worth the risk to find out does this help? Are we prototyping a way for the city to work in the future and what can we learn from this lesson? It's heartening to see how many people will support that kind of activity.Ali Nazar:Yeah, I think so much as to do with the vision. So we had Ben Davis on the program who was the thought leader behind the Bay Light Shore Bay Bridge. He had to get a few different municipality organizations together to make that happen. But the vision was so strong and everybody loved that bridge. So they were like, "Yes." Like, "I get it, we want to do it," and I think you guys have that power too because you have a vision that people, like you said, you feel it's not just about when you're at the museum, it's about the next day or that night.Shawn Lani:Right.Ali Nazar:I feel that with my kids when we take them there because we're members of the Exploratorium and they talk about it for a few days afterwards, "Remember that thing? Remember that thing?" And it's a vision that's so powerful that I think is galvanizing for people to get behind.Shawn Lani:Yeah. I always joke, "It's almost a cheat when you come into a situation that's in a public space." The Exploratorium comes and like, "Oh, you guys are here." Oh, he's always so happy to see you. Like, who's going to fight with Exploratorium? Like, "We don't fight. We just want to come here and have some fun and talk about things," and so it really is a leg up to build on that many years of goodwill and tradition and I think that's super important. When it comes to brand value, people don't want a brand the Exploratorium has always striven or strived, striven? Stroven?Ali Nazar:Strove? [inaudible].Shawn Lani:Thank you. To be authentic, it doesn't lie to people. I mean, I remember, this is how crazy we can get. If you have a box of wires, it's always a question whether or not you could make it out of plexi or you should make it out of wood because if you can't see it, you might not trust that it's not just going through or connecting up. So oftentimes we'll reveal the back of an exhibit just so people can kind of test it. And I wish government was like that actually, that radical transparency, right? "Is it doing this?" And like, "I don't know, try it out." I mean if you can't tell, that's not a good exhibit. Right?That's not a good experience if you're wondering, you're scratching your head and wondering if somebody just put one over on you. And so we have always tried to have that kind of relationship and that really pays off when we go for partnerships. They sense that we're not going to get between what it is that they think is important and what they're trying to show and what the visitors are going to take in. We're all about facilitating that understanding.Ali Nazar:Well, it's, it's super cool work that you're doing and thanks for coming in this morning. I do want to ask you just next year's the 50th anniversary?Shawn Lani:Yeah.Ali Nazar:So it's such an amazing institution that we're all proud of in the Bay Area. What can we expect for next year to happen at Pier 15 or across the Bay Area?Shawn Lani:Well, we'll be opening the Social-Psychology show in July of 2019 and so that is going to be 12 to 14 exhibits outside Public Space Installation and that's going to be paired with a show about identity at the Exploratorium. This is a really interesting move I think for the museum to move into the social sciences because they're not traditionally easy to approach. But I think they are incredibly relevant, given the time. And so those are going to be two peak ... Now, we also have a lot of ongoing programming about the environment and ecologies. So we have conversations about landscapes, we have Lab and Lunch.We just hosted the climate summit, several talks about the climate summit, so we're going to be continuing that work moving forward. And also our After Darks, are every Thursday nights and those are heavily programmed. So we're kind of like a piece of broccoli in that way. You have the broccoli sprout but then you have a lot of other little things going on and then you have a lot of other things going on. But those are some of the big lobes but there's lots of other stuff going on as well.Ali Nazar:Okay, I'm sure everybody knows how to get ahold of the Exploratorium, so how about for the Director, for the Studio for Public Spaces? If people want to learn more about that, how would they learn more about it?Shawn Lani:Well, just type in Studio for Public Spaces at the Exploratorium, and you'll see the website that has a list of our projects and also a lot of the thinking and the framing of the work. We have some publications there as well, and an ongoing blog.Ali Nazar:Okay, well, great. Well, we've been talking to Shawn Lani this morning, the Director for the City for Public Spaces at the Exploratorium in San Francisco. Shawn, thanks for coming in.Shawn Lani:Oh, my pleasure. Thanks so much.Ali Nazar:And you've been listening to Method to the Madness on KALX Berkeley 90.7 FM, University of California, a listener-supported radio. I'm your host, Ali Nazar. Thanks for listening everybody and have a great Friday. See acast.com/privacy for privacy and opt-out information.

Show Topic: Opioid Addiction – Protect Yourself and Your Family Co-Hosts:  Judy Gaman, Walter Gaman, Mark Anderson Guest: Gene Mosely in studio Segment 1 Opioid addiction is an epidemic in this country and it can happen to anyone. If you want to stay young and stay healthy, you need to stay informed. That is why we chose to do an entire show dedicated to Opioid addiction and how you can protect yourself and protect your family. We have a special guest in the studio with us today Gene Mosely who shook off the at-risk youth label and became an All-American Collegiate Scholar, Two-Time College Graduate, Certified Teacher, and Certified Behavior Change Specialist who now speaks to crowds around the country on a number of topics, including Opioid addiction. Opioids: a class of drugs that include the illegal drug heroin as well as prescription pain relievers such as oxycodone (OxyContin®), hydrocodone (Vicodin®), codeine, morphine, fentanyl, and others. Natural Opiates: Natural opiates are from the poppy plant in its purest forms. Some of the more commonly known natural opiates include: Morphine, Codeine, Thebaine, Opium Deaths from Opioids has quadrupled since 1999. In 2016 the CDC reported 42,000 deaths How it began – 1990s push for doctors to treat pain as the 5th vital sign and pharmaceutical companies were pushing opioids as a non-addictive solution for pain. According to the CDC, by 2015 there were enough prescriptions for opioids to medicate every single American for at least 3 weeks. 80% of Americans who now use heroin said they started with an opioid prescription Read more at http://thehill.com/homenews/politics-101/376508-what-caused-the-opioid-crisis MUSIC FOR DOC SHOCK (JIM) THAT MUSIC MEANS IT'S TIME FOR DOC SHOC. A TIME WHEN WE FIND SOMETHING SHOCKING IN THE NEWS OR WE'RE SHOCKED IT MADE THE NEWS. Researchers at the Gladstone Institutes in San Francisco, CA may have found a cure of Alzheimer's disease. You can find the full study published in the journal Nature Medicine. The faulty APOE4 gene seems to be the genetic variation most harmful to the brain.  The researchers found that applying an APOE4 structure corrector, they were actually able to reverse the signs and symptoms of EPOE4- related Alzheimer's Disease.  Read the study! Follow us on Facebook! Tweet us on Twitter! Download the show on iTunes! Visit our website! Call us at  844-well 100 When we come back, our special in studio guest, Gene Mosley will take you through what you need to know to protect yourself and your family from Opioids. Segment 2 Today's show is all about opioid addiction and how you can protect yourself. Coming up we will be taking with Gene Mosley, an expert on opioid addiction and behavior change. ANDERSON - Immortal minute – 2 min. How people become addicted How youth get Opioids Emotional Withdrawal from Opioids How to help prevent youth from getting Opioids Reasons youth take Opioids Docs – how easy it is for adults to become addicted post-surgery Tease 20 sec. –www.stayyoungamerica.com SHOUT OUT TO MILITARY, Facebook (stay young media group) , download podcasts – follow us on twitter @StayYoungMedia coming up  - what you should do with your old prescription pain medications – flushing them is not the answer. Segment 3 Judy – Tease the upcoming Dementia Defender 844-WELL100. Podcast has over 2 ½ million downloads! This whole hour we have had behavioral change specialist and national speaker, Gene Mosley in the studio with us. Our focus today is opioid addiction and you can protect yourself and your family Giving used medications to Police Station Purpose of Opioids Gene's experience in the Wellness Industry dealing with adults addicted to Opioids. Open discussion Judy tease DD – grab a pen!  844-well100. Podcasts itunes, stayyoungamerica.com – 45 sec. Segment 4 Tease DD 844-Well100 – If you're just tuning in, catch this and every episode on iTunes under Staying Young Show 2.0 or follow us on TWITTTER @StayYoungMedia  Medical Mania Trivia – Trivia @ 1:40 Bill Do muscles work alone or in pairs? (in pairs so that they can pull in different or opposite directions) ¼ of your bones can be found where? (In your feet) T or F Pound for pound a baby is stronger than an ox. (T) On million ____ filter out liquids and waste in the kidneys. Nephrons, Neurons, or Axons (Nephrons) What body shape is most associated with diabetes? (Apple) Open discussion DEMENTIA DEFENDER -THIS DEMENTIA DEFENDER IS BROUGHT TO YOU BY SMART NEW YOU AND DR. CHARLES POWELL. IF YOU HAVE SLEEP APNEA AND YOU'RE READY TO DITCH YOUR C-PAP MACHINE CALL 214-524-6333. “WE have had several people call in and ask us to reveal the answer to the last show. THE ANSWER TO LAST WEEKS RIDDLE WAS –  the lion. If he hadn't eaten for 3 months he'd be a dead lion! Two Scientists Walk Into A Bar. One Asks For H2O, The Second Asks For H2O, Too. Which Scientist Dies? End Show Thank you for listening to the Staying Young Show! With all the mixed messages on health, you need information that you can use and that you can trust. Listen in as the experts discuss all topics health related. It's time to STAY YOUNG and stay healthy! Each week we tackle a topic and often with leading scientists, best-selling authors, and even your favorite celebrities! As a listener of our show, your input is important to us. Please take a moment to fill out this quick survey so we can serve you better - Survey For more information on The Staying Young Show, please visit our website, and subscribe to the show in iTunes, Stitcher, or your favorite podcast app. You can also reach out to our host, Judy Gaman on www.judygaman.com for book purchasing, and speaking opportunities in your area!

Phil and Stephen review more reasons that this is a great time to be alive. The little lizard with the big genome. Making skins cells into stem cells -- three different ways! The check-in procedure that could save your life. PLUS Geekout: deciphering the Voynich manuscript via AI. The Smiling Axolotl Hides a Secret: A Giant Genome Scientists have decoded the genome of the axolotl, the Mexican amphibian with a Mona Lisa smile. It has 32 billion base pairs, which makes it ten times the size of the human genome, and the largest genome ever sequenced. Axolotl genome sequenced, revealing regeneration genes Researchers create first stem cells using CRISPR genome activation In a scientific first, researchers at the Gladstone Institutes turned skin cells from mice into stem cells by activating a specific gene in the cells using CRISPR technology. The innovative approach offers a potentially simpler technique to produce the valuable cell type and provides important insights into the cellular reprogramming process. Google is using 46 billion data points to predict the medical outcomes of hospital patients Some of Google’s top AI researchers are trying to predict your medical outcome as soon as you’re admitted to the hospital. GEEKOUT Artificial Intelligence May Have Cracked Freaky 600-Year-Old Manuscript    WT 402-715 Eternity Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 License creativecommons.org/licenses/by/3.0/

Eric Verdin is the president and chief executive officer of the Buck Institute for Research on Aging. The institute, based in Novato, Northern California, is America's first and largest independent body focussed on the biology of aging. Until recently, Dr. Verdin was a senior investigator at the Gladstone Institutes, in San Francisco, where he studied the role of metabolism and diet in aging. A world-renowned expert in the field, Dr. Verdin is trying to better understand the mechanisms linking caloric restriction to increased health span and longevity.

Dr. Carolyn Lam:               Welcome to Circulation on the Run. Your weekly podcast summary and [inaudible 00:00:06] of the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. In just a moment we will be discussing really fascinating preclinical data to suggest that high fiber diet and acetate supplementation may change the gut microbiota and thereby prevent the development of hypertension and heart failure. But first here's your summary of this week's issue.                                                 The first paper describes the impact of heart transplantation on the functional status of children with end stage heart failure in the United States. First author, Dr. Peng, corresponding author Dr. Almond and colleagues from Stanford University, use the organ procurement and transplantation network to identify 1,633 US children age less than 21 years, and surviving one year or more post-heart transplant, from 2005 to 2014, with a functional status score available at three time points. Namely at listing, at transplant, and one year or more post-heart transplant. They found that at the one year assessment 64% were fully active with no limitations, or a functional status score of 10. 21% had minor limitations with strenuous activity, or a functional status score of 9. And 15% scored a functional status score lower than 9. Compared to the listing functional status, functional status at one year post-transplant increased in 91%, and declined or remain unchanged in 9%. Early rejection, older age, African-American race, chronic steroid use, hemodynamic support at heart transplantation, and being hospitalized at transplantation, were all associated with abnormal functional status post-transplant.                                                 These findings may be helpful to patients, families, and referring providers by providing a contemporary picture of the post-heart transplant life in children as they weigh the risks and benefits of transplantation.                                                 The next paper brings cardiac reprogramming one step closer to clinical translation. In this paper by first author Dr. Mohamed, corresponding author Dr. Srivastava, and colleagues from Gladstone Institute of Cardiovascular Disease in San Francisco, the authors used a high throughput chemical screen in post-natal mouse cardiac fibroblasts, and found that transforming growth factor beta, or TGF beta, and WNT, or wint inhibition, enhanced transcription factor based direct reprogramming of cardiac fibroblasts to induce cardiomyocyte like cells in vitro and in vivo. A combination of TGF beta and wint chemical inhibitors increased the quality, quantity, and speed of direct reprogramming, resulting in improved cardiac function after injury as early as one week after treatment. These chemical inhibitors enhanced human cardiac reprogramming and reduced the number of transcription factors needed for human cardiac reprogramming to just four factors. These findings if validated in large animals could facilitate a combined gene therapy and small molecule approach to heart failure.                                                 The next study is the first report of the risks of cardiac mortality among five year survivors of childhood cancer beyond 50 years of age. First author Dr. Fidler, corresponding author Dr. Hawkins, and colleagues from University of Birmingham in United Kingdom, looked at the British childhood cancer survivors study, a population based cohort of 34,489 five year survivors of childhood cancer that was diagnosed from 1940 to 2006 and followed up until February 28th in 2014. The authors quantify the cardiac mortality access risk. Overall 181 cardiac deaths were observed, which was 3.4 times that expected. Survivors were two and half times more at risk of ischemic heart disease, and almost six times more at risk of cardiomyopathy or heart failure at death than expected. Among those aged over 60 years, subsequent primary neoplasms, cardiac disease, and other circulatory conditions accounted for 31%, 22%, 15% of all deaths. Specifically for cardiomyopathy or heart failure deaths, survivors diagnosed between 1980 and 1989 had 29 times the excess number of deaths observed per survivors diagnosed either before 1970 or from 1990 onwards. Thus the authors concluded that excess cardio mortality among five year survivors of childhood cancer remains increased beyond 50 years of age, and has clear messages in terms of preventative strategies. However, the fact that the risk was greatest in those diagnosed in 1980 to 1989, suggests that initiatives to reduce cardio toxicity among those treated more recently may be have a measurable impact.                                                 The last study describes the 30 day results of the Source 3 Registry, that is the European Post Approval Registry of the latest generation of the Sapien 3 trans-catheter heart valve. Dr. Wendler and colleagues from King's Health Partners in London, describe that these 30 day results of the Source 3 Registry demonstrate that trans-catheter uratic valve implantation, or TAVI, using the Sapien 3 resulted in high procedural success with low procedural complications, and excellent post-implant hemodynamics. Moderate to severe paravalvular leakage appeared to be lower with the Sapien 3 than reported with prior versions of this trans-catheter heart valve. Rates of pacemaker implantation were higher with the Sapien 3 than in earlier generations of the valve. This, in combination with the growing experience of patient selection, procedure planning, execution, and post-operative care has led to one of the best short-term outcomes ever reported after TAVI. These results are discussed in an accompanying editorial by Dr. [Altassi 00:06:58], and Dr. [Urani 00:06:58], from the Emery Midtown Hospital in Atlanta, Georgia, where they say that these early results from Source 3 Registry are a source of encouragement with some caveats.                                                 Well, those were your summaries. Now for our feature discussion.                                                 I am so honored to have two lovely ladies join me today on the show. And they are the first author of a feature paper, Dr. Francine Marques from Baker Heart and Diabetes Institute in Melbourne, Australia, as well as Dr. Peipei Ping, associate editor from the David Geffen UCLA School of Medicine. Welcome ladies. Dr. Peipei Ping:                 Hi, hello. Dr. Francine Marques:   Hi, thank you for having us. Dr. Carolyn Lam:               As a clinician, I have very very often advised my hypertensive patients to go on the dash diet. And you know, I have no had any trouble explaining the low salt bit, right? I understand it. But then I realize that I've always advocated as well the high fiber bit, not actually really understanding how high fiber directly impacts blood pressure. And I'm so excited because your paper, Francine, shed some light on this and it actually has something to do with the gut. So could you please explain what you did and what you found? Dr. Francine Marques:   So we fed a mouse model called [adoca 00:08:25] model of habitation, that also developed heart failure, we fed them a high fiber diet for three weeks, and then after that we did a surgery to make them become [habitant 00:08:36] safe and we followed them up for six weeks. And what we observed through that trajectory is that mice that were fed a high fiber diet had significantly lower systolic and diastolic blood pressure, and also an improvement in the heart function, and also a decrease in both heart and brainal fibrosis. And the reason why the fiber is so important is because although we usually don't digest the fiber, the bacteria in our gut absolutely love it. And that allows the bacteria, good bacteria to grow. And with that growth we have release of the fermentation of the fiber, releases in short chain fatty acid. So these specific molecules can then be put back into our body and can help us in our health. So we also fed these mice acetate, which is one of the short chain fatty acids, directly and we also observed very good improvements in blood pressure and cardiovascular health. Dr. Carolyn Lam:               It's just fascinating. So these are studies in mice. What do you think of clinical translational aspects of this? Dr. Francine Marques:   Large epidemialogical studies have shown that there is an inverse correlation between fiber consumption and blood pressure. And they have seen this through very small clinical trials looking into the intake of fiber lowering blood pressure. But our study opens the possibility of new interventions using maybe short chain fatty acids specifically, but are also looking into a different type of fiber. So most studies would look into either soluble or insoluble fiber directly. Our study, the diet that we used, is mostly resistant starches. So these are their preferred type of fiber for bacteria growth in our gut. And maybe they use a [inaudible 00:10:32] type of fibers as well could be a new [inaudible 00:10:36] opportunity. Dr. Carolyn Lam:               Peipei, I remember you discussing this paper at our editorial meetings and you so beautifully highlighted the novelty of this paper. Could you share this with our listeners? Dr. Peipei Ping:                 Often within many complex studies trying to understand cellular pathways and mechanisms of cardio protection, it's a very important topic as we have had our research focus on in the pas t 25 years. What's very unique and provocative of this particular study is that it simply identified critical metabolic pathways that actually is underlying the protective effects. Many of us have wondered about with eating, for example vegetables or high fiber diet, it is examined specific molecules that have both a direct as well as an endocryne path that would circulate things back to the cardiac muscles, and having the muscles becoming more protective because of regulation of certain transcriptomic pathways to support cardiac muscle contraction. So we were very impressed by both the new concept as well as the state of the art technologies employed in this investigation. Dr. Francine Marques:   Thank you, that's very nice. Dr. Carolyn Lam:               I couldn't agree more, you put it so beautifully Peipei. I thought that it was really nice also linking pathways as well as linking several organ systems. Is there anything you might want to highlight about the renal effects, not just cardiac? Dr. Francine Marques:   Yes. Many times investigations been focusing on if something went wrong how do we cure it? More precious is when we find novel results telling us the healthy individuals, what are the things we should be doing so our blood pressure would stay at the normal level, or our cardiac function is being protected if there's an insult or injury. And so in this situation, the examination of the entire renal transcriptomic do give us very valuable information on how the blood pressure regulation system that maybe actually protected by the short chain fatty acid acetate. Dr. Carolyn Lam:               So true Francine. Anything else to add? Dr. Francine Marques:   Just to say circulation, for giving the opportunity to submit this paper, and share it with the world. We're very very excited about the data. Dr. Carolyn Lam:               Yeah we should be the ones to thank you. It's a beautiful paper. We're very privileged to publish it in circulation. May I ask what are next steps for you? What do you think needs to be done from here? Dr. Francine Marques:   We're validating this in other models now. And we're also looking into the [inaudible 00:13:57] microbiome and how that's related to habitation. So trying to really pinpoint mechanisms and how we can move this forward into the clinic. Dr. Carolyn Lam:               That's so great. And Peipei, do you think that there's certain gaps that urgently need to be addressed now? Dr. Peipei Ping:                 Yes, I think one of the most beautiful thing that ... Concept, illustrated this investigation is we really couldn't be just focusing on one organ, our primary interest organ, heart, alone. What's demonstrated here is a beautiful link of both mechanism as well as governed by transforming parbolytes with endocryne effects. How the gut, the kidney, and the heart are all connected together in this process, achieving a better protective condition in the environment for the cardiac muscle. Dr. Carolyn Lam:               Thank you listeners. You've been listening to Circulation on the Run. Tune in next week for even more news.  

Elijah Martin is a second year graduate student in the Developmental and Stem Cell Biology program at University of California, San Francisco (UCSF). He works in the laboratory of Dr. Deepak Srivastava at the Gladstone Institutes where he studies how the heart forms to try to understand causes of heart disease in order to develop therapies. In the lab, Martin grows heart cells in petri dishes, which involves mixing together different chemicals and nutrients to get the cells to grow and develop into a heart. He also uses microscopes to track the growth of the cells. Since he was a young child he has wanted to study the heart, and going to graduate school can help turn his dream into a career.

Growing a human heart from a single cell may seem like science fiction, but scientists at the Gladstone Institute at the University of California San Francisco, have taken a huge step forward, by producing the first three-dimensional, beating, human heart chamber. Previously, it had been possible to produce a two dimensional sheet of beating heart cells, but to really gain an understanding of heart formation in a developing foetus and perhaps more importantly, how drugs given to women during pregnancy may affect this development, a three dimensional structure was needed. By treating stem cells... Like this podcast? Please help us by supporting the Naked Scientists

Growing a human heart from a single cell may seem like science fiction, but scientists at the Gladstone Institute at the University of California San Francisco, have taken a huge step forward, by producing the first three-dimensional, beating, human heart chamber. Previously, it had been possible to produce a two dimensional sheet of beating heart cells, but to really gain an understanding of heart formation in a developing foetus and perhaps more importantly, how drugs given to women during pregnancy may affect this development, a three dimensional structure was needed. By treating stem cells... Like this podcast? Please help us by supporting the Naked Scientists

Researchers at the University of California, Berkeley and the Gladstone Institutes have grown beating cardiac tissue from stem cells in work that may lead to new ways to quickly screen for drugs likely to cause birth defects in the heart and identify drugs that may be dangerous during pregnancy. We spoke to Bruce Conklin, a senior investigator at the Gladstone Institute of Cardiovascular Disease, about the work, which was published in the journal Nature Communications, the promise it has for providing more accurate insights than animal models, and whether the approach could be expanded to other cell types to screen for drug toxicity to other organs.

On October 1st, 2013 CIRM, the AIDS Research Institute, and the Gladstone Institutes sponsored an informative, interactive Town Hall forum on HIV cure research in San Francisco's State Building. The event included a panel discussion by a distinguished lineup of scientists, clinicians, and advocate who provided the latest news in cure research from HIV conferences, the Martin Delaney AIDS Cure Research Collaborative, the biotech industry, and the California Institute for Regenerative Medicine (CIRM). Series: "California Institute for Regenerative Medicine" [Health and Medicine] [Show ID: 28244]

On October 1st, 2013 CIRM, the AIDS Research Institute, and the Gladstone Institutes sponsored an informative, interactive Town Hall forum on HIV cure research in San Francisco's State Building. The event included a panel discussion by a distinguished lineup of scientists, clinicians, and advocate who provided the latest news in cure research from HIV conferences, the Martin Delaney AIDS Cure Research Collaborative, the biotech industry, and the California Institute for Regenerative Medicine (CIRM). Series: "California Institute for Regenerative Medicine" [Health and Medicine] [Show ID: 28244]

Each summer, The Gladstone Institutes places high school students in some of the best labs for the study of heart disease, brain disorders, virology and immunology. The students work alongside scientists where they learn to conduct cutting-edge experiments, This past summer, we teamed up with Gladstone to mentor two of the students, Hanan Sinada and Kainat Shaikh. After their day in the lab, they met with our producers Kate Woronowicz and Yelena Kulik to learn how to create a podcast episode about their experience. Today’s episode is written and produced by Kainat, a student at Burton High School. Kainat shares what she learned about HIV, what she called “The Sneaky Intruder".

Phase II: Concept Art from Mike Minor's Drawing Board In 1977, Paramount Pictures envisioned a new five year mission for the Enterprise. Although illustrator Mike Minor (who also worked on TOS, The Motion Picture and The Wrath of Khan—and who was the uncredited creator of "The Tholian Web"—created concept art for the project, titled Phase II, the show was never realized. However, several pieces of Minor's concept art for the show have recently been released, showing designs for engineering, the captain’s quarters, a cargo hold, and a recreation room. View Minor's Phase II artwork on ScienceFiction.com.   Making Dr. McCoy's Magic Pills Real When the crew of the Enterprise traveled back to 1986 San Francisco, the most shocking thing to Bones wasn't chaotic traffic or computer input via mouse, it was the primitive state of medicine. Taking inspiration from Star Trek, doctors today are working to make things like Dr. McCoy's magic pills—which apparently grow new kidneys. A breakthrough by Gladstone Institutes allows scientists to transform skin cells into heart muscle cells, which could eventually lead to the development of Star Trek-like treatments for a wide range of ailments.    Read the full Treknosis column on StarTrek.com

Dr. Andrews-Zwilling discusses more about dementia, Alzheimer's and what to expect in the coming years. She has established her own research program to develop drugs that block the detrimental effects of apoE4 on nerve cells in collaboration with Dr. Robert W. Mahley at the Gladstone Institute.

Dr. Andrews-Zwilling discusses more about dementia, Alzheimer's and what to expect in the coming years. She has established her own research program to develop drugs that block the detrimental effects of apoE4 on nerve cells in collaboration with Dr. Robert W. Mahley at the Gladstone Institute.

China will deploy a modern vocational education program to improve the quality of the country's vast labor force and increase employment. The State Council, China's cabinet, says this program is a strategic move for the country's economic transformation and improvement of people's wellbeing. The Chinese government has advocated a contemporary vocational education that helps nurture tens of millions of engineers and technical workers, and 'open a gate of success for young people'. A recent statement from the State Council says China will also enhance market competitiveness of products made in China to help upgrade the Chinese economy. New measures to strengthen vocational education include giving vocational schools more decision-making power. A talent cultivation mechanism will be set up to allow schools and enterprises to jointly recruit and train talents. China's food and drug safety watchdog has revoked licenses of around 70 drug businesses in a crackdown on illegal drug-related operations since last July. China Food and Drug Administration says almost 500 cases involving illegal or criminal practices were handed over to police authorities during the crackdown. The administration has ordered some 1,000 drug producers and dealers to suspend business and has withdrawn over 250 good practice certificates. In July last year, the administration launched a six-month crackdown on illegal drug-related production and operations. The campaign especially targeted at violations in the traditional Chinese medicine market and online drug sales. It is also aimed at establishing more regulations and mechanisms to intensify management, and better control drug safety risks. In a related development, China's Food and Drug Administration has launched a trial program in which food producers will have their own chief safety officers. A chief safety officer will be appointed by the owner of a food producer. The officer will be responsible for all issues regarding the safety of food produced by the company. The Food and Drug Administration hopes this will solve the problem in which everyone in the management is responsible for food safety, but actually, no one is doing the job. Meanwhile, the whole process from production to sales will be recorded and be made traceable. The growing number of cell phone users in China has led to a surge in data flow as more of them access mobile Internet via their phones. A latest government data shows the number of cell phone users in China hit 1.2 billion in January, up over 6 million from December last year. China's Ministry of Industry and Information Technology says the increase has boosted mobile Internet traffic, which reached 133 million gigabytes in January, up almost 50 percent year on year. Business revenues of mobile telecommunications hit almost 70 billion yuan, or about 11 billion U.S. dollars in January, up 11 percent year on year. Exciting research suggests that a shot every one to three months may someday give an alternative to the daily pills that some people take now to cut their risk of getting HIV. The experimental drug has only been tested in monkeys, but it completely protected them from infection. A US AIDS expert hails the move as the most exciting innovation in the field of HIV prevention. Dr. Robert Grant is an AIDS expert at the Gladstone Institutes, a foundation affiliated with the University of California in San Francisco. He says the study has showed 100 percent protection. The doctor says if the drug works and proves to be safe, it would allow for HIV to be prevented with periodic injections, perhaps every three months. You're listening to NEWS Plus Special English. I'm Yun Feng in Beijing. You can access our program by logging onto NEWSPlusRadio.cn. If you have any comments or suggestions, please let us know by e-mailing us at mansuyingyu@cri.com.cn. That's mansuyingyu@cri.com.cn. Now the news continues. The World Health Organization calls Dengue fever one of the greatest threats to global health. The WHO says a hundred million new cases are reported each year, mainly in urban areas of the tropics. Despite attempts to control mosquitoes that spread the disease, the number of cases in Malaysia has witnessed a serious spike already this year. Municipal crews swoop into action after several reports of dengue fever in a Kuala Lumpur suburb. To combat the disease, conventional methods like inspections, fogging and public education remain crucial. Health officials are calling for concerted efforts against mosquitoes to turn the tide against this 21st century plague. A new study in Finland shows healthy diet in midlife decreases risk of memory disorder in old age. This healthy diet contains abundant vegetables, fruits, berries and fish. Meanwhile, an unhealthy diet with a lot of saturated fatty acid significantly increases risks of dementia and Alzheimer's disease. Scientists in the University of Eastern Finland randomly selected a total of 2,000 people aged 50 during the years between 1972 and 1987. Their diet information was obtained through questionnaires and interviews. Re-examination was conducted in 1998 to check the health conditions of 1,500 survivors aged 65 to 79. Compared with the group of people whose diet was the least healthy, those who ate the healthiest food had their risks of dementia and Alzheimer's disease reduced by around 90 percent. The study also shows that a diet with abundant unsaturated fatty acid, Vitamin C, Vitamin B12 and folic acid helps enhance memory. Additionally, the study shows that coffee can prevent memory disorder in old age. People who drank 3 to 5 cups of coffee per day at midlife had less risks of suffering from dementia in old age than those who drank less than 3 cups of coffee per day.

Eva LaDow is a post-doctoral fellow at the Gladstone Institutes of Neurological Disease. Her project at Gladstone aims to determine whether any drugs already approved by the FDA may also be used to treat ALS, or Lou Gehrig’s disease. She grows neurons, introduces mutant DNA into the neurons to mimic ALS, and then collects and analyzes the data. LaDow says her job is “full of cool things!” The “coolest” is working with the third generation of the lab’s automated microscope, the Brain Bot. The microscope allows her to take pictures each day of tens of thousands of individual neurons and keep track of them for weeks or months. LaDow also enjoys sharing the work she is doing with local high school students through special events like “Brain Awareness Week” and teaching at the Community College of San Francisco.

An epigeneticist studies how the heart is formed

A cardiologist studies stem cells and heart development

MONDAY, MAY 21 - 2012, 3:30 pm PST/6:30 pm EST Steven Finkbeiner, MD, PhD  Director, Taube-Koret Center for Huntington's Disease Research Senior Investigator and Associate Director, Gladstone Institute of neurological Disease Professor of Neurology and Physiology, University of California, San Francisco Areas of Investigation Research in his laboratory focuses on molecular mechanisms of plasticity and neurodegeneration. A long- term goal of his research is to understand how neuronal activity elicits changes in gene expression that are important for learning and memory and aims to understand how an inherited genetic mutation leads to neuronal dysfunction and degeneration in Huntington's disease (HD). Dr. Finkbeiner will be with us to give us his research updates. Ongoing Studies C-terminus of the NMDA receptor couple Ca2+influx Gene targets of the NMDA receptor Subsynaptic protein translation in learning and memory Polyglutamine expansion degeneration in neurons Ubiquitination and proteasome function in      neurodegeneration Normal function of huntingtin Predictors of neurodegeneration  

This half-hour program looks at heart disease – the number one killer in the United States – from the point of view of a teenager trying to lower her risk, a heart attack survivor, and a scientist working to rebuild damaged hearts.

Scientists in San Francisco have coaxed mouse hearts to repair themselves from within. The breakthrough could lead to treatments for the 5 million people in the United States living with a damaged heart.

Scientists in San Francisco have coaxed mouse hearts to repair themselves from within. The breakthrough could lead to treatments for the 5 million people in the United States living with a damaged heart.

Monday, April 16, 2012 at 3:30 pm PST/6:30 pm EST Dr. Paul Muchowsli is Associate Investigator at Gladstone Institute of Neurological Disease and Associate Professor of Neurology at UCSF in California. The major research goal of his lab is to understand the molecular mechanisims that underlie neurodegenerative disorders associated with protein musfolding and aggregation, focusing on Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). The long-term goal is to use information gained from mechanism-based approaches to identify novel therapeutic targets for small molecules that could prevent neurodegeneration in humans. This is going to be a very interesting and challenging episode.

The Way of the Warrior. DS9 promised a new kind of Star Trek from the very start, yet the early seasons had more in common with the TNG method of storytelling than the rich and intricate Deep Space Nine we came to love. Just as TNG grew the beard with “The Best of Both Worlds,” so did DS9 with “The Way of the Warrior.” Shaving the head set DS9 on a course for greatness and its place as the most unique series in the Star Trek franchise. In this episode of The Ready Room we discuss “The Way of the Warrior” and how it changed Deep Space Nine. In news we look at the official music video for William Shatner's cover of “Bohemian Rhapsody,” Five Year Missions “Errand of Mercy,” a comparison of Star Trek technology to real-world progress, Microsoft's progress in holodeck technology, John de Lancie reading “The Raven,” and the Roddenberry Foundation's $5 million dollar gift to the Gladstone Institutes for stem cell research. 

Monday, August 29, 2011 at 3:30 pm PT/6:30 pm ET/11:30 pm UK time– Our incredible special guest tonight is Diana Dunkelberger from the Paul Muchowski Lab at the Gladstone Institute, UC San Francisco in California. She recently received the HDSA Donald A. King Student Fellowship which gave her the financial resources to dedicate her summer to HD research. Diana aspires to become a Neurologist and conduct translational research, so she will be heading off to medical school in the fall. We are going to learn about her very special project: Investigating the Immune System and the Role of the Cannabinoid Receptor (Type-2) in the Pathogenesis of Huntington's Disease. Diana will present comprehensive scientific information about her research. She is passionate about her work and says the main point to illustrate is that science isn't big and scary,so this will definitely be a very educational and interesting episode.

Katherine Pollard, Associate Investigator at the Gladstone Institutes and Associate Professor of Biostatistics at UC San Francisco, specializes in evolutionary genomics, in particular identifying genome sequences that differ significantly between or within species and their relationship to biomedical traits. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21984]

Katherine Pollard, Associate Investigator at the Gladstone Institutes and Associate Professor of Biostatistics at UC San Francisco, specializes in evolutionary genomics, in particular identifying genome sequences that differ significantly between or within species and their relationship to biomedical traits. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21984]

Robert M. Grant of the Gladstone Institute of Virology & Immunology, Susan Chambré, author of “Fighting for Our Lives: New York’s AIDS Community and the Politics of Disease," and Elaine Abrams of Columbia's Mailman School of Public Health.

Are humans unique or do we just do some things a little better than other species? In the second of our two-part series – how our ability to adapt has shaped our evolution. Find out how throwing a burger on the grill has transformed our species… the 1% genetic difference that separate us from chimps… why we're poorly adapted and stressed out … and why human evolution is not only on the move, but picking up the pace. Richard Wrangham - Biological anthropologist at Harvard University and author of Catching Fire: How Cooking Made Us Human Katherine Pollard - Biostatistician at the Gladstone Institutes at the University of California, San Francisco Robert Sapolsky - Biological scientist at Stanford University and neurologist at Stanford's School of Medicine. Author of Why Zebras Don't Get Ulcers, Third Edition and, more recently, Monkeyluv: And Other Essays on Our Lives as Animals Gregory Cochran - Anthropologist at the University of Utah and co-author of The 10,000 Year Explosion: How Civilization Accelerated Human Evolution Descripción en español Learn more about your ad choices. Visit megaphone.fm/adchoices

ENCORE Are humans unique or do we just do some things a little better than other species? In the second of our two-part series – how our ability to adapt has shaped our evolution. Find out how throwing a burger on the grill has transformed our species… the 1% genetic difference that separate us from chimps… why we’re poorly adapted and stressed out … and why human evolution is not only on the move, but picking up the pace. Richard Wrangham - Biological anthropologist at Harvard University and author of Catching Fire: How Cooking Made Us Human Katherine Pollard - Biostatistician at the Gladstone Institutes at the University of California, San Francisco Robert Sapolsky - Biological scientist at Stanford University and neurologist at Stanford’s School of Medicine. Author of Why Zebras Don't Get Ulcers, Third Edition and, more recently, Monkeyluv: And Other Essays on Our Lives as Animals Gregory Cochran - Anthropologist at the University of Utah and co-author of The 10,000 Year Explosion: How Civilization Accelerated Human Evolution Descripción en español

A neuroscientist digs deep into the genetics of Huntington's Disease

In this episode, Dr. Bob Grant, Associate Professor of Medicine at UCSF and an investigator at the Gladstone Institute of Virology and Immunology, discusses the PrEP Initiative study. These trials are trying to determine whether HIV medications given to HIV negative people at higher risk of infection will help reduce the amount new infections. Get the Flash Player to listen to our podcast in your browser. Dr. Grant will be a speaker at our HIVision forum in San Francisco on...