The Genetics Podcast

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

Helen O’Neill, a molecular geneticist and founder of Hertility Health, chats about her unique insights into genetics sparked by being an identical twin. She shares her firsthand experience during the CRISPR baby controversy and discusses the persistent public skepticism around gene editing. O’Neill highlights her research on embryo viability through genetic screening and the potential for newborn genome sequencing to revolutionize early diagnosis. Additionally, she reveals how Hertility Health is transforming women’s access to fertility care.

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