The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Samuli Ripatti, Director of the Institute for Molecular Medicine Finland (FIMM), Vice Director at HiLIFE, and Professor of Biometry at the University of Helsinki. They discuss Samuli’s research on lipid and cardiovascular genetics, how polygenic risk scores are moving into clinical care, and the power of the FinnGen biobank. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Samuli01:48 Samuli’s path from statistics to genetics at the beginning of a new era03:09 Remembering Leena Peltonen and the Human Genetics Summer School05:46 Samuli’s research in lipid and cardiovascular genetics and the power of collaboration09:14 Integrating polygenic risk scores into cardiovascular and breast cancer care14:52 Using medication history in FinnGen to uncover cardiometabolic genetics and predict treatment patterns18:50 The future of polygenic risk scores in predicting prognosis and guiding treatment21:21 The confounding effect of treatment in genetic studies23:14 Overview of FinnGen and its impact on genetics and drug discovery27:04 The next 5 years in proteomics and molecular profiling to move beyond associations29:56 Using polygenic risk scores in clinical trials31:41 Future directions, from refining phenotypes in large biobanks to piloting clinical applications of polygenic risk scores34:04 Scaling population biobanks versus deep phenotyping and why the future requires both35:29 Closing remarksFind out moreGenetic predictors of lifelong medication-use patterns in cardiometabolic diseases (https://www.nature.com/articles/s41591-022-02122-5)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Jonathan Marchini, Head of Statistical Genetics and Machine Learning at the Regeneron Genetics Center. They discuss Jonathan’s pioneering role in developing computational methods from the HapMap era through to today, how those innovations underpin large-scale imputation and analysis, and why exomes with imputation remain more powerful than whole genomes for discovery at Regeneron.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Jonathan01:47 Jonathan’s career path from teaching in rural Tanzania to genomics research at Oxford04:43 Lessons from the HapMap era and the birth of imputation08:30 Ongoing challenges with data sharing and usable tools 10:30 Handling massive genetic datasets at Regeneron and developing new computational methods to scale15:26 Key discoveries from the million-exome paper18:04 Pushing computational limits in meta-analysis 19:50 Polygenic risk scores in the clinic and their role in trial design23:38 Why Regeneron prioritizes exomes with imputation over whole genomes and what that means for discovery27:58 Where AI truly adds value in genomics and where simpler models still win32:27 Interpreting rare variants, the promise of protein models, and why better phenotyping is key35:31 Closing remarks and opportunities at RegeneronFind out moreRegeneron Genetics Center (https://www.regeneron.com/science/genetics-center)Million exome paper (https://www.nature.com/articles/s41586-024-07556-0)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Max Bronstein, CEO of Aviva Strategies. They discuss the shifting regulatory and political landscape shaping biotech, the realities of today’s drug development process, and why new incentives and flexible trial pathways are critical to advancing rare and ultra-rare disease therapies.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Max01:51 Regulatory shifts and FDA challenges under the new administration05:40 Overview of the regulatory process for therapeutic development and the push for patient-centered trials11:26 Challenges in drug development from regulatory gaps to shifting FDA priorities15:45 Unprecedented government turnover and its impact on biotech industry stability18:32 Status and significance of the pediatric priority review voucher program for rare and ultra-rare disease development22:02 How Congress uses “must-pass bills” to advance or block health policies25:17 Max’s role in creating Advanced Research Projects Agency for Health (ARPA-H) to drive high-risk innovation 30:02 How ARPA-H is funded 31:21 Adapting science policy to politics33:35 Breakthroughs in rare disease therapies and the policy frameworks needed to ensure access37:15 Lessons from the Orphan Drug Act and why new incentives are needed to make ultra-rare disease drug development viable39:23 The push for flexible rare disease trial pathways and the disconnect between FDA rhetoric and practice43:26 Closing remarks and a call to connect for patient organizations and rare disease parentsFind out moreAviva Strategies (https://www.avivastrategies.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Richard Wilson, Senior Vice President, Primary Focus Lead of Genetic Regulation at Astellas. They discuss where the gene therapy field stands today, diving into successes, persistent barriers, regulatory considerations, manufacturing strategies, and other reflections on important approaches to precision medicine drug development.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Richard01:33 Current wins and challenges in gene therapy 07:13 The need for more open non-competitive data sharing and a clearer pathway towards reimbursement and incentivization11:15 Building post-approval systems into the genomic medicine lifecycle14:47 Rethinking evidence standards in rare disease trials, and the global push for regulatory and reimbursement alignment20:28 Genetic medicine breakthroughs in central nervous system diseases22:25 The challenges of starting clinical development with an end in mind24:34 The need for careful analysis around endpoints, vector design, and delivery approaches29:33 Navigating regulatory hurdles when making mid-program changes to vectors or payloads31:16 Strategies for enhancing scalability and quality of gene therapy manufacturing 36:05 Exploring other delivery methods beyond AAV39:32 Getting ready for the Timmerman Traverse and raising nearly $1M for Life Science Cares43:48 A call to refocus on patients, partnership, and purpose in uncertain times45:55 Closing remarks Find out moreAstellas (https://www.astellas.com/)Timmerman Traverse fundraising for Life Science Cares (https://timmermantraverse.blackbaud-sites.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, we celebrate our 200th episode with a look back at some of the earliest episodes, particularly ones that foresaw major trends or went on to spark real-world impact. These include Eric Topol’s early predictions about AI in healthcare, Laurence Reid’s vision for gene therapy in hearing loss, Sir Rory Collins on the potential impact of the UK Biobank, Daphne Koller on uniting biology and machine learning, and Vineeta Agarwala on harnessing large datasets for drug discovery. Patrick adds updates and reflections on how these bold ideas have shaped the genomics and biotech landscape.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Overview of episode content and guests featured01:47 Eric Topol predicts the role of AI in healthcare in 201905:58 Patrick’s reflections on AI’s progress today and future potential06:57 Laurence Reid outlines Decibel Therapeutics’ gene therapy plans for otoferlin-related hearing loss 10:58 Patrick’s updates on Decibel’s success and acquisition by Regeneron 11:44 Sir Rory Collins on the creation and vision of the UK Biobank18:20 Patrick on the lasting impact of open science and the UK Biobank19:10 Daphne Koller on building insitro to fuse biology and machine learning 24:30 Patrick on the future of large-language models in biology25:55 Vineeta Agarwala on investing in large datasets for drug discovery32:24 Patrick on applying multi-omic data to rare disease research32:52 Closing remarksFind out moreThe Genetics Podcast is now on Instagram! Follow us for clips from recent episodes and release announcements (https://www.instagram.com/thegeneticspodcast/).Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Xin Jin, Associate Professor in the Department of Neuroscience at The Scripps Research Institute. They discuss how in vivo Perturb-seq enables scalable and high-resolution modeling of neurogenetic disorders like autism, how introducing mutations directly into living mouse brains reveals cell-type vulnerabilities and convergent pathways, and why this approach could transform therapeutic development by identifying shared mechanisms across diverse genetic mutations.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Xin 01:52 Overview of in vivo Perturb-seq05:10 Identifying de novo variants in autism spectrum disorder09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types13:04 Applying Perturb-seq to other brain diseases14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways22:35 Conservation of genes between mouse and human in the context of neurodevelopmental disease modeling 24:21 Impact of genetic discoveries on drug development by convergence onto common pathways 27:22 Xin’s early interest in science through her grandfather’s work in plant taxonomy and botany29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models 37:21 Closing remarksFind out moreJin lab (https://www.jin.scripps.edu/)In vivo Perturb-seq explainer video (https://vimeo.com/549737357)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Benny Sorensen, CEO of Hemab Therapeutics. They discuss how Hemab is reimagining clotting therapies by centering patient voices, how persistence and being “unreasonable” led to their first program, and the value of their multi-modality and collaborative approach.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Benny01:49 Reimagining blood clotting therapies by listening to lived experience and embracing the biotech revolution04:27 How persistence and patient voices sparked Hemab’s first drug development program07:13 Overview of Glanzmann Thrombasthenia (GT) and Hemab’s antibody-based approach10:09 Evolution of hemophilia treatment and neglected blood clotting disorders14:18 Genetic and gender considerations around bleeding disorders17:41 Hemab’s range of therapeutic modalities and the value of collaboration 21:00 Why deep domain expertise drives Hemab’s strategy and success22:55 Lessons from the drug development process24:16 Global insights into gender bias, health inequality, and bleeding disorder care26:46 Upcoming milestones at Hemab 29:52 Lessons from running natural history studies to capture the patient experience33:25 Redefining the patient journey through data34:40 How Benny’s experience at Alnylam Therapeutics shaped his “unreasonable” leadership38:16 Reflections on being a father and a CEO 40:38 Closing remarks and Benny’s commitment to thoughtful drug developmentFind out moreHemab Therapeutics (https://www.hemab.com/)Hemab trial register (https://shorturl.at/8AAQN) Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Heiko Runz, medical geneticist and VP of Neuroscience at insitro. They discuss Heiko’s path into therapeutic genetics, how collaboration and data integration across biobanks led to his discovery of a protective variant for age-related macular degeneration, and the role of cell-based models in drug discovery.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Heiko01:41 Heiko’s career path and how he became interested in medical genetics and therapeutic development05:49 Connecting the dots across biobanks for genetic discovery08:23 Heiko’s discovery of a potential gene target for age-related macular degeneration15:29 The challenge of biobank recontact and why it’s essential for follow-up studies18:57 The opportunity for smaller companies to follow up on large-scale genomic discoveries23:00 Advances in cell-based models for neuroscience drug discovery24:40 Heiko’s role in the development of tofersen for SOD1 ALS  28:50 Targeting TDP-43 in ALS through large-scale cell-based phenotyping and drug discovery30:36 Using cell-based phenotypes to functionally test disease mechanisms and validate variants33:58 The potential of AI for refining phenotypes and generating drug hypotheses36:47 Heiko’s advice to early career professionals interested in the field of genetics and drug discovery38:26 Closing remarks Find out moreinsitro (https://www.insitro.com), study on CFHR5 (https://www.nature.com/articles/s41467-025-61193-3)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Molly He, CEO and co-founder of Element Biosciences. They discuss the current landscape of sequencing technologies, Element’s innovative sequencing platform, and the potential of using in-sample multiomic profiling across different stages of drug discovery. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Molly01:42 Persistent barriers in precision medicine04:54 Limitations of multiomics technologies and the unique advantage of Element’s approach07:33 How Element started by inventing an ambitious sequencing instrument11:33 Overview of the chemistry behind Element’s sequencing technology14:41 Sequencing workflow of Element’s technology and technical advantages18:24 Sequencing inside cells and drug discovery insights from a study on tyrosine kinase inhibitor (TKI) resistance pathways25:57 Sequencing for CRISPR perturbation and direct genotype–phenotype linkage in the same cell27:33 Whole-transcriptome in situ sequencing and applications in patient samples29:19 Simplifying single-cell transcriptomics with direct in-sample sequencing30:31 Applying the single-cell spatial technology to different steps of the drug discovery process36:43 Competition in the sequencing industry and recent news about Illumina filing a patent infringement case against Element38:43 Lessons from building Element over eight years40:32 Insight into maintaining a cohesive culture as Element has multiplied in size and across countries42:06 The importance of input data quality for AI applications and excitement about the possibility of predicting biology45:40 Closing remarksFind out moreElement Biosciences (https://www.elementbiosciences.com/)Pre-print (https://www.biorxiv.org/content/10.1101/2025.05.06.652479v1)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by David Bumcrot, Chief Scientific Officer of CAMP4 Therapeutics. They discuss David’s involvement in the development of the breakthrough technologies in RNA interference and CRISPR, how CAMP4 is pioneering the use of regulatory RNAs to treat haploinsufficient diseases, and the complexities of gene regulation. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to David 01:57 David’s experiences at companies that developed RNA interference (RNAi) and CRISPR technologies04:05 Lessons from translating RNAi to the bedside 05:58 The scalable chemistry of RNA versus the complexity of gene editing07:48 Insight into the lack of rapid scalability and growth in gene therapy companies09:19 How CAMP4 is using regulatory RNAs to boost gene expression in haploinsufficient diseases13:01 Mapping and predicting the impact of specific regulatory RNAs on the expression of target genes15:05 Why regulatory RNAs open up new target space without needing new drug modalities16:27 How CAMP4 prioritizes certain diseases based on delivery feasibility and genetic evidence18:31 Understanding expression thresholds in haploinsufficiency and building confidence in therapeutic targets 20:29 Comparing different approaches for increasing gene expression22:39 Other therapeutic areas of focus for CAMP4, including urea cycle disorders and central nervous system (CNS) disorders25:47 Lessons from early clinical development and engaging regulators on novel targets27:47 Building high-resolution regulatory RNA maps beyond what public datasets can provide31:04 Considerations around the treatment window for SYNGAP132:40 The value of collaborative frameworks for rapid therapy development 35:20 Rethinking early safety assessment and global regulatory strategies for RNA therapies38:37 The importance of basic science, staying optimistic, and continuing to invest in biotech innovation40:18 Closing remarksFind out moreCAMP4 Therapeutics (https://www.camp4tx.com)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Melissa Haendel, Director of Translational Informatics and Precision Health and Professor at the University of North Carolina at Chapel Hill, and Phenotypic Lead at Alamya Health. They discuss the limitations of electronic health records for rare disease diagnostics, how patient self-reporting can enhance diagnosis, expanding access to genomic testing in underserved settings, and the challenges and promise of national-scale health data infrastructure. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Melissa02:05 Melissa’s career path, beginning with finding her first professorship on Craigslist04:24 The fundamentals of ontology and how it can help identify common molecular mechanisms across different rare diseases06:29 Why key rare disease details are missing from electronic health records (EHRs) and how ontologies and AI can help11:33 How patient self-reporting using layperson phenotypic terms was associated with strong diagnostic performance15:27 Why recognizing multi-system patterns is key for diagnosing rare conditions and how tools like pattern-based screening are improving outcomes17:41 How Alamya Health is expanding access to genomic diagnostics by building local lab infrastructure in underserved communities22:03 How Alamya’s single-test, AI-powered approach helps solve complex cases in underserved settings24:18 Rethinking the true cost of delayed diagnosis, from wasted testing to the societal and family burden26:10 What it takes to do national-scale health data research in the U.S. and a vision of real-world data as a public utility33:37 Opening up access to national EHR data for research through health data networks36:15 The gap between real-world data and clinical research and why improving data quality benefits both care and science38:34 A major upcoming milestone in bringing unified rare disease codes into US healthcare with the Mondo ontology41:22 Closing remarks Find out moreTIS Lab (https://tislab.org/), Alamya Health (https://www.alamyahealth.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Frank Gentile, Chief Executive Officer of Casma Therapeutics. They discuss the role of autophagy in neurodegenerative diseases, Casma’s work on therapies for Gaucher’s disease and Parkinson’s disease, and the challenges and opportunities in rare disease biotech.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Frank 02:00 Origin story for Casma Therapeutics and its therapeutic focus on autophagy04:51 Diseases in which autophagy is dysregulated07:46 The link between GBA1 and Parkinson’s, and why so many neurodegenerative diseases exhibit autophagy defects12:28 Findings from Casma Therapeutics’ preclinical studies and associated mechanisms16:46 Milestones and design of Casma Therapeutics’ upcoming clinical studies20:24 Well-characterized cohorts of GDPD patients from natural history studies21:55 Identifying alternative therapeutic targets involved in autophagy initiation that are mTOR independent24:46 The negative effects of broad inhibition of mTOR25:57 Advantages and disadvantages of using small molecule therapy versus broader gene therapy26:59 Frank’s experience in investment and his approach to risk29:15 Frank’s perspective on the current biotech climate and how investors view rare disease32:16 Extending lead candidate and portfolio strategy to other therapeutic applications 34:15 Partnering opportunities and future potential of the TRPML1 program across neurodegenerative diseases35:50 A potential link between autophagy pathways and longevity37:20 Closing remarksFind out moreCasma Therapeutics (https://www.casmatx.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Huma Qamar, Chief Medical Officer at Ocugen. They discuss her journey from arriving in the US with $88 in her pocket to leading gene therapy programs, Ocugen’s breakthrough in retinal disease, and how gene-agnostic therapies could transform treatment for conditions like retinitis pigmentosa.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Huma 01:40 How Huma arrived in the US from Pakistan with $88 and went on to do medical training and research at Yale and Harvard06:47 Huma’s approach to challenges throughout her journey and how networking helped boost her career09:30 Ocugen’s mission to develop therapies for retinal disease and recent successes, including obtaining pediatric breakthrough designation12:10 Technical advantages and disadvantages of Ocugen’s retinal gene therapy 15:18 Insights from Huma’s experience across gene therapy trials versus oncology trials 19:17 Clinical landscape and genetic mutations in retinitis pigmentosa and the advantage of Ocugen’s gene-agnostic and gene modifier platform23:17 Therapy mechanism of reactivating degenerating photoreceptors via master regulators  26:32 Clinical trial design and regulatory considerations29:15 Huma’s vision and hopes for retinal diseases over the next 5-10 years 30:20 Huma’s experience as an interpreter and dedication to supporting immigrants and refugees32:12 Closing remarks and Huma’s message to women and patientsFind out moreOcugen (https://ocugen.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Andres Moreno-Estrada, population geneticist and head of the Human Evolutionary Genomics Lab at LANGEBIO in Mexico. They discuss the creation and insights of the Mexican Biobank, the genetic diversity of Latin America, ancient human migration, and the role of locally-led research in shaping public health and scientific equity.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Andres 01:56 Andres’ motivation to pursue genetics03:01 How and why Andres established the Mexican biobank with genotyping of more than 6,000 people07:25 Surprising findings on ancestry and regional similarities from the Mexican biobank09:26 Links between Indigenous ancestry, BMI, and disease-related traits12:36 Reconstructing population history from the Mexican biobank20:16 Tracing a single ancient contact between South America and Polynesia through shared Indigenous DNA21:58 Collaborative genomics efforts across Latin America and the launch of a regional Human Cell Atlas 26:39 How biobanks can inform national health decisions and why prioritization is the missing link in Mexico32:10 Public health applications of genetic data and the need for local and regional biobanks35:17 How ancient DNA reveals early cultural mixing and the deep roots of Mexico’s Day of the Dead traditions39:12 Closing remarks and a call for support and investment in locally-led science across Latin America and beyondFind out moreMoreno Lab (http://www.morenolab.org/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Frank Gleeson, co-founder and CEO of Satellos. They discuss Satellos’ novel approach to treating Duchenne Muscular Dystrophy by targeting muscle stem cell regeneration, how this fills a critical therapeutic gap, and the promising results of their early clinical trials. They also touch on what it takes to advance drug development and secure funding in today’s biotech landscape.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Frank and the origin story for Satellos and its focus on muscle stem cell regeneration to treat Duchenne Muscular Dystrophy (DMD)14:03 Counteracting degeneration in DMD and associated mechanisms16:08 Current therapeutic focuses in DMD, including gene therapy and exon skipping to increase expression of dystrophin24:28 Satellos’ drug development strategy, safety-first design, and early clinical findings in adults with DMD35:54 The study design and number of patients for Satellos’ phase 2 trial40:12 Frank’s recommendations for how biotechs can raise funding in today’s climate 44:38 Advantages of Frank’s career path across business and venture capital to biotech46:52 Closing remarks  Find out moreSatellos (https://satellos.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Tim Spector, Professor of Genetic Epidemiology at King’s College London and co-founder of Zoe. They discuss surprising insights on heritability from decades of twin research, the profound impact of the microbiome on health and disease, and the effect of diet on the gut microbiome. Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Tim and his journey from clinical medicine to pioneering twin studies and uncovering the heritability of diseases and traits07:20 Exploring missing heritability and why twin studies and GWAS offer different answers10:37 What a global mega twin registry could reveal about epigenetics, environment, and disease13:40 Findings from a twin microbiome study and how that evolved into a new chapter in Tim’s research career16:50 The profound impact of the microbiome on health21:08 Evolution in microbiome research techniques, microbe-diet associations, and the need for longitudinal studies 27:00 Potential reasons why fecal transplant did not turn out to be as effective as predicted28:53 The importance of balance in the gut microbiome and how it can be involved in cancer and the drug response35:54 Barriers to translating microbiome science into healthcare  38:38 The impact of microplastics and ultra-processed foods on the microbiome 41:27 Moving away from diversity measures for evaluating the microbiome and towards a more comprehensive score metric44:36 Closing remarks with information on Tim’s upcoming book as well as Zoe products and appFind out moreZoe (https://zoe.com)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by Daniel Geschwind, Professor, Senior Associate Dean, and Associate Vice Chancellor of Precision Health at UCLA. They discuss the circuitous career path that led Daniel to building a biobank that provided the foundation for autism genetics, the complexity of the molecular and genetic aspects of autism, and how gene therapies could advance treatment. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Daniel and how he transitioned from being a chemistry teacher and consultant to an academic clinician05:51 How a year filming ski movies helped Daniel decide what he wanted to do after college07:29 How Daniel got started in autism research and established a biobank that built the foundation for autism genetics11:38 Our current understanding of autism on the molecular and genetic levels18:04 The spectrum nature of autism and how it correlates to molecular and genetic differences 25:13 The potential convergence of variants of autism on common pathways and corresponding therapeutics31:18 Evidence for the early developmental etiology of autism and the complexity of the genetic aspect35:56 The developmental window for gene therapies in autism and the need for concurrent training   38:41 Successes and barriers to data sharing and collaboration, and the importance of biobanks and functional mapping51:40 Developing computational tools for a network approach to transcriptomes55:28 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_link

Summary: This week on The Genetics Podcast, Patrick is joined by Helen O’Neill, molecular geneticist, founder of Hertility Health, and associate professor at University College London (UCL). They discuss how Helen’s experience as an identical twin sparked her interest in genetics, her firsthand account of the CRISPR baby controversy, and why stubborn perceptions and sensational headlines continue to cast a shadow over the gene editing field, despite major scientific progress.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Helen and an overview of her career path and how being an identical twin sparked her interest in genetics04:57 Technology shifts in embryonic and fetal biology over the span of Helen’s career06:44 Helen’s firsthand account and reflections on the 2018 CRISPR baby controversy11:56 Evolution of gene editing in the face of a stubborn perception of it15:17 Findings from Helen’s recent study on the impact of genetic screening on embryo viability and the case for genome editing in IVF patients20:09 The stalled progress of germline genome editing in the context of regulation and public opinion 24:08 How newborn genome sequencing could transform early diagnosis and reproductive decision-making26:13 The origin story for Hertility Health and how it’s transforming women’s access to fertility care32:14 The strong impact of personalized health recommendations 33:19 Challenges in using genetics to diagnose women’s health conditions and the vision for a longitudinal biobank35:54 Future directions in Helen’s work on women’s health and genome editing37:21 Closing remarks Find out moreHertility Health (https://hertilityhealth.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Giles Yeo, geneticist and author of Gene Eating: The Science of Obesity and the Truth About Dieting and Why Calories Don't Count: How We Got the Science of Weight Loss Wrong. Giles and Patrick discuss the genetic, neural, and evolutionary drivers of obesity, the advancements in safe and effective obesity drugs, and the narratives around calorie counting and ultra-processed foods.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Giles and an overview of recent advances in obesity treatment04:28 How incretin-based therapies such as GLP-1 receptor agonists have enhanced our understanding of obesity 06:46 Unexpected effects of GLP-1-based therapies on neurodegenerative disease and addiction09:39 Relative safety and potential side effects of GLP-1-based therapies11:18 The gap in genetic characterization of individuals with different responses to GLP-1-based treatment13:10 Competition and demand in the market for obesity drugs15:46 Targeting comorbidities and genetic and neural components of obesity 19:09 Evolutionary aspects of obesity and how modern world factors can increase risk24:26 The role of choice in dietary habits26:29 The spectrum of genetic influences on body weight29:50 Next frontiers in obesity research and opportunities from genetic advances32:52 The controversial premise of Giles’ second book on why calorie counting misses the point in improving diet and health37:43 Giles’ nuanced perspective on ultra-processed foods44:46 Future avenues for Giles’ research, including mapping genetics and neural circuits underlying obesity46:05 Giles’ writing process and plans to write a third book   48:55 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Madhuri Hegde, SVP and Chief Scientific Officer of Revvity. They discuss Revvity’s advances in ultra-rapid clinical-grade sequencing, opportunities, challenges, and global inequities in newborn screening, and the dilemma of resequencing versus long-term data storage.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Madhuri01:52 Rebranding Revvity as a healthcare company02:51 Advancements in sequencing and Revvity’s projects, including newborn screening tests and clinical ultra-rapid sequencing12:29 Opportunities and challenges for newborn sequencing and global inequity in access17:46 Price of sequencing and data storage versus resequencing considerations21:10 Complexities and nuances of genomic data interpretation23:28 Rethinking data portability and storage across the lifespan26:00 Understanding penetrance and population genetics through lifelong sequencing27:36 Scaling genetic counseling to match advancements and the potential value of chatbots32:45 The promise of proteomics and translating Olink data to the clinic 34:31 Implementing polygenic risk scores in clinical management  37:12 Transitioning from academia to industry and insights into product development38:37 Closing remarksFind out moreRevvity (https://www.revvity.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link