Podcasts about ipscs

In this episode of the Epigenetics Podcast, we talked with Boyan Bonev from the HelmholtzZetrum in Munich about his work on neuroepigenetics, focusing on gene regulation, chromatin architecture, and primate epigenome evolution, This Episode focuses on Dr. Bonev's recent research, particularly focusing on how chromatin architecture and gene regulation influence neural cell identity and function. He discusses his work investigating transcriptional activity in relation to chromatin insulation, highlighting a critical finding that induced expression of genes does not necessarily lead to chromatin insulation—a point that complicates prior assumptions about the relationship between gene expression and chromatin organization. This study aimed to determine the causal versus correlative aspects of chromatin architecture in brain development and links it to developmental processes and neurodevelopmental disorders. Building on his findings in gene regulation, Dr. Bonev elaborates on a significant study he conducted in his own lab, where he mapped the regulatory landscape of neural differentiation in the mouse neocortex. Here, he employed cutting-edge single-cell sequencing methodologies to analyze intricate gene and enhancer interactions, revealing that selective enhancer-promoter interactions are primarily cell-type specific. This nuanced understanding aids in deciphering the complexities associated with gene expression as it relates to neural stem cells and differentiated neurons, emphasizing the importance of single-cell analyses over bulk sequencing methods. Moreover, Dr. Bonev reveals a novel methodology developed in his lab that allows for the simultaneous assessment of spatial genome organization, chromatin accessibility, and DNA methylation at high resolution. This advancement not only reduces costs but also enhances the potential to correlate higher-dimensional genomic data with specific biological questions, fostering a more integrative approach to understanding genetic regulation. The discussion then shifts focus towards Dr. Bonev's recent project profiling primate epigenome evolution, where he investigated the 3D genome organization, chromatin accessibility, and gene expression among iPSCs and neural stem cells from various species, including humans, chimpanzees, gorillas, and macaques. In this research, he identifies trends related to transcription factor evolution and chromatin modifications across species. The insights gleaned from this work underscore the evolutionary significance of structural variations in the 3D genome, pointing to a possible link between chromatin dynamics and the evolutionary development of the primate brain.   References Bonev B, Mendelson Cohen N, Szabo Q, Fritsch L, Papadopoulos GL, Lubling Y, Xu X, Lv X, Hugnot JP, Tanay A, Cavalli G. Multiscale 3D Genome Rewiring during Mouse Neural Development. Cell. 2017 Oct 19;171(3):557-572.e24. doi: https://doi.org/10.1016/j.cell.2017.09.043. PMID: 29053968; PMCID: PMC5651218. Noack, F., Vangelisti, S., Raffl, G. et al. Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler. Nat Neurosci 25, 154–167 (2022). https://doi.org/10.1038/s41593-021-01002-4 Noack F, Vangelisti S, Ditzer N, Chong F, Albert M, Bonev B. Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids. Nat Cell Biol. 2023 Dec;25(12):1873-1883. doi: 10.1038/s41556-023-01296-5. Epub 2023 Nov 23. PMID: 37996647; PMCID: PMC10709149.   Related Episodes Characterization of Epigenetic States in the Oligodendrocyte Lineage (Gonçalo Castelo-Branco) Polycomb Proteins, Gene Regulation, and Genome Organization in Drosophila (Giacomo Cavalli) The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Tired of treating symptoms?Dive into the future of medicine with Dr. Panos Chrysanthopoulos (CDO at Morphocell Technologies and co-founder and director of weCANdev Consulting Group Inc. in Canada)! Discover how iPSCs create personalized CAR-T cell therapies for chronic liver failure and explore the potential to phase out diseases like leukemia within the next 5-10 years.Join us as we explore:CRISPR-Cas9: The DNA scissors rewriting the rules of medicine.iPSCs (Induced Pluripotent Stem Cells): The key to personalized, regenerative therapies.CAR-T Cell Therapy: Tailored immune responses to fight cancer.Quality by Design (QbD): Guaranteeing the safety and efficacy of next-gen treatments.Ethical considerations and equitable access: Navigating the future of gene editing responsibly.Don't forget to leave us a review and follow us on Spotify, LinkedIn, X, TikTok, and YouTube (Giota Pimenidou). Visit our website at www.global-greek-influence.com for more engaging content!

We've spent the better part of the last two decades unravelling exactly how the human genome works and which specific letter changes in our DNA affect things like diabetes risk or college graduation rates. Our knowledge has advanced to the point where, if we had a safe and reliable means of modifying genes in embryos, we could literally create superbabies. Children that would live multiple decades longer than their non-engineered peers, have the raw intellectual horsepower to do Nobel prize worthy scientific research, and very rarely suffer from depression or other mental health disorders.The scientific establishment, however, seems to not have gotten the memo. If you suggest we engineer the genes of future generations to make their lives better, they will often make some frightened noises, mention “ethical issues” without ever clarifying what they mean, or abruptly change the subject. It's as if humanity invented electricity and decided [...] ---Outline:(02:17) How to make (slightly) superbabies(05:08) How to do better than embryo selection(08:52) Maximum human life expectancy(12:01) Is everything a tradeoff?(20:01) How to make an edited embryo(23:23) Sergiy Velychko and the story of super-SOX(24:51) Iterated CRISPR(26:27) Sergiy Velychko and the story of Super-SOX(28:48) What is going on?(32:06) Super-SOX(33:24) Mice from stem cells(35:05) Why does super-SOX matter?(36:37) How do we do this in humans?(38:18) What if super-SOX doesn't work?(38:51) Eggs from Stem Cells(39:31) Fluorescence-guided sperm selection(42:11) Embryo cloning(42:39) What if none of that works?(44:26) What about legal issues?(46:26) How we make this happen(50:18) Ahh yes, but what about AI?(50:54) There is currently no backup plan if we can't solve alignment(55:09) Team Human(57:53) Appendix(57:56) iPSCs were named after the iPod(58:11) On autoimmune risk variants and plagues(59:28) Two simples strategies for minimizing autoimmune risk and pandemic vulnerability(01:00:29) I don't want someone else's genes in my child(01:01:08) Could I use this technology to make a genetically enhanced clone of myself?(01:01:36) Why does super-SOX work?(01:06:14) How was the IQ grain graph generated?The original text contained 19 images which were described by AI. --- First published: February 19th, 2025 Source: https://www.lesswrong.com/posts/DfrSZaf3JC8vJdbZL/how-to-make-superbabies --- Narrated by TYPE III AUDIO. ---Images from the article:

In this episode, Hitomi provides an overview of where we are and why on our roadmap to treatments and a cure, shared at last weekend's Project CASK Open House!Hear about:

In this podcast, we spoke with Dr. Jorge Escobar Ivirico, Product Manager, Bioprocess Solutions at Eppendorf, about the fascinating world of induced pluripotent stem cells (iPSCs), exploring their groundbreaking potential in regenerative medicine, personalized therapies, and drug development. Our guest explained how iPSCs, created by reprogramming adult somatic cells, can differentiate into virtually any cell type, making them invaluable for research and therapeutic applications. We delved into the importance of consistency, quality control, and reproducibility in iPSC production, alongside the challenges of culturing these cells, such as maintaining pluripotency and scaling production for clinical use. The discussion highlighted exciting advancements, including the development of organoids and universal T cells, as well as the ethical considerations distinguishing iPSCs from embryonic stem cells. Looking to the future, Jorge envisioned iPSCs becoming a cornerstone of standard medical practice, while acknowledging the need to address safety, scalability, and regulatory hurdles to fully realize their potential. What are Induced Pluripotent Stem Cells (iPSCs)? "Induced pluripotent stem cells are a type of stem cell created by reprogramming adult somatic cells, like skin or blood cells, back into an embryonic-like state," explains Jorge. This process involves introducing specific transcription factors, often called Yamanaka factors, to transform these cells into a versatile state. Once reprogrammed, iPSCs can differentiate into almost any cell type, making them invaluable tools for research, drug development, and potentially life-changing therapies. The Growing Importance of iPSCs iPSCs offer a range of advantages, particularly their ability to sidestep ethical concerns tied to embryonic stem cell use. “What makes iPSCs so important today,” Jorge notes, “is their versatility and potential applications. Researchers can create patient-specific cell lines, which are essential for drug screening, disease modeling, and personalized medicine.” This technology is pivotal for regenerative medicine, offering hope for repairing damaged tissues and organs. “From neurodegenerative diseases to heart damage, iPSCs open the door to innovative treatment possibilities,” he adds. Mastering the Production Process Producing iPSCs is a meticulous endeavor. "Consistency is key," emphasizes Jorge. Researchers must ensure that each batch of cells meets strict criteria to avoid unpredictable outcomes, especially when precision is vital in both research and therapeutic applications. Standardized protocols and quality control measures are essential to achieve consistency. These involve monitoring for contamination and verifying the cells' ability to differentiate into various cell types. “Imagine developing a therapy based on a specific batch of cells, only to find that subsequent batches behave differently,” he warns. “Such inconsistencies can jeopardize patient outcomes.” Tackling Challenges in Culturing iPSCs Culturing iPSCs presents its own set of challenges. High cell numbers are often needed for large-scale research or therapeutic applications, but scaling up production without compromising quality is no small feat. Maintaining the cells' pluripotent state is another hurdle, as they can easily differentiate prematurely under certain culture conditions. "Environmental parameters like temperature, pH, oxygen levels, and nutrient availability must be rigorously controlled," Jorge explains. “Even minor fluctuations can negatively impact cell health and their ability to remain pluripotent.” Innovations Addressing Culturing Hurdles To overcome these challenges, researchers are turning to advanced techniques like 3D culture systems and bioreactors. These provide a more natural growth environment for the cells, enhancing their viability and functionality. “By transitioning from traditional 2D cultures to 3D systems,

Dr. Marius Wernig is a Professor of Pathology and a Co-Director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University, where his research interests include direct reprogramming and neurological disease modeling. He talks about his early work reprogramming neuronal cells from fibroblasts, adopting iPSCs, and growing his lab. He also discusses his recent research on cell therapy for brain and skin diseases, as well as his musical talents outside of the lab.

Send us a textIn the second part of our conversation with Andrea Gough, Senior Director for Advanced Instruments' Solentim Portfolio, we'll explore how AI and machine learning have, in recent years, begun to transform various aspects of biotechnology, including cell line development (CLD). Andrea shares insights into how these cutting-edge technologies are being applied to the early stages of clone selection.AI's capability to analyze images and classify clone viability is another breakthrough. Feeding thousands of images into AI systems allows for efficient and accurate decision-making, reducing the workload on scientists.Here are three key takeaways from our conversation:Leverage AI and Machine Learning: Integrate AI to streamline clone selection and optimize cell line development processes. AI can identify key phenotypic identifiers and predict the best clones, driving efficiency and productivity.Diversify Expression Systems: While CHO cells dominate the protein therapy space, exploring alternative systems like HEK cells, MSCs, IPSCs, and even insect cells can offer unique benefits and improve gene therapy productions.Maintain Comprehensive Documentation: Ensure rigorous tracking and documentation of all processes. From certificates of analysis to raw image data, having meticulous records will safeguard your development process and aid compliance with regulatory standards.Tune in to the full episode for more insights on overcoming challenges in cell line development and tips for setting up successful bioprocessing workflows!Connect with Andrea GoughLinkedIn: www.linkedin.com/in/andrea-gough-72915282Advanced Instruments: www.aicompanies.comNext Steps:Wondering how to develop cell and gene therapies with peace of mind? Schedule your free assessment to propel your success: https://bruehlmann-consulting.com/assessmentDevelop biologics better, faster, at a fraction of the cost with our Fractional CTO services. Curious? DM us at hello@bruehlmann-consulting.com

Markus Gstöttner is the CEO of Clock.bio, a company devoted to extending and improving the quality of life by reversing the harmful effects of time in our cells. With an unusual background spanning public service and cultured meat entrepreneurship, Gstöttner brings a fresh perspective to longevity biotechnology. In this episode, Gstöttner shares how his company is working to extend healthspan by understanding and harnessing the natural rejuvenation capabilities of stem cells. The conversation explores Clock.bio's groundbreaking approach to identifying the genes and pathways involved in cellular rejuvenation, and their vision for translating these discoveries into therapies.The Finer Details:How induced pluripotent stem cells (iPSCs) naturally resist and reverse agingClock.bio's novel platform for forcing stem cells to age and studying their spontaneous rejuvenationThe company's comprehensive genetic screen identifying over 150 rejuvenation-related genes, the Atlas of Rejuvenation FactorsStrategies for validating these discoveries and developing therapeutic applicationsThe path from discovery to clinical trials for extending human healthspan

In this podcast, we spoke with Ryan Bernhardt, CEO of Biosero and Jesse Mulcahy, Director and Head of Automation at Cellino about the importance of utilizing automation in cell therapy research and production and the potential of these technologies to transform the healthcare landscape and improve patient access. The Challenge of Accessibility in Cellular Therapy The traditional methods of creating induced pluripotent stem cells (iPSCs) are notoriously laborious and expensive, often costing hundreds of thousands, if not millions, of dollars per patient. This high cost poses a substantial barrier to accessibility for many patients in need of personalized cell therapy treatments. Cellino is leveraging advanced automation, AI, and linear technology to dramatically redefine and improve on traditional production processes. Advancing Automation in Cell Therapy Cellino's approach employs its innovative technology, known as NEBULA. This system utilizes self-contained units, referred to as cassettes, to cultivate personalized cell therapies directly in hospitals. NEBULA uses AI to monitor cell growth while incorporating laser technology to selectively eliminate unhealthy cells. This level of automation has the potential to reduce the manufacturing costs of personalized stem cell therapies by at least tenfold, making treatments more accessible to a broader range of patients. Supporting automation for Cellino is Biosero's Green Button Go software suite, which plays a crucial role in automating the workflows of life science organizations. Ryan explained how their technology empowers life science organizations to automate essential scientific processes, facilitating the scheduling of workflows and direct communication with lab instruments. With the capability to run processes continuously—day or night—labs can maintain and cultivate cells without the constraints of a conventional workweek. This 24/7 operational capacity allows for the rigorous demands of cellular therapeutics to be met more efficiently. Bridging Gaps with Integrated Automation Ryan describes how lab automation can no longer be seen as merely robotic arms and conveyor belts; it integrates three key elements: physical, logical, and data. By orchestrating these components, automation streamlines and accelerates research across labs that were traditionally siloed and specialized in specific areas. This approach connects different labs, unifying knowledge, expertise, and data systems, enabling real-time decision-making and data-driven insights. Automation enhances workflows by eliminating delays and optimizing project timelines. It serves as a performance tool for scientists, improving efficiency, consistency, and the ability to address complex challenges, while also incorporating AI and machine learning for smarter, continuous processes. Jesse Mulcahy, Director and Head of Automation at Cellino emphasized the significance of Biosero's orchestration software in improving efficiency by optimizing scheduling, reducing downtime, and maximizing throughput in cell therapy production. The Green Button Go orchestrator improves consistency by automating key steps and minimizing human intervention, ensuring reproducible results for quality control. The software is flexible and modular, allowing for easy adaptation of workflows as needs evolve, whether adding new instruments or changing protocols. This scalability is crucial for producing personalized cell therapies more efficiently and at a larger scale. Addressing Pain Points and Future Trends Despite the advancements, there are still hurdles to overcome in the biologics' development landscape. Ryan notes that the field is evolving rapidly, with significant advancements in cell culturing, automation, and decision-making processes. Traditional cell culturing is being automated to assess key factors like cell viability, confluence, and other qualitative aspects, aiding decisions on feeding, splitting, and harvesting.

In this Dementia Researcher Podcast episode, Dr Aitana Sogorb Esteve hosts a discussion with Dr Charlie Arber and Sam Crawford from University College London, discussing their work on familial British dementia (FBD), a rare form of dementia affecting only a handful of families. The discussion explores the latest findings from human stem cell models that are helping researchers understand FBD's unique genetic and pathological features, and how that can inform a wider understanding of familial Alzheimer's Disease. Topics covered include: - Genetic causes and symptoms of familial British dementia - Use of stem cell models, particularly iPSCs, to study FBD in the lab - Potential biomarkers and implications for therapeutic research - How funding from the Race Against Dementia Ignition Fund is supporting advancements in rare dementia research -- Full biographies on all our guests and a transcript can be found on our website: https://www.dementiaresearcher.nihr.ac.uk Find out more at Race Against Dementia: https://www.raceagainstdementia.com/ -- Like what you see? Please review, like, and share our podcast - and don't forget to subscribe to ensure you never miss an episode . -- This podcast is brought to you by University College London / UCLH NIHR Biomedical Research Centre in association with Alzheimer's Association, Alzheimer's Research UK, Alzheimer's Society and Race Against Dementia who we thank for their ongoing support. -- Follow us on social media: http://www.instagram.com/dementia_researcher/ http://www.facebook.com/Dementia.Researcher/ http://www.twitter.com/demrescommunity http://www.linkedin.com/company/dementia-researcher http://bsky.app/profile/dementiaresearcher.bsky.social -- Download our new community app: https://onelink.to/dementiaresearcher

In the future, doctors will be able to create tiny replicas of your tissues in the lab, and then test them against a range of drugs, revealing exactly which treatments would work best for you before you even visit a drug store. This future of personalised medicine is driven by researchers such as Dr. Robert Kass of the Columbia University Medical Center. Kass and colleagues have pioneered the use of stem cells to develop personalized treatments for a genetic heart condition that disrupts normal heart rhythms. The researchers reprogrammed a patient's skin cells into stem cells called induced pluripotent stem cells (or iPSCs for short), and they then induced the iPSCs to turn into heart cells. This allowed the research team to study how genetic mutations in the resulting heart cells affect the heart's ion channels. Their research revealed that a mutation in a specific sodium channel was causing dangerous heart rhythms and that combining the drug mexiletine with a pacemaker device to increase heart rate, provided an effective and personalised treatment.

In this episode of the Epigenetics Podcast, we talked with Mitinori Saitou from Kyoto University about his work on germ cell development, focusing on proteins like BLIMP1 and PRDM14, reprogramming iPSCs, and his vision to address infertility and genetic disorders through epigenetic insights. To start our discussion, Dr. Saitou shares the foundation of his research, which centers on the mechanisms of germ cell development across various species, including mice, non-human primates, and humans. He provides insight into his early work examining the roles of two key proteins: BLIMP1 and PRDM14. These proteins are essential for germline specification in mammals, and their functions are unveiled through detailed exploration of knockout models. In particular, Dr. Saitou elucidates the critical events in germ cell specification, highlighting how disruptions to the functions of these proteins lead to significant impairments in development. As the conversation deepens, we discuss Dr. Saitou's groundbreaking advances in human-induced pluripotent stem cells (iPSCs). He elaborates on the processes involved in reprogramming these cells to form primordial germ cell-like cells, emphasizing the significance of understanding various cellular contexts and transcriptional regulation. Dr. Saitou then details how overexpression of certain factors in embryonic stem cells can induce these germline characteristics, presenting the promise of innovation in regenerative medicine and reproductive biology. We end our talk with the exploration of chromatin remodeling that occurs during germ cell development, including fascinating details about DNA and histone modification dynamics. Dr. Saitou articulates how the epigenetic landscape shifts during the transition from pluripotent states to germ cell specification, providing a detailed comparison between mouse and human systems. This highlights the complexity of gene regulation and the importance of specific epigenetic markers in establishing and maintaining cellular identity.   References Yamaji, M., Seki, Y., Kurimoto, K. et al. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 40, 1016–1022 (2008). https://doi.org/10.1038/ng.186 Katsuhiko Hayashi et al., Offspring from Oocytes Derived from in Vitro Primordial Germ Cell–like Cells in Mice. Science 338, 971-975 (2012). DOI: 10.1126/science.1226889 Nakaki, F., Hayashi, K., Ohta, H. et al. Induction of mouse germ-cell fate by transcription factors in vitro. Nature 501, 222–226 (2013). https://doi.org/10.1038/nature12417 Nakamura, T., Okamoto, I., Sasaki, K. et al. A developmental coordinate of pluripotency among mice, monkeys and humans. Nature 537, 57–62 (2016). https://doi.org/10.1038/nature19096 Murase, Y., Yokogawa, R., Yabuta, Y. et al. In vitro reconstitution of epigenetic reprogramming in the human germ line. Nature 631, 170–178 (2024). https://doi.org/10.1038/s41586-024-07526-6   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

Unlocking the Secrets of the Six-Base GenomeEpigenetics was somewhat vague when I was an undergraduate ( a long time ago). So I was curious to get an update on how we can investigate it more closely and what we are learning. I talked to Tom Charlesworth, Director of Market Strategy and Corporate Development at biomodal, a sequencing technology company focused on epigenetics. Tom explained how modifications beyond the traditional four DNA bases impact gene expression, development, and disease. What is the Six-Base Genome?Tom introduced biomodal as a sequencing technology company spun out of the University of Cambridge, focused on the interface between genetics and epigenetics. Their technology goes beyond the traditional four-base genome (A, T, G, and C) by adding two epigenetically modified bases: methylcytosine (5-MC) and hydroxymethylcytosine (5-HMC). This “six-base” approach captures critical modifications that play distinct roles in gene regulation.5-MC is associated with repressing gene expression, often keeping certain genes “turned off,” while 5-HMC is linked to opening chromatin and activating gene expression. Understanding these modifications provides a more dynamic picture of how our genes are regulated—not just by the sequence of DNA but also by chemical marks that change over time.Bridging the Gap Between Genetics and FunctionThe traditional four-base genome gives us an invaluable map of our genetic code, but it falls short of explaining how the same genetic sequence could lead to such diverse outcomes—from development to disease. Epigenetic modifications, like 5-MC and 5-HMC, offer another layer of regulation that's essential for gene expression. Tom highlighted research that illustrates the value of this additional information. He mentioned the work of developmental biologist Emily Hodges, who uses the six-base data to study chromatin accessibility during neuronal stem cell differentiation. Emily found that early changes in 5-HMC could predict chromatin opening, an insight that would be invisible if one only looked at 5-MC. This kind of nuanced view helps us understand the precise moments when genes are primed for activation, offering a clearer picture of developmental biology.Applications From Oncology to NeurologyTom described three main areas where their customers are leveraging the six-base genome: fundamental research, oncology, and neurology.In oncology, there's a growing recognition that multi-omic data—integrating genetic and epigenetic information—can improve cancer detection and treatment response. Tom shared examples of ongoing projects in Canada and Australia, where researchers are using six-base sequencing to better understand the complex dynamics of tumor evolution. By distinguishing between 5-MC and 5-HMC in circulating tumor DNA, they hope to pinpoint which DNA fragments originate from cancer cells, providing a more accurate snapshot of the disease's state and progression.The six-base genome also shows promise in neurology. Tom explained that the brain is unique because it has an unusually high level of 5-HMC compared to other tissues, yet we still don't fully understand why. Early research is exploring this epigenetic landscape to uncover new biomarkers for diseases like Parkinson's, Alzheimer's, and various brain tumors. The ability to profile these epigenetic marks could lead to breakthroughs in diagnosing and potentially treating neurological disorders.Are you subscribed yet? If not, let's fix that.Epigenetics as a “Life Record”: The Developmental and Environmental ContextHere's another way think about the six-base genome—as a record of a cell's developmental journey and its responses to the environment. During early development, epigenetic marks guide cells down specific paths, setting up the blueprint for tissues and organs. But later in life, these marks are influenced by external factors like diet, aging, and environmental exposures. This can lead to changes in gene expression that contribute to disease, aging, or even resilience against external stressors.We also touched on how this concept applies to reprogramming cells, such as in induced pluripotent stem cells (IPSCs). When cells are reprogrammed, they don't just revert to a blank slate; their epigenetic history still influences how they behave. Tom described work showing that successful reprogramming often involves restoring specific epigenetic marks, essentially rewinding the “epigenetic clock” to a more youthful state.Rethinking DNA as the Sole BlueprintTraditionally, DNA has been viewed as the ultimate blueprint for life. But the static genome represents only a portion of the story—it's the interaction with the adaptable epigenome that truly dictates how our genetic potential is realized. The six-base genome isn't just a scientific curiosity; it's another tool for decoding the complexities of life.Tom describes DNA as the “possibility space” of an organism, but it's the epigenetic modifications that trim and shape this space into the reality we observe. This nuanced view challenges us to look beyond the sequence and consider the rich layers of regulation that determine who we are and how we function.I am most excited to learn how environmental conditions like diet and maybe even experience influence the epigenome. As a bacterial geneticist, my basic model is substance A interacts with some regulatory protein to turn a gene on or off. I want to know how the epigenome records my environment. Do the conversations I have had leave detectable marks on the chromosomes in my brain? What would be the mechanism for that? Regardless of the outcome, it's fun to see the ever increasing depth of our understanding of biology.Your deepest insights are your best branding. I'd love to help you share them. Chat with me about custom content for your life science brand. Or visit my website.If you appreciate this content, you likely know someone else who will appreciate it too. Please share it with them. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

In this insightful episode of Research Renaissance, host Deborah Westphal engages in an enlightening conversation with Dr. Zhe Zhang, a research associate at Johns Hopkins and a 2021 Toffler Scholar. Dr. Zhang discusses her journey from aspiring to be a doctor to becoming a dedicated researcher focused on neurodegenerative diseases, particularly ALS. She shares her innovative work on establishing a platform to find genetic modifiers that can improve cell survival and slow the progression of ALS.Key Discussion Points:Introduction to Dr. Zhe Zhang:Background and inspiration for pursuing research in neurodegenerative diseases.Transition from clinical practice to basic research.Journey to ALS Research:Initial interest sparked by experiences with neurodegenerative patients during medical training.Shift in focus during her time in Australia, influenced by collaborations and the Ice Bucket Challenge.Focus on Genetic Modifiers and ALS:Explanation of familial and sporadic ALS, with a focus on the C9ORF72 gene mutation.Development of toxic proteins from gene mutations and their impact on cell survival.Research Techniques and Platforms:Use of CRISPR technology for genetic screening and identifying potential therapeutic targets.Application of human induced pluripotent stem cells (iPSCs) to develop models for screening.Collaborative Efforts:Importance of interdisciplinary collaborations with other researchers and biobanks.Contributions from patient-donated post-mortem tissues to validate research findings.Challenges and Future Directions:The complexity of translating basic research to clinical applications and commercial products.The role of CRISPR in gene editing and its potential for therapeutic interventions.Emerging Technologies and Tools:The impact of iPSCs, CRISPR, and advanced imaging techniques on ALS research.Potential of functional MRI and other non-invasive methods for tracking disease progression.Global Collaboration and Impact:The necessity of global studies and collaborations to understand neurodegenerative diseases.Hopes for future research, including the development of effective therapies for ALS.Personal Reflections and Advice:Dr. Zhang's commitment to staying curious, passionate, and cautious in her research.Encouragement for young researchers to persevere despite challenges and to collaborate widely.Join us in advancing our understanding of the brain and addressing its ailments. Until then, onward and upward!To learn more about the breakthroughs discussed in this episode and to support ongoing research, visit our website at tofflertrust.org. Technical Podcast Support by Jon Keur at Wayfare Recording Co.

Dr. Ludovic Vallier is the W3 Einstein Strategic Professor for Stem Cells in Regenerative Therapies at the Berlin Institute of Health and a Max Planck Fellow at the Max Planck Institute for Molecular Genetics. His lab uses stem cells to model embryonic development in vitro and to produce liver cells with an interest for cell therapy. He talks about modeling non-alcoholic fatty liver disease and his lab's pivot to SARS-CoV-2 research early in the pandemic. He also discusses how iPSCs could be used to regenerate the liver after injury.

Sometimes experimental results are serendipitous. Listen as Associate Editor Dr. Crystal Ripplinger (University of California, Davis) talks with authors Dr. Nikki Posnack and Devon Guerrelli (both at Children's National Hospital and The George Washington University School of Engineering and Applied Science), along with expert Dr. Silvia Marchiano (University of Washington), about the new research by Guerrelli et al. published in our Call for Papers on Excitation-Contraction Coupling, Electrophysiology, and Arrhythmias. The Posnack Lab typically investigates environmental chemicals and their impact on cardiac function using microelectrode arrays to record electrical signals from human iPS cells. When performing cardiotoxicity experiments, the authors realized that their baseline measurements varied significantly between their different studies, making it difficult to combine datasets. In doing the legwork to identify potential sources of variability and improve their own internal lab protocols, the authors focused on the reproducibility of their experimental measurements using human iPSCs. Listen as we discuss important recommendations for investigators using these cells to improve their experimental reproducibility.   Devon Guerrelli, Jenna Pressman, Shatha Salameh, and Nikki Posnack hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility Am J Physiol Heart Circ Physiol, published June 9, 2024. DOI: 10.1152/ajpheart.00631.2023

Cynata Therapeutics Ltd (ASX:CYP) CEO and managing director Dr Kilian Kelly is in the Proactive studio following the 18th annual Bioshares Biotech Summit in Perth. Cynata is an Australian stem cell and regenerative medicine company that is developing a therapeutic stem cell platform technology, Cymerus™, using discoveries made at the University of Wisconsin-Madison (UWM). UWM is a world-renowned leader in stem cell research, in particular for the work by Professor James Thomson's group, which included the first successful isolation of human embryonic stem cells in 1998 and the derivation of induced pluripotent stem cells (iPSCs) from human adult cells in 2007. Professor Igor Slukvin, a co-founder of Cynata, was also a member of the team that conducted UWM's pioneering iPSC research. The Cymerus technology has several characteristics which makes it ideal for the development of cell-based therapeutics. Most critically, the Cymerus manufacturing process ensures that cells for therapeutic use can be produced in virtually limitless quantities. This means that Cynata will not have to constantly seek out fresh stem cell donors to fuel its manufacturing demands. This has the potential to create a new standard in the emergent arena of regenerative medicine and stem cell therapeutics and provides Cynata with both a unique differentiator and an important competitive position. #ProactiveInvestors #CynataTherapeutics #ASX #CYP #Biotech #Bioshares #Summit #BiosharesBiotechSummit #StemCell #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

Dr. Sebastian Diecke is a Group Leader and Stem Cell Core Director at the Max Delbrück Center, where his research focuses on iPSCs and organoid models. He talks about the early days of iPSC research, developing organoids from endangered rhinoceros, and modeling Huntington's and other diseases.

In this intriguing episode, Dr. Joseph Mazzulli, a 2022 Toffler Scholar, dives deep into the mechanisms of protein misfolding and amyloid formation, and their links to cell death in neurodegenerative diseases such as Parkinson's and Alzheimer's. Utilizing cutting-edge induced pluripotent stem cell models, Dr. Mazzulli explores how these proteins transition from a soluble to an insoluble state, leading to disease.Key Topics Covered:Understanding Protein Misfolding: An exploration of how proteins like amyloid and tau transition to harmful states in the brain.Innovative Research Techniques: Use of induced pluripotent stem cells (iPSCs) to model neurodegenerative diseases and test potential treatments.Challenges in Neurodegenerative Research: The complexities of studying common and sporadic forms of diseases without clear genetic triggers.Potential for Personalized Medicine: How iPSC technology could revolutionize treatment approaches through personalized medicine."The potential of induced pluripotent stem cells in disease modeling opens new doors for personalized medicine, transforming our approach to neurodegenerative diseases." - Joe MazzulliStay engaged with the latest in brain science by subscribing to our podcast on your favorite streaming platform. Visit our website for more resources and to join the conversation about advancing neurological research.To learn more about the breakthroughs discussed in this episode and to support ongoing research, visit our website at tofflertrust.org. Technical Podcast Support by Jon Keur at Wayfare Recording Co.

BlueRock Therapeutics' SVP Head of Development, Dr. Ahmed Enayetallah, joins Cell & Gene: The Podcast Host, Erin Harris, to discuss the company's phase I clinical trial for Parkinson's disease, which continues to show positive trends at 18 months. They cover the important role induced pluripotent stem cells' (iPSCs) play in the trial, and they also discuss the company's investigational cell therapy, bemdaneprocel.Listen and subscribe so you never miss an episode!

Biomedical researchers have long sought ways to repair spinal cord damage with the holy grail of the pursuit being the reconstitution of lost function. In the mid 1990's with the successful culture of human embryonic stem cells, and about a decade later induced pluripotent stem cells (iPSCs), the field was energized with a potential new approach to replace the lost neurons and glia cells and restoring neural connections.  In the decades since that discovery some progress has been made, however many hurdles remain, including establishing a functional synaptic connection between the transplanted and host neurons which is crucial for motor function recovery. To boost therapeutic outcomes our guests tested an ex vivo gene therapy to promote synapse formation between the donor and host neurons by expressing the synthetic excitatory synapse organizer CPTX in hiPSCs-derived neural stem and progenitor cells. Tune in to learn what they discovered. HostMartin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory@martinperaJAXGuestsHideyuki Okano, MD, PhD Keio University, Japan, Professor in the Department of Physiology and Chairman of the Graduate School of Medicine at Keio University. Professor Okano has spent decades studying neurogenesis and is currently leading a first-of-its-kind cell therapy for spinal cord injury. He has previously served as an Associate Editor for Stem Cell Reports and is a member of the Editorial Board. He is the current President of the Japanese Society of Regenerative Medicine and Vice President of the ISSCR.   Yusuke Saijo, MD. Keio University, Japan, graduated from Kyorin University School of Medicine and following a two-year initial training period, he embarked on a clinical journey, working in the field of orthopedic surgery at Keio University, specializing in the spinal cord and spinal disorders. Dr. Yusuke currently works in the research laboratory led by Professors Okano and Masaya Nakamura, where his research focuses on ex vivo cell and gene therapy for spinal cord regeneration. Supporting ContentHuman-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury, Stem Cell ReportsAbout Stem Cell ReportsStem Cell Reports is the open access, peer-reviewed  journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.Twitter: @StemCellReportsAbout ISSCRWith nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.ISSCR StaffKeith Alm, Chief Executive OfficerYvonne Fisher, Managing Editor, Stem Cell ReportsKym Kilbourne, Director of Media and Strategic CommunicationsJack Mosher, Scientific AdvisorVoice WorkBen Snitkoff

In this episode, Katy interviews Björn Vahsen to discuss his ongoing research on Motor neurone disease using iPSCs to co-culture microglia and motor neurons.

Ajantha Abey narrates his blog written for Dementia Researcher. Explore Ajantha's insights on the revolutionary impact and challenges of using induced pluripotent stem cells (iPSCs) in dementia research. Ajantha reflects on the journey with iPSC models, highlighting the groundbreaking potential to study diseases like Alzheimer's and Parkinson's by examining human brain cells without invasive methods. The blog emphasises the transformative nature of iPSC technology, which allows for in-depth exploration into the mechanisms of dementia, yet it also brings to light the considerable effort, attention, and resources required to maintain and differentiate these cells. Through a balanced lens, Ajantha offers a concise overview of the scientific opportunities iPSCs provide against the backdrop of the technical and logistical hurdles researchers face, presenting a clear picture of iPSC technology's role in advancing dementia research. Find the original text, and narration here on our website. https://www.dementiaresearcher.nihr.ac.uk/blog-the-pros-and-cons-of-using-ipscs-in-dementia-research/ #iPSCs #StemCells #DementiaResearch -- Ajantha Abey is a PhD student in the Kavli Institute at University of Oxford. He is interested in the cellular mechanisms of Alzheimer's, Parkinson's, and other diseases of the ageing brain. Previously, having previoulsy explored neuropathology in dogs with dementia and potential stem cell replacement therapies. He now uses induced pluripotent stem cell derived neurons to try and model selective neuronal vulnerability: the phenomenon where some cells die but others remain resilient to neurodegenerative diseases. -- Enjoy listening and reading our blogs? We're always on the look out for new contributors, drop us a line and share your own research and careers advice dementiaresearcher@ucl.ac.uk This podcast is brought to you in association with Alzheimer's Association, Alzheimer's Research UK, Alzheimer's Society and Race Against Dementia, who we thank for their ongoing support. -- Follow us on Social Media: https://www.instagram.com/dementia_researcher/ https://www.facebook.com/Dementia.Researcher/ https://twitter.com/demrescommunity https://bsky.app/profile/dementiaresearcher.bsky.social https://www.linkedin.com/company/dementia-researcher

Episode 10 (February 23, 2024): Researchers from Francis Collins' lab developed an efficient CRISPR prime editing protocol to generate isogenic-induced pluripotent stem cell (iPSC) lines carrying heterozygous or homozygous alleles for putatively causal single nucleotide variants. An RNA-based system known as PRINT can create and introduce site-specific, safe, and stable transgenes into the human genome. Astellas Pharma and Kelonia announced a nearly $800 million research collaboration and license agreement to develop innovative universal, off-the-shelf in vivo CAR T cell therapies. Fourth-quarter earnings and revenue fell short of expectations as Biogen worked to eliminate 1,000 jobs (11.5% of its workforce), among other cost-cutting actions, and restructured its pipeline after a slow start. Plus, an interview with Andrea Choe, founder and chief executive officer at Holoclara. Listed below are key references to the GEN stories, media, and other items discussed in this episode of Touching Base: Generation of Human Isogenic Induced Pluripotent Stem Cell Lines with CRISPR Prime EditingThe CRISPR Journal, February 14, 2024 Addressing Scientific Misconduct: An Interview with Elisabeth BikBy Uduak Thomas, GEN Biotechnology, February 15, 2024 StockWatch: Biogen's Q4 Results Disappoint AnalystsBy Alex Philippidis, GEN Edge, February 18, 2024 Astellas and Kelonia Partner for $800M In Vivo CAR T Cell TherapiesBy Jonathan D. Grinstein, PhD, GEN Edge, February 20, 2024 PRINT: Precise RNA-Mediated Insertion of TransgenesGEN, February 21, 2024 Hosted on Acast. See acast.com/privacy for more information.

Travis Hardcastle and Seth Hanson answer questions from a webinar where they discuss innovative applications of CRISPR and iPSCs in disease modeling and drug discovery.

Anabella Nakhle from the University of Ottawa interviews Dr. Stephanie Willerth. Dr. Stephanie Willerth is the CEO of Axolotl Biosciences, a 3D bioprinting company  in Victoria, BC. She is also a a Canada research chair and full professor of Biomedical Engineering at the University of Victoria, and an Adjunct Professor at the University of Missouri. In this episode, Dr. Willerth shares about her research in developing a 3D bioprinted Alzheimers disease model that replicated the native tissue environment. Learn more: https://www.engr.uvic.ca/~willerth/ https://www.axolotlbiosciences.com/ Anabella Nakhle (Voice), Serena Solari, Elie Njeime, and Mathania Vuningoma (Post-production, graphic designer and producer)0:06| BeaTs and host introduction. 0:29 | Topic introduction. 0:59| Introduction to Dr. Willerth1:47| Introduction to 3D bioprinting and bioink that was used for the disease model2:43|Why was alzheimer's used as the disease model in this paper?3:55 |Differences in modeling  parkinson's disease vs alzheimer's disease.4:30| Cell viability in the bioink5:20| markers for cell death6:00 | The future and challenges of 3D bioprinting in disease model development7:14| Ethical issues that are faced with using patient-derived tissue8:55| Ensuring the genotype of the induced pluripotent stem cells (iPSCs)10:20| membrane potential of the bioprinted cells11:10| Future involvement in the bioprinting field for listenersSoundtrack by Funky Giraffe. All rights reserved. Listen more: https://open.spotify.com/track/1ZOKcgiydsTA6OVdkraVN5https://artlist.io/royalty-free-music/song/are-you-ready-for-me-baby/63852  

Sorry, folks, it's official: it's the end of sex.* Henry “Hank” Greely, Professor by courtesy of Genetics at Stanford School of Medicine, Deane F. and Kate Edelman Johnson Professor of Law, and Director of the Center for Law and the Biosciences, is very interested in how new biomedical technologies impact assisted reproduction. He's authored two books: The End of Sex and the Future of Human Reproduction in 2016, and CRISPR People: The Science and Ethics of Editing Humans, which published in 2021, and is Chair of the Steering Committee of the Center for Biomedical Ethics, among other impressive mouthfuls. In this episode, Ruby, Anne, and Hank dive into the changes that are already happening in human reproduction — and the possible changes to come. In addition to the scientific challenges, what are the ethical and legal questions we'll need to tackle as the landscape changes? Many of us became aware of genetic questions with Dolly the cloned sheep and the controversy over stem cells and how they might be used to repair damaged bodies. But Hank took the question even further, asking, What happens when we can make eggs and sperm from skin cells? Does that signal the end of human reproduction as we know it? Hank can pinpoint the origin of his curiosity to October 19, 2010 in Muenster, Germany — a conference talk on how induced pluripotent stem cells (iPscs) could be used to make other cells, including, the speaker said off-handedly, sperm and eggs. Wait, what? Science fiction? Maybe not. If you're curious about the possible future of fertility (and sex), this is the episode for you. Be sure to check out the book as well. There's not only theory about what the future could hold but also a well-researched history of how we've gotten here  As always, please rate and review, and most of all, share the episode and show with anyone you think could benefit.  *Spoiler: New technologies might mean the end of sex for reproduction and the start of sex purely for pleasure. So the news isn't bad after all.  Learn more about Hank Greely on the Stanford Law School Directory: https://law.stanford.edu/directory/henry-t-greely/ Find more episodes from Ruby and Anne at https://thewholepineapple.com.   Resources mentioned: Purchase the book from the Harvard University Press: https://www.hup.harvard.edu/catalog.php?isbn=9780674984011 Episode 29: My Embryos are Mosaic? https://thewholepineapple.com/episode-29-my-embryos-are-mosaic-interpreting-your-pgt-results/  

Autologous cell treatments are already making an impact in our lives today but the truth is we are only just scratching the surface of what might be possible. In our lifetime, aesthetic regenerative medicine will make a dramatic leap forward. The problem is that as our cells age they become less potent. That means many of us will never be able to experience the full impact of emerging regenerative innovation. On episode no. 85 of the Technology of Beauty we hear from the CEO of a startup that has not only set out to solve this problem, but already has a solution in the marketplace designed to prepare today's generation for the regenerative advances ahead. Meet Acorn Biolabs — The first non-invasive solution to preserve your younger follicle cells for use in regenerative medicine.From locking in cell age with cryogenic preservation to developing a process for autologous cell regeneration that could speculatively allow for 3D-printing a pancreas, Acorn CEO Drew Taylor describes it all so clearly that it feels less like science fiction, and more like inevitable future fact.But if it still seems too far off, or too good to be true, the first applications for these autologous cell-based therapies lie squarely in the realm of aesthetic medicine, where they are currently testing applications for their first cell-derived product composed of iPSCs — induced pluripotent stem cells.Find out what it all means and stick around for a demonstration of the harvesting procedure on Dr. Grant Stevens himself on the latest episode of The Technology of Beauty.» Apple Podcasts | https://podcasts.apple.com/us/podcast/technology-of-beauty/id1510898426» Spotify | https://open.spotify.com/show/0hEIiwccpZUUHuMhlyCOAm» Recent episodes | https://www.influxmarketing.com/technology-of-beauty/» Instagram | https://www.instagram.com/thetechnologyofbeauty/» LinkedIn | https://www.linkedin.com/company/the-technology-of-beauty/The Technology of Beauty is produced by Influx Marketing, The Digital Agency for Aesthetic Practices. https://www.influxmarketing.com/Want more aesthetic insights? Subscribe to Next Level Practices, the show where we discuss the ever-changing world of digital marketing and patient acquisition and bring you the latest ideas, strategies, and tactics to help you take your practice to the next level. https://www.influxmarketing.com/next-level-practices/

Today, you'll learn about how researchers are using stem cells to cure infertility in mice, the health benefits of honey made by ants, and the potential emotional toll of using AI at work. Ovarian Failure Cure “Stem Cell Therapy Restores Fertility in Mouse Model.” by Katie Brighton. 2023. https://www.technologynetworks.com/tn/news/stem-cell-therapy-restores-fertility-in-mouse-model-376618“Fertility restoration in mice with chemotherapy induced ovarian failure using differentiated iPSCs.” by Kevin M. Elias, et al. 2023. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00280-3/fulltext“Pathogenesis and Causes of Premature ovarian Failure: An Update.” by Mahbod Ebrahimi, M.D. & Firoozeh Akbari Asbagh, M.D. 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059950/“Mechanisms of epigenetic memory.” by Agustina D'Urso & Jason H. Brickner. 2014. https://www.sciencedirect.com/science/article/abs/pii/S0168952514000584Honeypot Ants “Western science catches up with First Nations' medicinal use of ant honey.” The University of Sydney. 2023. https://www.scimex.org/newsfeed/western-science-catches-up-with-first-nations-medicinal-use-of-ant-honey“Honeypot Ant Facts.” Fact Animal. N.d. https://factanimal.com/honeypot-ant/“Honeypot Ant: Good At Sharing.” San Diego Zoo Wildlife Explorers. 2023. https://sdzwildlifeexplorers.org/animals/honeypot-antAI Insomnia“Loneliness, insomnia linked to work with AI systems.” American Psychological Association. 2023. https://www.sciencedaily.com/releases/2023/06/230612114659.htm“Loneliness, insomnia linked to work with AI systems.” American Psychological Association. 2023. https://www.apa.org/news/press/releases/2023/06/loneliness-insomnia-ai-systems Hosted on Acast. See acast.com/privacy for more information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551374v1?rss=1 Authors: Ishioka, M., Nihashi, Y., Sunagawa, Y., Umezawa, K., Shimosato, T., Kagami, H., Morimoto, T., Takaya, T. Abstract: An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect of iSN04 on murine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In the undifferentiated state, iSN04 inhibited the proliferation of ESCs and iPSCs but did not affect the expression of pluripotent markers. In the differentiating condition, iSN04 treatment of ESCs/iPSCs from day 5 onward dramatically induced the differentiation into Nkx2-5+ beating cardiomyocytes with upregulation of Gata4, Isl1, and Nkx2-5, whereas iSN04 treatment from earlier stages completely inhibited cardiomyogenesis. RNA sequencing revealed that iSN04 treatment from day 5 onward contributes to the generation of cardiac progenitors by modulating the Wnt signaling pathway. Immunostaining showed that iSN04 suppressed the cytoplasmic translocation of nucleolin and restricted it to the nucleoli. These results demonstrate that nucleolin inhibition by iSN04 facilitates the terminal differentiation of cardiac mesoderm into cardiomyocytes, but interferes with the differentiation of early mesoderm into the cardiac lineage. This is the first report on the generation of cardiomyocytes from pluripotent stem cells using a DNA aptamer. Since iSN04 did not induce hypertrophic responses in primary-cultured cardiomyocytes, iSN04 would be useful and safe for the regenerative therapy of heart failure using stem cell-derived cardiomyocytes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.28.550873v1?rss=1 Authors: Glass, M. R., Waxman, E. A., Yamashita, S., Lafferty, M., Beltran, A., Farah, T., Patel, N. K., Matoba, N., Ahmed, S., Srivastava, M., Drake, E., Davis, L. T., Yeturi, M., Sun, K., Love, M. I., Hashimoto-Torii, K., French, D. L., Stein, J. L. Abstract: Background: Reproducibility of hCO phenotypes remains a concern for modeling neurodevelopmental disorders. While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types in multiple cell lines at one site, variability across sites using a harmonized protocol has not yet been evaluated. We present an hCO cross-site reproducibility study examining multiple phenotypes. Methods: Three independent research groups generated hCOs from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol. scRNA-seq, 3D fluorescent imaging, phase contrast imaging, qPCR, and flow cytometry were used to characterize the 3 month differentiations across sites. Results: In all sites, hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions with moderate to high fidelity to the in vivo brain that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and morphology. Differential gene expression showed differences in metabolism and cellular stress across sites. Although iPSC culture conditions were consistent and iPSCs remained undifferentiated, primed stem cell marker expression prior to differentiation correlated with cell type proportions in hCOs. Conclusions: We identified hCO phenotypes that are reproducible across sites using a harmonized differentiation protocol. Previously described limitations of hCO models were also reproduced including off-target differentiations, necrotic cores, and cellular stress. Improving our understanding of how stem cell states influence early hCO cell types may increase reliability of hCO differentiations. Cross-site reproducibility of hCO cell type proportions and organization lays the foundation for future collaborative prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.21.550059v1?rss=1 Authors: Muhammad, Z., Brown, P. W., Babazau, L., Alkhamis, A. I., Goni, B. W., Nggada, H. A., Mbaya, K. M., Wray, S., Marte, I. H., Karch, C., Serpell, L., Maina, M. B. Abstract: Genetic backgrounds contribute to cellular phenotypes, drug responsiveness, and health outcomes. However, the majority of human induced pluripotent stem cell (iPSC) lines are derived from individuals of European descent. Thus, there is a major, unmet need in the generation, characterisation, and distribution of iPSCs from diverse ancestries. To begin to address this need, we have generated iPSCs from dermal fibroblasts isolated from a healthy 60-year-old indigenous Nigerian male belonging to the Babur ethnic group. The iPSCs were generated using Sendai virus, and copy number variation (CNV) analysis revealed no new major abnormalities compared to the parental fibroblasts. The iPSCs have been characterised for pluripotency markers and morphology and successfully differentiated into neural progenitor cells and astrocytes. This iPSC line could serve as a healthy control in comparative studies and can be used in disease modelling, toxicity assessments, genetic analyses, and drug discovery processes within an African genetic background. To bolster the inclusion of African models in biomedical research, this iPSC line will be made available to the broader scientific community. Ongoing efforts focus on generating more lines from diverse indigenous populations towards creating a dedicated open-access African iPSC biobank. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549581v1?rss=1 Authors: Nguyen, V., Kravitz, J., Gao, C., Hochman, M. L., Meng, D., Chen, D., Wang, Y., Jegga, A. G., Nelson, S., Tan, W. Abstract: Port Wine Birthmark (PWB) is a congenital vascular malformation in the skin, occurring in 1-3 per 1,000 live births. We recently generated PWB-derived induced pluripotent stem cells (iPSCs) as clinically relevant disease models. The metabolites associated with the pathological phenotypes of PWB-derived iPSCs are unknown, which we aimed to explore in this study. Metabolites were separated by ultra-performance liquid chromatography and were screened with electrospray ionization mass spectrometry. Orthogonal partial least-squares discriminant analysis, multivariate and univariate analysis were used to identify differential metabolites (DMs). KEGG analysis was used for the enrichment of metabolic pathways. A total of 339 metabolites were identified. There were 22 DMs confirmed with 9 downregulated DMs including sphingosine and 13 upregulated DMs including glutathione in PWB iPSCs as compared to controls. Pathway enrichment analysis confirmed the upregulation of glutathione and downregulation of sphingolipid metabolism in PWB-derived iPSCs as compared to normal ones. We next examined the expression patterns of the key factors associated with glutathione metabolism in PWB lesions. We found that hypoxia-inducible factor 1 (HIF1), glutathione S-transferase Pi 1 (GSTP1), {gamma}-glutamyl transferase 7 (GGT7), and glutamate cysteine ligase modulatory subunit (GCLM) were upregulated in PWB vasculatures as compared to blood vessels in normal skins. Our data demonstrate that there are perturbations in sphingolipid and cellular redox homeostasis in the PWB vasculature, which may facilitate cell survival and pathological progression. Our data imply that upregulation of glutathione may contribute to laser-resistant phenotypes in the PWB vasculature. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.15.549177v1?rss=1 Authors: M, S., Paul, P., Ramakrishna, S., Ghose, V., Dey, G., Muddashetty, R., Jain, S., Purushottam, M., Viswanath, B., Sud, R. Abstract: ApoE4 isoform contributes to increased risk for Alzheimers Disease (AD) over the life course of individuals. Much remains unknown about the biological pathways that connect APOE4 genotype with the development of pathology that eventually leads to AD, nor do we know how early in life these cellular alterations begin. To answer these questions, we derived neural precursor cells (NPCs) from induced pluripotent stem cells (IPSCs) that were CRISPR-edited at the APOE locus. We intended to characterize the protein expression landscape in the NPCs subsequent to targeted deletion of E4 from a parent IPSC line of APOE3/4 genotype. Differentially expressed proteins (DEPs) following mass spectrometric analysis were determined from the protein abundance fold change values obtained for each protein. Proteins which showed greater than 1.5-fold difference with FDR adjusted P-value less than 0.05 were considered differentially expressed. DEPs were mapped to the STRING database (v11.5) for retrieval of interacting proteins and functional enrichment. CRISPR-editing of E4 from the parent line revealed 98 differential expressed proteins. Of these, 54 were upregulated, and 44 were downregulated. Further analysis of the DEPs via STRING database showed that these changes primarily affect pathways linked to RNA processing, plasma membrane repair, and cytoskeleton organization. Indeed, we find the effects of E4 extend beyond proteins considered central to AD pathology. Knowing more about the protein interactions regulated by ApoE, in an isoform-specific manner, can reveal new mechanistic insights into development of AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In a groundbreaking study, researchers have unlocked a new frontier in the fight against aging and age-related diseases. The study, conducted by a team of scientists at Harvard Medical School, has published the first chemical approach to reprogram cells to a younger state. Previously, this was only achievable using a powerful gene therapy. On July 12, 2023, researchers Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair from Harvard Medical School, University of Maine and Massachusetts Institute of Technology (MIT) published a new research paper in Aging, titled, “Chemically induced reprogramming to reverse cellular aging.” The team's findings build upon the discovery that the expression of specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs). This Nobel Prize-winning discovery raised the question of whether it might be possible to reverse cellular aging without causing cells to become too young and turn cancerous. In this new study, the researchers screened for molecules that could, in combination, reverse cellular aging and rejuvenate human cells. They developed high-throughput cell-based assays to distinguish young cells from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. In an exciting discovery, the team has identified six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week. The Harvard researchers previously demonstrated that it is indeed possible to reverse cellular aging without uncontrolled cell growth by virally-introducing specific Yamanaka genes into cells. Studies on the optic nerve, brain tissue, kidney, and muscle have shown promising results, with improved vision and extended lifespan observed in mice and, recently, a report of improved vision in monkeys. The implications of this new discovery are far-reaching, opening avenues for regenerative medicine and, potentially, whole-body rejuvenation. By developing a chemical alternative to age reversal via gene therapy, this research could revolutionize the treatment of aging, injuries and age-related diseases and offers the potential for lower costs and shorter timelines in development. On the heels of positive results in reversing blindness in monkeys in April 2023, preparations for human clinical trials of the lab's age reversal gene therapy are in progress. “Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it,” said David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. “This process has previously required gene therapy, limiting its widespread use.” The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality. “This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said. Press Release: https://www.aging-us.com/news_room/NEW-STUDY-Discovery-of-Chemical-Means-to-Reverse-Aging-and-Restore-Cellular-Function DOI: https://doi.org/10.18632/aging.204896 Corresponding Author: David A. Sinclair - david_sinclair@hms.harvard.edu Visit https://www.Aging-US.com​​ and connect with us on social media. MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.08.548192v1?rss=1 Authors: Aguilan, J., Pedrosa, E., Dolstra, H., Nur Baykara, R., Barnes, J., Zhang, J., Sidoli, S., Lachman, H. Abstract: Background: Jansen de Vries Syndrome (JdVS) is a rare neurodevelopmental disorder (NDD) caused by gain-of-function (GOF) truncating mutations in PPM1D exons 5 or 6. PPM1D is a serine/threonine phosphatase that plays an important role in the DNA damage response (DDR) by negatively regulating TP53 (P53). JdVS-associated mutations lead to the formation of a truncated PPM1D protein that retains catalytic activity and has a GOF effect because of reduced degradation. Somatic PPM1D exons 5 and 6 truncating mutations are well-established factors in a number of cancers, due to excessive dephosphorylation and reduced function of P53 and other substrates involved in DDR. Children with JdVS have a variety of neurodevelopmental, psychiatric, and physical problems. In addition, a small fraction has acute neuropsychiatric decompensation apparently triggered by infection or severe non-infectious environmental stress factors. Methods: To understand the molecular basis of JdVS, we developed an induced pluripotent stem cell (iPSC) model system. iPSCs heterozygous for the truncating variant (PPM1D+/tr), were made from a patient, and control lines engineered using CRISPR-Cas9 gene editing. Proteomics and phosphoprotemics analyses were carried out on iPSC-derived glutamatergic neurons and microglia from three control and three PPM1D+/tr iPSC lines. We also analyzed the effect of the TLR4 agonist, lipopolysaccharide, to understand how activation of the innate immune system in microglia could account for acute behavioral decompensation. Results: One of the major findings was the downregulation of POGZ in unstimulated microglia. Since loss-of-function variants in the POGZ gene are well-known causes of autism spectrum disorder, the decrease in PPM1D+/tr microglia suggests this plays a role in the neurodevelopmental aspects of JdVS. In addition, neurons, baseline, and LPS-stimulated microglia show marked alterations in the expression of several E3 ubiquitin ligases, most notably UBR4, and regulators of innate immunity, chromatin structure, ErbB signaling, and splicing. In addition, pathway analysis points to overlap with neurodegenerative disorders. Limitations: Owing to the cost and labor-intensive nature of iPSC research, the sample size was small. Conclusions: Our findings provide insight into the molecular basis of JdVS and can be extrapolated to understand neuropsychiatric decompensation that occurs in subgroups of patients with ASD and other NDDs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Emer Cooke may have already cemented her legacy as executive director of EMA through her leadership of the European regulator during the COVID-19 crisis. But she still faces a big task in navigating the agency through Europe's new pharma legislation, said Washington Editor Steve Usdin on the latest BioCentury This Week podcast. Usdin and colleagues discuss a wide-ranging fireside chat held last week in Amsterdam with Cooke, including how the agency adapted post-Brexit and the differences that need to be appreciated between the European and U.S. regulators.BioCentury's editors also discuss the future of induced pluripotent stem cells (iPSCs) in cell therapies, a conversation with Forbion's Wouter Joustra, a management buyout of SVB Securities, and why Senate Democrats are holding back on confirming a new NIH director.

Charlene Smith bio: "I am a project scientist in the lab of Dr Leslie Thompson at UC Irvine. I have worked here for 8 years studying Huntington's disease using HD patient derived stem cells. During that time I have received funding from the Hereditary Disease Foundation and the Huntington's Disease Society of America. I graduated in 2015 with my PhD from Cardiff University and wanted to pursue research in Huntington's disease." Gong-Her Wu bio: "In 2015, I proudly earned my Ph.D. from Tsing Hua University, marking a significant milestone in my academic journey. Subsequently, I had the privilege of joining the esteemed lab of Dr. Wah Chiu, where I expanded my expertise further and contributed to cutting-edge research. From 2019 to 2023, I was fortunate to receive support from the Hereditary Disease Foundation (HDF), a valuable recognition of my work's importance and potential impact. Now, I am a research scientist at Stanford University, working in the esteemed lab of Dr. Wah Chiu. Over the past six years, my focus has been on advancing the field of cryo-electron tomography (cryo-ET) and its application in studying Huntington's disease. I have employed various model systems to achieve this, including yeast, induced pluripotent stem cells (iPSCs), primary neurons, C. elegans, and mouse brains." Link to research: https://www.nature.com/articles/s41467-023-36096-w Link to Hereditary Disease Foundation: https://www.hdfoundation.org/

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Mina Fares, Dr. Johannes Bergehr, and Dr. Christina Peter from Cambridge University Hospitals in the UK. They discuss a case involving a man man in his 40's presented with progressive heart failure symptoms. He has extensive background cardiac history including prior episodes of myocarditis and complete heart block status post permanent pacemaker implantation. Ultimately a diagnosis of Danon disease is made. Dr. Sharon Wilson provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Hirsh Elhence. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases', with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Summary - A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University A man in his 40s with a history of cardiac issues, including prior myocarditis and complete heart block, presented with progressive heart failure symptoms. Extensive cardiac investigations were conducted, revealing dilated left ventricle, mild to moderate left ventricular systolic dysfunction, normal coronaries, infero-lateral late gadolinium enhancement on cardiac MRI, and low-level uptake on PET-CT. Differential diagnosis included worsening underlying cardiomyopathy, recurrent myocarditis, tachycardia-related cardiomyopathy, pacemaker-induced LV dysfunction, and sarcoidosis. The patient's condition improved with heart failure medications, and cardiac MRI showed a mildly dilated left ventricle with moderate systolic dysfunction and active inflammation in the anterior wall. Further evaluation indicated a family history of hereditary cardiomyopathy, and the patient exhibited phenotypic features such as early-onset heart disease, arrhythmias, family history of cardiomyopathy, learning problems, intellectual disability, and mild proximal myopathy. Genetic testing confirmed a LAMP2 mutation, leading to the diagnosis of Danon disease. Case Media - A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University Show Notes -A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University References - Danon, M. J., Oh, S. J., DiMauro, S., Miranda, A., De Vivo, D. C., & Rowland, L. P. (1981). Lysosomal glycogen storage disease with normal acid maltase. Neurology, 31(1), 51-7. Nishino, I., Fu, J., Tanji, K., Nonaka, I., & Ozawa, T. (2000). Mutations in the gene encoding LAMP2 cause Danon disease. Nature, 406(6798), 906-10. Tanaka, K., Nishino, I., Nonaka, I., Fu, J., & Ozawa, T. (2000). Danon disease is caused by mutations in the gene encoding LAMP2, a lysosomal membrane protein. Nature, 406(6798), 902-6. Maron, B. J., Haas, T. S., Ackerman, M. J., Ahluwalia, A., Spirito, P., Nishino, I., ... & Seidman, C. E. (2009). Hypertrophic cardiomyopathy and sudden death in a family with Danon disease. JAMA, 301(12), 1253-9. Hashem, S., Zhang, J., Zhang, Y., Wang, H., Zhang, H., Liu, L., ... & Wang, J. (2015). AAV-mediated gene transfer of LAMP2 improves cardiac function in Danon disease mice. Stem cells, 33(11), 2343-2350. Chi, L., Wang, H., Zhang, J., Zhang, Y., Liu, L., Wang, J., ... & Hashem, S. (2019). CRISPR/Cas9-mediated gene editing of LAMP2 in patient-derived iPSCs ameliorates Danon disease phenotypes.

In this podcast, we talked with Dr. Ma Sha, Head of Bioprocess Applications at Eppendorf SE about advancements and challenges in cell and gene therapy production along with solutions for scale up and transition to stirred-tank bioreactor suspension culture. We began the interview by talking about the biggest advancements in cell and gene therapy, including CAR T-cell therapy development, clinical results and FDA approvals. Another area of great advancement is induced Pluripotent Stem Cell (iPSC) Culture technique. Dr. Sha explained that it used to be very difficult to culture iPSCs until it was possible to culture iPSC suspension spheres in stirred-tank bioreactors, which was a big breakthrough in the cell and gene therapy area. I followed up by asking Dr. Sha what he sees as the major challenges in the development and production of cell and gene therapies that still need to be addressed. He said that one of the major breakthroughs has been the autologous therapies that have been approved, particularly CAR T-cell therapies. However, this has also been a major challenge, because the autologous model is not cost effective. As a result, there has been a shift toward developing allogeneic therapies and building this production model will be a major challenge moving forward. Another challenge on the manufacturing side is ensuring to follow Good Manufacturing Practice (GMP), as it has been a common request from cell and gene therapy companies. Next, I asked him about the move from 2D to 3D culture and his experiences with this transition. Dr. Sha shared that several of the projects that Eppendorf bioprocess works on start as 2D culture in flasks, it is a natural place to start for most of the cell lines since they are attachment cells. They must then be converted into suspension culture to enable 3D culture, since 2D culture significantly limits the yield and productivity. He went on to say that if you look back at the evolution of antibody production, it was important to convert production to suspension cell culture and this is also necessary for the cell and gene therapy field. Moving from 2D to 3D culture and especially utilizing stirred-tank bioreactors enables much higher yields. As it stands, the yield for cellular therapy cell production is fairly low, especially compared to the industry standard of CHO cells used for antibody production, so a lot of improvement needs to happen. We then discussed stirred-tank bioreactors and their increased use in cell and gene therapy development and production. I asked Dr. Sha what are the key factors that developers should consider when choosing stirred-tank bioreactors. He explained that stirred-tank bioreactors fit the model of allogeneic production. Autologous models are not suitable for stirred-tank bioreactors. Developer companies need to keep in mind that if they want to move to stirred tank bioreactor platform, they need the production model to be allogeneic. In addition, it is important to consider the support available with respect to scaling up and leveraging supplier experience. For example, Eppendorf bioprocess over the years has produced many application notes to help customers scale their manufacturing. They have even built model production systems in Eppendorf stirred-tank bioreactors. The program called “Scale up Assist” allows customers to skip much of the difficult calculations required to achieve reproducible yields when moving from smaller to larger vessels. Eppendorf has a very long history of working in protein-based therapeutic cell culture production and about ten years ago expanded to include cell and gene therapy. I asked Dr. Sha in his experiences, what are the most important takeaways in terms of areas that still need work and advancements on the horizon. For instance, what can we learn from protein-based therapy cell culture to apply to cell and gene therapy production? He said that he thought that allogeneic production is a great lesson learn...

A new research paper was published in Aging (Aging-US) Volume 14, Issue 24, entitled, “Transcriptomic analysis of human ALS skeletal muscle reveals a disease-specific pattern of dysregulated circRNAs.” Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. In this new study, researchers Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Ying Si, Allison B. Herman, Jen-Hao Yang, Abhishek Guha, Yulan Piao, Jinshui Fan, Jennifer L. Martindale, Rachel Munk, Xiaoling Yang, Supriyo De, Brijesh K. Singh, Ritchie Ho, Myriam Gorospez, and Peter H. King from the National Institutes of Health's National Institute on Aging, The University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, and Cedars-Sinai Medical Center set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, the researchers first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS compared to normal individuals. “By RT-qPCR analysis, we confirmed that 8 circRNAs were significantly elevated and 10 were significantly reduced in ALS, while the linear mRNA counterparts, arising from shared precursor RNAs, generally did not change.” Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, a subset of the circRNAs significantly elevated in ALS muscle biopsies were significantly reduced in the spinal cord samples from ALS patients and ALS (SOD1G93A) mice. In sum, the researchers identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies. “As our studies advance, we will investigate the function of the most promising and abundant circRNAs, among the 18 circRNAs reported here. We are especially interested in those that appeared to be specific for ALS (Figure 2), as they may help to characterize disease-associated molecular pathways that could be targeted therapeutically.” DOI: https://doi.org/10.18632/aging.204450 Corresponding Authors: Myriam Gorospe - GorospeM@grc.nia.nih.gov, Dimitrios Tsitsipatis - dimitrios.tsitsipatis@nih.gov, Peter H. King - phking@uabmc.edu Keywords: amyotrophic lateral sclerosis, circular RNAs, neurodegenerative disease, human skeletal muscle, human spinal cord tissue About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

BlueRock Therapeutics' President and CEO Seth Ettenberg, Ph.D. talks to Cell & Gene: The Podcast listeners about the company's Phase 1 Clinical Trial for Advanced Parkinson's Disease. Ettenberg also covers the most promising therapeutic applications for iPSCs currently in development as well as the major regulatory challenges that the field faces for their clinical use. We also cover how far iPSCs have come and what future progress may entail.

Dr. Robert Hollingsworth is the current Chief Scientific Officer of Shoreline Biosciences, a biopharmaceutical company developing next-generation cellular immunotherapies based on induced pluripotent stem cells (iPSCs)- utilizing its proprietary platforms. Dr. Hollingsworth joins Shoreline from Pfizer, where he served as Chief Scientific Officer and Vice President of Cancer Vaccines and Immunotherapeutics. Prior to Pfizer, he was Senior Director of Oncology Research at MedImmune where he led and advanced a large portfolio of more than twenty programs, including CAR-T programs, and contributed to the approval of durvalumab.  Before that, he held several R&D positions at GSK, Pharmacia, and Upjohn.In this episode, we discuss Robert's long career in biopharma, the platform technology being developed at Shoreline, and the role of strategic partnerships in early-stage development.Hosted by Gustavo Carrizo and Joe Varriale.

Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). This episode focuses on an abstract session Scott Friedman chaired on Thursday afternoon discussing advancing in the basic science of researching and understanding mechanisms surrounding fibrosis.Scott starts by describing the session he co-chaired with Sophie Lotersztajn of INSERM as "one of the most exciting groups of presentations I've seen in many years." During this episode, he leads the rest of the panel through exploration of all six presentations. These include:--Targeting the liver circadian clock by REV-ERB-alpha activation improves liver fibrosis by circadian gating of TGF-beta signaling, Atish Mukherji, University of Strasbourg. Scott describes this presentation, which demonstrates that stellate cells have a circadian clock, as "one of the most surprising results" in that circadian activity can be linked to the  "lowly stellate cell."  This paper generated significant conversation among the group, ranging from Neil Henderson's observation that circadian regulation is a powerful regulator of fibrotic processes to Jörn Schattenberg's observations about what this might mean for treating patients in the clinic to Roger Green asking whether this concept might be germane to specific drugs in development (Scott had mentioned that signalling occurred through TGFbeta.  Louise Campbell and Rachel Zayas  add comments about the relevance of circadian rhythm to care today and ways this paper might yield exciting new areas for research.--Stellate cell dynamics in progression and regression of hepatic fibrosis, Laura Almale del Barrio, Denmark. This presentation, funded in part by Novo Nordisk, focused on how mouse livers respond when researchers stop injuring them. It leads Neil to comment on how little attention researchers pay to scar healing relative to how much more they pay to the process of scar creation and injury. In response to a question from Scott, Neil also discusses how advances in spatial transcriptomic will make questions like these easier to research in the not-too-distant future. After this, Jörn goes on to note that the paper discussed 14 different stellate cell states, which he interprets as involves activation and transitioning processes. He asks what this might imply for treating patients in the clinic.The other four presentations engender a similar level of exploration. They include:--Peroxidasin deficiency re-programs macrophages toward pro-fibrolysis function and promotes collagen resolution in liver, Mozhdeh Sojoodi, Mass General Hospital and Harvard. --Machine learning methods for detailed characterization of TGF-beta-induced signatures in a large iPSC-derived hepatic stellate cell cohort, Kara Marie Liu, Insitro, United States--The proteomic analysis of hepatic stellate cell differentiation from iPSCs identifies RORalpha as an antifibrogenic target, Raquel A. Martinez Garcia de la Torre, Spain--Biliary epithelial cell-specific RAGE controls ductular reaction-mediated fibrosis during cholestasis, Macrina Lam, GermanyIn each case, Scott starts by discussing the historic of scientific progress that predates the particular paper and topic, places the presentation properly within that context, and invites the others to comment. Each Surfer has unique (and uniquely interesting) comments in their own areas of expertise.

In Sickle Cell Disease (SCD) patients, one of the most critical treatments is a blood transfusion. A blood transfusion is used to provide normal red blood cells to the patient's body. Red blood cell transfusions help lessen anemia and reduce the blood's viscosity, allowing it to flow more freely, ease disease symptoms and prevent complications. Alloimmunization is common in patients with SCD and may complicate transfusion therapy. For many patients, a close blood type match is essential and is found in donors of the same race or similar ethnicity. In this episode, learn why patient phenotyping and prophylactic matching to reduce alloimmunization is recommended for SCD patients and why donor source for blood donations of the same race or similar ethnicity is critical.   About the Speaker: Dr. Stella T. Chou is Chief of the Division of Transfusion Medicine, board-certified in Blood Banking and Transfusion Medicine, and an attending physician in the Division of Hematology at Children's Hospital of Philadelphia. Dr. Chou earned her medical degree from New York Medical College in Valhalla, NY. She specializes in caring for children with SCD, those who make antibodies against red blood cell transfusions (alloimmunization), and those requiring apheresis. Her research interests are focused on improving red blood cell matching for patients through the use of innovative tools. Her work has demonstrated that inheritance of variant blood group antigens in patients with SCD contributes to their high rate of red blood cell antibody formation. Her ongoing work focuses on the genetic matching of red blood cells and creating customized induced pluripotent stem cells (iPSCs) with rare blood group antigen combinations as renewable sources of red blood cell reagents to improve antibody identification and donor red blood cell matching. For her innovative research, she is a recipient of the National Blood Foundation Hall of Fame award. Dr. Chou is a worldwide recognized author and speaker with over 100 publications and lectures. In addition to her clinical work, Dr. Chou serves as an Associate Professor of Pediatrics at the Perelman School of Medicine, University of Pennsylvania.

https://marklwhite.com Most people are not aware that we all experience a huge metabolic switch between the ages of 15-25 that shifts our bodies from growth and into aging. Although experts have not been able to identify the cause behind this switch, leaders in the field of regenerative medicine, like Dr. Ian White, are on a mission to discover it with the goal of ending aging forever. During this fascinating episode, Dr. White and I cover the topics below: - The science of aging and age-related disease - Why we age and why we don't have to - The Unified Theory of LIFE: Evolution, aging and the future of regenerative medicine - Editing genes to rid disease - Billionaires & Mars: What's going to happen to the rest of us? *About Our Guest* Dr. White is an expert in the field of regenerative medicine and stem cell biology with over 20 years experience working in academia and industry. Dr. White received his B.S. from Liverpool John Moores University and his M.S. from the famed Liverpool School of Tropical Medicine in England before being hired at Dartmouth College in the United States to study the genetics of gamete biology. In August of 2000 Dr. White was recruited to Harvard University to work with hematopoietic stem cells (HSCs) and immune cell biology under the mentorship of the world-renowned Dr. Laurie Glimcher, where he co-authored several peer-reviewed scientific publications. Dr. White went on to receive his Ph.D. from the Ansary Stem Cell Institute, division of Regenerative Medicine at Cornell University under the guidance of Howard Hughes investigator Dr. Shahin Rafii. During this time Dr. White developed an in vitro method for culture expanding autologous HSCs in an artificial vascular niche for the treatment of cancer patients who have undergone bone marrow ablation following chemo- or radio-therapy. This technology has since gone on to be commercialized by Cornell and the company, Angiocrine, LLC, has become one of the top two HSC expansion companies in the US. Following the completion of his Ph.D., Dr. White spent time as a post-doctoral research scientist in the embryonic stem cell (ESC) laboratory of Dr. Stephen Dalton, whose pioneering work led to the inclusion of c-myc as one of the four factors used by Nobel award-winning Dr. Shinya Yamanaka in the generation of induced pluripotent stem cells (iPSCs). Subsequently, Dr. White relocated to the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine. Dr. White published ground-breaking research in the field of regenerative medicine alongside Dr. Joshua Hare, including a book chapter on the use of Mesenchymal Stem Cells (MSCs) in cardiac regeneration. In 2015, Dr. White's work on the regeneration of the heart was featured on the cover of Circulation Research, one of the top peer-reviewed journals for cardiovascular medicine in the world. In 2016. Dr. White was honored with an award for the “Best Manuscript” by the American Heart Association for this work, which highlighted the role of peripheral nerves in cardiac regeneration. Dr. White has lectured and published extensively in the field of stem cell biology, clinical stem cell applications and regenerative medicine. *Connect With Guest* Website: https://neobiosis.com LinkedIn: www.linkedin.com/in/ian-white-phd

Professor Anand Chandrasekhar will discuss the discovery of stem cells and ethical issues associated with research using embryonic stem cells. He will explain how ethical concerns related to stem cell research have receded due to the discovery of induced pluripotent stem cells (iPSCs). The impact of iPSCs and applications on personalized/precision medicine and research using model organisms will be discussed.

Read Paediatric Neurologist, Clinician-Scientist, Laureate Professor Ingrid Scheffer, AO's piece in the Lancet Neurology: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00002-3/fulltext Here is the quote Mike read: “It will not be feasible to design a gene therapy for each pathogenic variant of every genetic disease, so clever strategies, such as those mentioned earlier, will need to be developed to enable these life-changing therapies to reach a wide variety of patients. The future of child neurology is bright—indeed, far more promising than at the turn of the 21st century. Many devastating diseases now have real hope of targeted therapies, which can cure not just one but all manifestations of the disease and offer the child and family the promise of a normal life.” SRF article on IPSCs: https://www.syngapresearchfund.org/post/another-srf-contribution-to-syngap1-research-patient-derived-cell-lines-to-test-treatments SRF article on reading your genetic report: https://www.syngapresearchfund.org/post/understanding-your-genetic-report-with-syngap1-a-rare-disease SRF article on VUS: https://www.syngapresearchfund.org/post/does-your-genetic-report-contain-a-variant-of-unknown-significance-vus-in-syngap1 REMEMBER Raise funds at https://syngap.fund/give Subscribe to and rate this 10 minute #podcast #SYNGAP10 here https://syngap.fund/10 if you want a direct link for Apple: https://syngap.fund/10a Episode 44 of #Syngap10 - January 21, 2022 #missense #SYNGAP1 #F78A1 #Syngap #epilepsy #autism #intellectualdisability #id #raredisease #epilepsyawareness #autismawareness #rarediseaseresearch #SynGAPResearchFund #CareAboutRare #PatientAdvocacy #GCchat #Neurology #Genetics --- Send in a voice message: https://podcasters.spotify.com/pod/show/syngap10/message

Subscribe to the podcast! https://syngap.fund/10 = https://www.syngapresearchfund.org/syngap10-podcast We are making IPSCs! https://syngap.fund/ipsc = https://www.syngapresearchfund.org/post/another-srf-contribution-to-syngap1-research-patient-derived-cell-lines-to-test-treatments Join the largest SYNGAP1 study on earth https://syngap.fund/nhs Learn more at https://syngap.fund/rarex Watch our Webinars! https://syngap.fund/webinar = https://www.syngapresearchfund.org/families/resources/webinars - https://syngap.fund/aten Thurs June 10th @ 10 PST - https://syngap.fund/drtf Sat July 17th @ 9 PST - Learn more at https://syngap.fund/FrazierPR - and https://syngap.fund/Frazier My birthday fundraiser, please give, I will match every dollar: https://syngap.fund/m46 --- Send in a voice message: https://podcasters.spotify.com/pod/show/syngap10/message

SYNGAP10 - Ep. 10 - 14 May 2021 - Scales, Grands, Ciitizens, Kayo, iPSC Validated Scales - Congrats to the ORCA Team at Duke https://syngap.fund/orca - Join Dr. Frazier to learn more about the NET www.syngapresearchfund.org/families/resources/webinars Grand parents article https://syngap.fund/grand - Thank you Barbara for this article https://www.syngapresearchfund.org/post/loving-a-grandchild-with-syngap1 - Join the Group there is a link in the article - Peer connection is so key Ciitizen - US sign ups continue! Every patient matters/. https://www.ciitizen.com/syngap1/ - International is open! Same link, but you must collect and upload. Ashley Evans, the co-founder of SRF, gave an interview with Kayo - https://Syngap.fund/Kayo IPSCs - We are in the home stretch of accelerating treatments via making iPSCs available --- Send in a voice message: https://podcasters.spotify.com/pod/show/syngap10/message