The Genetics Podcast

Episódios

• 
  EP 251: Cracking the delivery barrier in genetic medicine with Jagesh Shah of Mirai Bio 06.08.2026 38min

  This week on The Genetics Podcast, Patrick is joined by Dr. Jagesh Shah, Chief Scientific Officer at Mirai Bio. They discuss why delivery is a central bottleneck holding back nucleic acid medicines, how Mirai's lipid nanoparticle (LNP) platform is built to reach tissues like adipocytes and T cells, and the machine learning feedback loop the company uses to engineer LNP formulations.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Jagesh01:40 Why delivery is the main bottleneck for gene therapies03:42 Easier vs harder tissues to target for delivery06:40 Overview of Mirai's modular delivery platform 09:02 Comparing viral vectors and lipid nanoparticles (LNPs) 12:18 Different approaches for targeting adipocytes and T cells with LNPs15:49 Mirai's machine learning (ML) feedback loop for optimizing LNP formulation20:50 Why lipid chemistry is still hard for ML to learn and factors affecting LNP tropism24:35 Jagesh's path from academia to Mirai27:23 Mirai's platform business model and how it lowers risk29:13 What industry partnerships with Mirai look like31:41 Mirai's next frontier of delivery to muscle tissue and the brain 34:40 Cargo size and immunogenicity of LNPs vs AAV 36:00 Why the field needs to close the regulatory pace gap 37:19 Closing remarksFind out more:Mirai Bio
• 
  EP 250: Redefining rare disease realities with Sharon Terry of the Genetic Alliance [Re-run] 30.07.2026 41min

  This week on The Genetics Podcast, Patrick is joined by Sharon Terry, President & CEO of Genetic Alliance. They discuss how Sharon established a layperson-led biobank, her long-term work on rare diseases and patient advocacy, and her program to bring genetic technology to patients in low- to middle-income countries. We’re re-running this episode for its enduring lessons on patient advocacy, rare disease parenting, communication, and citizen science. Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Sharon and a discussion of the personal experience with rare disease that started her journey03:47 Reasons Sharon decided to establish the first layperson-led biobank05:34 Challenges with setting up the biobank infrastructure07:00 Balancing financial factors in a non-profit organization 09:30 Recent patterns and future insight into rare disease drug discovery framework and regulation15:32 Barriers to widespread collaboration and cooperation in rare disease research, and why it should be approached from a public health perspective18:12 Background and experiences from the iHope Genetic Health program in low- to middle-income countries24:44 Sharon’s perspective on challenges with the Genetic Information Non-discrimination Act28:49 Sharon’s lessons learned in her patient advocacy and policy work, and her hopes for future legislation33:04 Sharon’s hopes for improved access to genetic testing and treatment for children in underserved communities34:34 How Sharon learned about rare diseases and genetics as a “homeschooling mom without a degree”37:54 Insights into how elements of spirituality can support advocacy work40:18 Closing remarks
• 
  EP 249: Building the world's most detailed genetic map of inflammatory bowel disease with Carl Anderson of the Wellcome Sanger Institute 23.07.2026 41min

  This week on The Genetics Podcast, Patrick is joined by Dr. Carl Anderson, Senior Group Leader and Head of the Human Genetics Programme at the Wellcome Sanger Institute, where he leads the Genomics of Inflammation and Immunity Group. They discuss IBDVerse, the single-cell atlas Carl's team built to map genetic effects on gene regulation across gut cell types, how coding and non-coding variants converge on shared biological pathways in inflammatory bowel disease, and Carl's vision for longitudinal multi-omics cohorts built around the sickest and most underrepresented hospital patients.Show Notes0:00 Intro to The Genetics Podcast00:58 Welcome to Carl02:05 The origins of IBDVerse and mapping genetic effects on gene regulation across gut cell types in IBD05:43 How anti-TNFs and newer genetically-supported IBD drugs have reshaped treatment 08:04 Genetic versus environmental contributions to IBD09:53 Using single-cell data to uncover IBD disease subtypes13:22 Drug sequencing and immunogenicity in treatment response16:52 The backstory of building the IBDVerse atlas at scale20:29 How coding and non-coding IBD variants converge on the same genes and pathways23:38 The case for pathway-specific polygenic risk scores28:17 Building a longitudinal multi-omics dataset to predict IBD progression and drug response30:08 Why Sanger's next cohort targets sick and underrepresented patients rather than healthy volunteers34:07 What Carl looks for when interviewing PhD students and faculty candidates 39:20 A call to junior scientists and closing remarksFind out more:IBDverse study
• 
  EP 248: The blood mutations rewriting cardiovascular risk: Clonal hematopoiesis and polygenic risk with Pradeep Natarajan of Massachusetts General Hospital 16.07.2026 48min

  This week on The Genetics Podcast, Patrick is joined by Dr. Pradeep Natarajan, Director of Preventive Cardiology at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. They discuss the discovery of clonal hematopoiesis as a driver of cardiovascular disease, the inflammatory mechanisms and emerging therapies targeting it, the growing clinical case for polygenic risk scores, and Pradeep's upcoming move to lead cardiometabolic and human genetics research at Amgen.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Pradeep01:30 The origin story of clonal hematopoiesis (CH) as a cardiovascular risk factor 09:41 CH mutations such as TET2 that are linked to cardiovascular disease12:27 Evidence tying inflammation to CH and drugs that could target it16:49 TenSixteen Bio’s strategy for targeting CH and the challenge of finding the right patients21:33 Trajectory of CH across age and somatic mosaicism beyond blood26:44 How polygenic risk scores fill a gap in cardiovascular risk prediction34:49 The future clinical applications of polygenic risk scores39:20 The challenge of standardizing polygenic risk scores for clinical and regulatory use42:27 Pradeep's move to pharmaceutical company Amgen and his reasons for it46:23 Closing remarksFind out more:Clonal hematopoiesis paper
• 
  EP 247: Why neurons accumulate mutations like clockwork: Somatic mosaicism and neurodegeneration with Christopher Walsh of Boston Children's Hospital 09.07.2026 37min

  This week on The Genetics Podcast, Patrick is joined by Dr. Christopher Walsh, Professor of Pediatrics and Neurology at Harvard Medical School, Chief of Genetics and Genomics at Boston Children's Hospital, and HHMI Investigator. They discuss his path from neurobiology to human genetics, how somatic mosaicism in the brain drives disease from epilepsy to Alzheimer's, and what this reveals about new therapeutic targets for neurodegeneration.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Chris01:18 Chris’ path from neurobiology to human genetics04:55 How collaboration and mentorship have shaped Chris' career06:59 Somatic mosaicism and genetic mutations in the brain, from epilepsy to Alzheimer’s13:56 Repurposing cancer therapeutics and targeting DNA damage as new approaches to Alzheimer's15:29 A shared pattern of DNA damage across neurodegenerative diseases and the mechanism behind it19:36 How healthy neurons accumulate mutations with age and what that means for the brain23:21 How mutation rates and patterns vary across cell types26:23 How genome quality control and synaptic pruning may explain both brain development and neurodegeneration30:33 Why some people maintain a healthy brain into old age33:57 Chris’ advice for early-career scientists on pursuing goals36:43 Closing remarksFind out more:https://walshlab.org/
• 
  EP 246: Turning a fatal diagnosis into a cure strategy: Accelerating C9orf72 ALS research with Yentli Soto Albrecht of CureC9 02.07.2026 34min

  This week on The Genetics Podcast, Patrick is joined by Yentli Soto Albrecht, physician-scientist in training and founder of CureC9. They discuss how losing her father to C9orf72 ALS, and later learning her own genetic risk, reshaped the direction of her career. The conversation explores the biology linking the C9 repeat expansion to ALS and FTD, and how CureC9 is removing barriers across biomarkers, therapeutics, and patient samples to accelerate progress toward a cure.Show Notes0:00 Intro to The Genetics Podcast00:58 Welcome to Yentli02:34 How Yentli's father's C9 ALS diagnosis and her own genetic risk led her to pivot her research career toward curing it06:41 The biology of the C9orf72 repeat expansion and how TDP-43 dysregulation links it to ALS and FTD11:40 Therapeutic strategies targeting TDP-43 pathology in ALS and FTD15:35 The state of biomarkers for ALS and FTD, and why C9-FTD trials lag behind ALS22:08 How Yentli is lowering barriers for biomarker, cell line, and drug development through CureC930:40 Call for collaborators and where to follow Yentli 32:59 Closing remarksFind out more: CureC9
• 
  EP 245: Developing targeted therapies for ALS with Eric Green of Trace Neuroscience [Re-run] 25.06.2026 43min

  This week on The Genetics Podcast, we're re-airing our conversation with Eric Green, Founder and CEO of Trace Neuroscience, Co-Founder and Chief Scientific Officer at Maze Therapeutics, and Adjunct Clinical Assistant Professor at Stanford University School of Medicine. Patrick and Eric discuss Eric's transition from cardiology to entrepreneurship, the role of highly focused biotechs in creating precision therapies, and the development of high-impact gene therapies for people with amyotrophic lateral sclerosis (ALS). We're revisiting this episode following Trace Neuroscience's recent announcement that the first patient has been dosed with its antisense oligonucleotide (ASO) designed to restore UNC13A function in ALS.Show Notes0:00 Intro to The Genetics Podcast02:03 Welcome to Eric, his background in cardiology, and how he got into biotech06:23 Eric’s experience incubating and spinning out early-stage companies with Third Rock Ventures and developing Maze Therapeutics09:13 Eric’s decision to transition from academia to the world of biotech11:24 Building Maze Therapeutics and Eric’s focus on and genetic modifiers to discover new drugs   15:09 The growth of therapeutic modalities in the context of genetics and gene therapies16:48 What led Eric to launch Trace Neuroscience to develop ALS therapies28:35 The process of getting Trace’s ALS therapies into the clinic32:22 The identification of therapeutic value in low odds ratio genes35:58 Eric’s view on the APOA1 gene target and its major effect size in kidney disease40:03 How best to integrate genetics and genetic discovery into small and medium biotechs41:50 Closing remarksFind out moreTrace Neurosciencehttps://www.businesswire.com/news/home/20260622451252/en/Trace-Neuroscience-Initiates-Global-Clinical-Development-Program-for-TRCN-1023-an-Antisense-Oligonucleotide-Designed-to-Restore-UNC13A-Function-for-the-Treatment-of-ALS
• 
  EP 244: Building the first n-of-1 ASO: The new frontier of rare disease with Timothy Yu of Boston Children’s Hospital 18.06.2026 44min

  This week on The Genetics Podcast, Patrick is joined by Dr. Timothy Yu, Associate Professor of Pediatrics at Harvard Medical School and Physician/Researcher at Boston Children’s Hospital. They discuss how one child’s hidden genetic mutation led Tim into individualized ASO medicine, what it takes to develop n-of-1 therapies, and how new regulatory frameworks could expand treatment options for children with ultra-rare genetic disease.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Tim02:05 How uncovering the genetic mutation underlying an ultra-rare disease led Tim into personalized ASO medicine07:38 Challenges in developing a custom ASO 12:25 How Tim’s team has scaled individualized ASO therapies to reach more than 50 patients worldwide16:18 Measuring clinical benefit in n-of-1 therapies with natural history data, wearables, and biomarkers20:24 How the N-of-1 Collaborative helps rare disease researchers share infrastructure 24:28 Comparing ASOs, base editing, and prime editing for individualized rare disease therapies30:06 Finding scalable models for n-of-1 therapies in newborn genetic disease33:52 The potential impact of the FDA’s Plausible Mechanism framework on bespoke therapies36:58 Connecting rapid newborn genome sequencing to earlier treatment for rare genetic disease42:10 Closing remarks
• 
  EP 243: How BD² is using genetics and deep phenotyping to transform bipolar research with Cara Altimus and Ben Neale 11.06.2026 47min

  This week on The Genetics Podcast, Patrick is joined by Dr. Cara Altimus, CEO of BD², and Dr. Benjamin Neale, Associate Professor at Harvard Medical School and Massachusetts General Hospital. They discuss how rare variant discovery is opening new routes into bipolar disorder biology, how BD² is combining genetics with longitudinal multimodal data, and how patient priorities are shaping a research model focused on faster diagnosis and more precise treatments.Show Notes0:00 Intro to The Genetics Podcast00:58 Welcome to Cara and Ben01:57 The origin and aims of BD2 04:20 Major knowledge gaps in bipolar disorder genetics06:43 Using genetics and deep phenotyping to map bipolar disorder biology13:47 Why bipolar disorder genetics needs both scale and deep clinical data17:32 Finding the most predictive data for bipolar disorder biology and care19:19 The search for scalable biomarkers in bipolar disorder21:35 How BD² is building a bridge from discovery to clinical trials26:48 Why bipolar diagnosis takes years and what patients want research to solve33:08 How BD² is looking to other programs as inspiration to build a new research model35:31 What overlapping risk genes reveal across bipolar disorder, schizophrenia, and autism37:40 How rare variants could de-risk precision psychiatry trials41:25 How BD² is scaling from early milestones to global funder momentum45:04 Closing remarks Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_linkFind out more:BD2
• 
  EP 242: Connecting dementia research, policy, and patient communities with Angela Bradshaw of Alzheimer Europe [Re-Run] 04.06.2026 42min

  This week on The Genetics Podcast, Patrick is joined by Dr. Angela Bradshaw, Director for Research at Alzheimer Europe and honorary lecturer at the University of Glasgow. Following a series of recent episodes exploring Alzheimer’s disease research, we’re revisiting this conversation to bring in an essential patient advocacy and nonprofit perspective on the field. Patrick and Angela discuss how Alzheimer Europe partners in and supports pan-European dementia research, the heterogeneity of dementia and Alzheimer’s disease, the future of potential new gene therapies, and the critical role advocacy organizations play in ensuring research reflects the needs and priorities of patient communities.Show Notes0:00 Intro to The Genetics Podcast01:27 Welcome to Angela and how she joined Alzheimer Europe06:06 The biggest priorities and areas of focus for dementia and Alzheimer’s Disease (AD) research10:10 Biomarkers for dementia and how early in disease development they can be utilized12:40 The heterogeneity of dementia and AD and current understanding of subtypes and treatment journeys17:20 The challenges of diagnosis, early identifiers, and the integration of genetics18:53 Angela’s view on the latest breakthrough therapies22:50 Partnering in and supporting dementia research efforts across 30+ European countries29:15 Reimbursement frameworks and shared regulations across different countries33:40 Angela’s thoughts on the near future of gene therapies for AD and dementia38:04 Why Angela spent 50 hours travelling the length of Australia by bus41:26 Closing remarksFind out moreAlzheimer EuropePlease consider rating and reviewing us on your chosen podcast listening platform!
• 
  EP 241: The hard-won lessons behind Encoded Therapeutics’ Dravet syndrome gene therapy with Salvador Rico [Re-run] 28.05.2026 45min

  This week on The Genetics Podcast, Patrick is joined by Salvador Rico, Chief Medical Officer at Encoded Therapeutics. With Encoded’s Dravet syndrome gene therapy program recently reaching major clinical and regulatory milestones, we’re revisiting this conversation on Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and the fundamental challenges and exciting advances shaping the future of genetic medicine.Show Notes0:00 Intro to The Genetics Podcast01:27 Welcome to Salvador and how he became involved in drug development11:29 Frustrations and rewards of the genetics field14:27 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)20:13 Risk of liver issues in gene therapy trials and attempts to mitigate them24:50 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team27:50 Steps towards therapeutic targeting of gene regulatory elements 30:32 Advantages of different methods for drug delivery 32:59 DNA- versus RNA-based therapy 35:24 Insights from approaches in other fields, including psychiatry37:03 Considerations for using natural history studies41:00 Expectations and goals for Encoded Therapeutics’ current and upcoming studies43:45 Closing remarksFind out moreEncoded TherapeuticsNew clinical data
• 
  EP 240: Hijacking DNA repair machinery to treat Huntington’s disease with Vincent Dion of the UKDRI 21.05.2026 43min

  This week on The Genetics Podcast, Patrick is joined by Dr. Vincent Dion, Group Leader at the UK Dementia Research Institute at Cardiff University. They discuss how repeat expansions drive Huntington’s disease and other neurological disorders, why DNA repair can sometimes worsen these mutations over time, and how CRISPR nickase editing could offer a new way to shrink disease-causing repeats rather than simply silence them.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Vincent01:45 Working on origins-of-life chemistry in Stanley Miller’s lab03:56 Vincent’s path to genetics 06:00 How somatic repeat expansion drives Huntington’s disease 09:40 Therapeutic strategies for Huntington’s disease15:29 Using gene editing to shrink repeat expansions18:31 Optimizing CRISPR nickase delivery and expression for repeat expansion editing25:15 Moving gene editing from academic research toward a first-in-human trial27:31 Clinical trial challenges for Huntington’s gene therapies and uniQure’s early data30:47 Epigenetic regulation of repeat instability in neurodegenerative disease33:14 How basic science breakthroughs like CRISPR become transformative biology tools34:55 How academic couples navigate the two-body problem when building research careers39:39 Developing biomarkers to measure whether DNA-targeting therapies are working42:17 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform!
• 
  EP 239: What long-read sequencing reveals about Alzheimer’s and ALS with Paul Valdmanis of the University of Washington 14.05.2026 40min

  This week on The Genetics Podcast, Patrick is joined by Dr. Paul Valdmanis, Associate Professor at the University of Washington. They discuss the impact of APOE4 on risk in Alzheimer’s disease, how long-read sequencing is uncovering hidden genetic variation in Alzheimer’s and ALS, and what rare variants and cryptic splicing can teach us about neurodegeneration.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Paul01:40 Long-read sequencing and ancestry-specific APOE4 risk in Alzheimer’s disease04:20 Key findings from Paul’s study on a protective APOE4-linked variant in Alzheimer’s disease10:58 What rare PSEN1 and PSEN2 variants reveal about Alzheimer’s disease biology14:38 Disease-specific genetic mechanisms in ALS versus Alzheimer’s17:14 Precision therapies for neurodegenerative disease18:35 Choosing therapeutic targets in the neurodegenerative disease cascade20:21 Landscape of ALS and Alzheimer’s therapies 23:48 Lessons from liver-directed gene therapy on microRNA toxicity, cancer risk, and brain delivery challenges29:12 Using long-read sequencing to uncover tandem repeat expansions missed by conventional genomics33:26 Findings from a study of long-read sequencing on ancient genomes38:06 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_linkFind out more:APOE studyAncestry study
• 
  EP 238: Uncovering epistatic interactions in complex disease with machine learning with Bin Yu of UC Berkeley 07.05.2026 39min

  This week on The Genetics Podcast, Patrick is joined by Dr. Bin Yu, CDSS Chancellor’s Distinguished Professor at UC Berkeley. They discuss how different statistical approaches, from linear models to random forests, can be used to study complex genetic traits, recent findings on epistasis in cardiomyopathy, and how improving robustness and reproducibility can lead to more reliable scientific conclusions.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Bin01:47 Linear models as the foundation of genetic analysis05:34 Using random forests and stability to identify gene–gene interactions beyond linear models11:05 How iterative feature weighting in random forests improves detection of gene interactions13:10 Using GWAS to prioritize features in high-dimensional genetic data15:06 Applying stable interaction models to hypertrophic cardiomyopathy in UK Biobank20:47 Biological insights from gene–gene interactions in cardiomyopathy and evidence for indirect epistasis23:25 Scaling discovery of epistatic interactions with better data and integrated experimental validation27:21 The predictability, computability, and stability (PCS) framework for data science30:06 How Bin’s early life during the Chinese Cultural Revolution shaped her 32:54 Balancing AI-driven productivity with human reasoning and scientific thinking35:23 Developing the ability to read people through observation, listening, and real-world interaction38:03 Closing remarksFind out more:Epistasis in cardiac hypertrophy studyhttps://vdsbook.com/
• 
  EP 237: How genetics and environment shape neurodegeneration in Alzheimer's and Parkinson's with Sarah Marzi of King’s College London 30.04.2026 39min

  This week on The Genetics Podcast, Patrick is joined by Dr. Sarah Marzi, Senior Lecturer at King's College London and group leader at the UK Dementia Research Institute. They discuss the impact of genes and environment on neurodegenerative disease, including: how APOE genotype shapes microglial function, how cell type-specific epigenomics of postmortem brain tissue is revealing the role of microglia and oligodendrocytes in Alzheimer's disease, and how pesticide exposure drives selective dopaminergic neuron loss and neuroinflammation in Parkinson's.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Sarah02:13 Environmental contributions to Parkinson’s disease and ALS05:01 The role of microglia in Alzheimer’s disease and findings from a study on APOE variants in a mouse model12:50 APOE4 effects on lipid accumulation, microglial activation, and vitamin D receptor signaling 14:20 Building a multi-omic atlas of the Alzheimer’s brain18:01 Overview of the pathological cascade of events in the Alzheimer’s brain20:31 Anti-amyloid therapies, early intervention, and combination treatment strategies 22:24 Rotenone exposure and microglial immune activation in Parkinson’s disease29:24 Dopaminergic neuron vulnerability to pesticide exposure and mitochondrial dysfunction 31:04 Familial Parkinson’s genes, polygenic Alzheimer’s risk, and genetically targeted clinical trials33:13 Polygenic risk and microglial cell state regulation in Alzheimer’s disease34:13 Defining cell states in single cell RNA sequencing35:30 Oligodendrocyte epigenetic and transcriptional changes in Alzheimer’s disease37:23 Sarah’s most memorable hiking adventures38:58 Closing remarksFind out more:Alzheimer’s APOE microglia xenotransplantation studyRotenone exposure Parkinson’s study
• 
  EP 236: Fixing access and design in rare disease drug development: Insights from experts and patient advocates 23.04.2026 44min

  This week on The Genetics Podcast, Patrick is joined by Lindsey Wahlstrom, Co-Founder and Chief Momatologist of Rona’s FUN LAB, Jimi Olaghere, sickle cell disease patient advocate and early CRISPR gene therapy trial participant, and Rachel Smith, Vice President and Head of Rare and Genetic Diseases at Parexel. They discuss the realities of developing and delivering advanced therapies in rare disease, how funding models, regulation, and trial design shape access and outcomes, and why embedding patient experience early is critical to building therapies that are not only effective but scalable, accessible, and meaningful for patients and families.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to guests and what Rare Disease Day means to them08:09 Balancing hope with funding, pricing, and access in advanced therapies11:48 Why patient access must be built into drug development from day one14:20 Patient engagement, community readiness, and the realities of trial participation17:49 Why early patient input is still inconsistent and often treated as a checkbox23:20 Designing trials around what actually matters to patients and families26:53 Navigating regulators, payers, and trial design constraints in rare disease therapies36:02 Redefining success in gene therapy around access, scalability, and real patient benefit43:27 Closing remarks
• 
  EP 235: Inside Alzheimer’s disease: Blood biomarkers and predicting symptoms with Suzanne Schindler of Washington University 16.04.2026 39min

  This week on The Genetics Podcast, Patrick is joined by Dr. Suzanne Schindler, Associate Professor of Neurology at Washington University in St. Louis. They discuss how blood-based biomarkers like p-tau217 are transforming our ability to detect and stage Alzheimer’s disease, how “clock models” can estimate when symptoms may begin, and how combining biomarkers with clinical phenotyping could improve trial design, prognosis, and patient care.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Suzanne01:35 Neurobiology of Alzheimer’s disease and how it differs from dementia06:22 Presymptomatic changes to phosphorylated tau (p-tau) in the brain07:36 The role of the APOE gene in Alzheimer’s09:07 Differences in neuropathology in women vs men with Alzheimer’s10:19 Rare cases where amyloid and tau pathology do not align in Alzheimer’s12:37 Using plasma p-tau217 trajectories to estimate when Alzheimer’s symptoms may begin17:30 Using p-tau217 to select clinical trial participants and predict progression timelines20:59 Overview of therapeutic strategies in Alzheimer’s disease24:24 Why APOE effects may not appear in p-tau217 measurements26:30 Combining biomarkers and clinical phenotyping to understand disease progression in Alzheimer’s30:08 Early-onset vs late-onset Alzheimer’s and differences in clinical presentation31:45 Expanding beyond p-tau217 to proteomics and multimodal biomarkers for predicting symptoms33:52 MTBR-tau243 as a more specific marker of tau pathology and Alzheimer’s symptoms37:31 Expanding biomarkers beyond Alzheimer’s and bringing blood tests into clinical practice38:49 Closing remarksFind out more:Phosphorylated tau217 studyMTBR-tau243 study
• 
  EP 234: Inside rare disease trial operations: The role of CROs in an evolving landscape with Derek Ansel of Worldwide Clinical Trials 09.04.2026 42min

  This week on The Genetics Podcast, Patrick is joined by Derek Ansel, Global Vice President and Therapeutic Strategy Lead for Rare Disease and Oncology at Worldwide Clinical Trials. They discuss how contract research organizations design and run rare disease trials, the challenges of selecting endpoints and patient populations, and how emerging approaches like n-of-1 therapies, regulatory flexibility, and AI are reshaping clinical development.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Derek01:38 The role of Contract Research Organizations (CROs) in clinical development02:41 Why endpoints are the hardest problem in rare disease trial design05:24 How Derek’s team chooses and operationalizes endpoints in rare disease trials08:14 Balancing patient selection, signal detection, and trial feasibility in rare disease11:55 How the FDA’s new guidance for personalized therapies could accelerate rare disease drug development14:20 Patient engagement, genetic counseling, and decision-making in genetic trials19:30 Patient and clinician dynamics in genetic subtypes of common disease23:05 What needs to change to make n-of-1 therapies scalable and accessible26:12 Where AI is delivering real impact in clinical trials today and where it is heading31:24 Operational bottlenecks, risk tolerance, and the limits of AI adoption in clinical trials34:55 Derek’s path from early clinical research roles to genetic counseling and rare disease drug development38:51 Key areas driving progress in rare disease over the next five years41:42 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform! 
• 
  EP 233: Unlocking early detection in liver disease with data and genetics with Tim Jobson of Predictive Health Intelligence 02.04.2026 33min

  This week on The Genetics Podcast, Patrick is joined by Dr. Tim Jobson, consultant physician and gastroenterologist at Somerset NHS Foundation Trust and Medical Director of Predictive Health Intelligence (PHI). They discuss the rising burden of metabolic liver disease and how routine clinical data can be used to detect disease earlier and prevent late-stage presentation. They also discuss the LiveWell study, a collaboration between Sano Genetics and PHI, and what it reveals about layering genetics and other data types to improve risk stratification and clinical trial recruitment. Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Tim01:50 The rise of metabolic liver disease and worsening mortality trends04:35 Motivation and goals behind the Somerset Liver Improvement Program to address late diagnosis09:13 Where genetics is already used in liver disease and where it’s still emerging13:17 Current tools for staging liver disease and the challenge of predicting progression at scale18:48 How the LiveWell study could improve risk prediction and reshape trial recruitment in liver disease23:58 Applying longitudinal risk detection beyond liver disease to cardiometabolic and other chronic conditions26:35 Using subtle changes in routine blood tests to identify cancer risk earlier28:09 Using existing health data to drive earlier intervention and maximize patient impact30:05 Expanding beyond liver disease, scaling early detection, and advancing precision medicine32:18 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform! 
• 
  EP 232: How ethics and law shape reproductive technology and AI in medicine with Glenn Cohen of Harvard Law School 26.03.2026 23min

  This week on The Genetics Podcast, Patrick is joined by Dr. Glenn Cohen, Professor at Harvard Law School. They discuss the evolving legal and ethical landscape of reproductive genetics, why regulation in areas like embryo selection remains limited, and questions arising around the use of AI in healthcare.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Glenn01:35 An overview of the courses Glenn teaches at Harvard Law School02:29 Glenn’s areas of expertise across biomedical ethics03:20 Ethical considerations around reproductive medicine and polygenic risk scores10:37 Regulatory uncertainty and limited oversight in reproductive genetics13:18 Liability, regulation, and real-world implementation challenges for AI in healthcare14:52 Risk–benefit framework for evaluating AI use in clinical settings17:19 Glenn’s experience contributing to landmark Supreme Court cases in biotechnology and health law20:09 Glenn’s perspective on mitochondrial replacement and its regulatory divide between the UK and US22:20 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform!