The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Dr. Arabella Bouzigues, Coordinator of the Genetic Frontotemporal Dementia Initiative (GENFI) and postdoctoral researcher. They discuss the scale and structure of GENFI as a global collaboration and what longitudinal data is revealing about genetics and biomarkers in frontotemporal dementia.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Arabella 01:30 Background and structure of the Genetic Frontotemporal Initiative (GENFI) consortium02:48 Scale of the GENFI cohort and the breadth of longitudinal data collected06:06 Clinical signs and progression of frontotemporal dementia (FTD) 10:08 How genetic variants map onto different clinical forms of frontotemporal dementia12:11 Biomarkers in genetic FTD and the challenge of separating neurodegeneration from lifelong brain differences19:36 Mutation-specific cortical microstructure patterns in FTD and what MRI reveals at the earliest stages23:04 Why combining genetics imaging fluid and digital biomarkers is essential for early detection and trials in FTD25:39 How the GENFI consortium is run across more than 50 sites worldwide30:42 How urgency and unmet need drive strong collaboration in the FTD community33:11 Promising developments in FTD therapeutics36:39 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: GENFI (https://www.genfi.org/)

This week on The Genetics Podcast, Patrick is joined by Dr. Krishna Aragam, Section Head of Cardiovascular Genomics and Precision Medicine at the Cleveland Clinic. They discuss Krishna’s early experiences in population research and how they shaped his approach to genetics, the major discoveries transforming cardiovascular genomics from monogenic to polygenic risk, and how new insights into heart failure and population-specific variants are redefining the future of clinical care.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Krishna 01:40 How a gap year in India deepened Krishna’s interest in health and population genomics06:16 Key advances that reshaped cardiovascular genomics from rare variants to polygenic risk09:18 Where cardiovascular genomics stands today across coronary disease, cardiomyopathies, and arrhythmias14:25 Factors that make heart failure challenging for genomics 17:32 How monogenic variants and polygenic load shape risk in dilated cardiomyopathy23:03 What genetics reveals about the roots of heart failure and why precise phenotypes matter26:12 Using genetic risk to guide earlier treatment and prevent progression to heart failure30:37 Subclinical markers and imaging strategies to track progression toward heart failure32:04 Key research findings on an ancestry-specific genetic driver of dilated cardiomyopathy41:21 Genetic signals highlighting the role of inflammation in coronary artery disease43:11 Building a clinical genomics engine that connects discovery to cardiovascular care47:14 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: Genetic variants underlying DCM: https://pmc.ncbi.nlm.nih.gov/articles/PMC11631752/ Ancestry-specific CD36 study: https://www.nature.com/articles/s41588-025-02372-2

Summary: This week on The Genetics Podcast, Patrick is joined by Lisa Gurry, Chief Business Officer of GeneDx. They discuss her path from two decades at Microsoft to leading one of the most influential genomics companies, GeneDx’s mission to deliver the fastest rare disease diagnoses, and how large-scale data, newborn screening, and AI are shaping the future of precision medicine.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Lisa and her career path leading to joining GeneDx  03:27 The core components of GeneDx and how they drive early rare disease diagnosis06:18 Insights from early genomic newborn screening pilots11:37 The clinical impact and economic benefits of newborn genomic screening14:27 How GeneDx combines data, AI, and clinical expertise to improve genomic interpretation17:44 A vision for a lifelong genomic passport and how it could guide care across every stage of life20:42 How GeneDx Infinity is unlocking new therapeutic possibilities in genetically linked autism22:48 How advocacy communities guide patient identification and connect families to opportunities26:00 Lessons from 23 years at Microsoft that Lisa now applies to leading GeneDx30:39 How Truveta emerged from the COVID crisis to build a shared-data platform for population-scale health insights32:13 What excites Lisa most about leading GeneDx and where she sees the biggest opportunities ahead34:59 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

 This week on The Genetics Podcast, Patrick is joined by Dr. Jeffrey Chamberlain, Professor at the University of Washington School of Medicine, co-founder of Kinea Bio, and Director of the Muscular Dystrophy Cooperative Research Center of Seattle. They discuss the early breakthroughs that revealed the structure and function of the dystrophin gene, how those insights led to the creation of micro-dystrophin and systemic AAV delivery in Duchenne, and the major scientific and clinical challenges the field must now solve.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Jeffrey01:33 Early discovery of the dystrophin gene and how it shaped Duchenne muscular dystrophy (DMD) research09:07 Efforts to map dystrophin and develop practical diagnostic techniques12:04 How research in Jeffrey’s lab gradually led to the creation of micro-dystrophin 20:15 How micro-dystrophin and AAV delivery converged into a viable systemic gene therapy strategy27:23 Current successes and safety challenges in systemic AAV gene therapy for neuromuscular disease34:44 Prospects and limitations of gene editing for Duchenne and emerging alternatives to AAV micro-dystrophin44:57 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 Dr. Rachel Salzman, CEO of Armatus Bio. They discuss the promise of vectorized RNAi for autosomal dominant diseases, the key scientific and clinical hurdles in gene therapy, and Rachel’s lessons from two decades in the field.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Rachel01:35 Background of Armatus Bio and the mechanism behind its vectorized RNAi platform05:31 Advantages of vectorized RNAi over conventional RNAi approaches08:07 How microRNAs work and how engineered versions enable highly specific gene silencing10:28 Current preclinical progress at Armatus and next steps toward first-in-human trials14:06 Lessons on making smart risk decisions in rare disease drug development17:26 Reflections on two decades of progress, setbacks, and realities in gene therapy22:07 Hemophilia as a case study in gene therapy missteps and overlooked patient and market realities25:21 Challenges around product purity and the need for financial innovation29:23 Why AAV purity is so difficult to achieve and where pre-competitive collaboration could drive improvement33:32 Rachel’s path from veterinary medicine to gene therapy through a family genetic diagnosis35:58 Founding the Stop ALD Foundation and advancing lentiviral gene therapy into first-in-human use39:58 The future potential of vectorized RNAi 42:00 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