This week on The Genetics Podcast, Patrick is joined by Dr. Beth Shapiro, Chief Science Officer at Colossal Biosciences. They discuss her path into ancient DNA and evolutionary genetics, how advances in genome engineering are reshaping de-extinction and conservation science, and why restoring lost ecological functions could transform the future of biodiversity.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Beth

01:43 Beth’s path from journalism to ancient DNA research

04:46 Beth’s first project on American bison and near extinction

08:26 How Beth worked on a dodo sample at Oxford and what ancient DNA could reveal

11:09 How de-extinction entered the field and why resurrecting species became a scientific goal

14:54 Why de-extinction efforts could strengthen ecosystems and accelerate species conservation

18:33 How cloning a mammoth works and why genome engineering replaces traditional cloning

25:05 Understanding the genome of a woolly mammoth

28:06 What functional de-extinction means in practice

30:55 Genetic clues behind the woolly mammoth’s coat

33:25 The technical hurdles behind de-extinction

38:23 Building a stepwise path to de-extinction through near-term conservation tools

39:36 Ethics risk management and working with local and Indigenous communities in de-extinction projects

44:59 Scientific and technological breakthroughs needed over the next decade to make de-extinction and biodiversity preservation viable

49:20 Closing remarks

Find out more:

Colossal Biosciences (https://colossal.com/)

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This week on The Genetics Podcast, Patrick is joined by Dr. Graham Dempsey, CEO and co-founder of Quiver Bioscience. They discuss Graham’s path into neuroscience and biotech, how Quiver is building genetically validated programs in pain and neurodevelopmental disorders, and what recent advances in RNA-based therapies could mean for the future of neurological disease.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Graham

01:29 The motivations and mission driving Quiver Bioscience

04:34 Quiver’s approach to targeting the brain for neurological disease

06:58 Nav1.7 as a lead pain program and the mechanisms of pain signaling

12:11 Patient population and unmet need in chronic pain 

13:37 The Dup15q neurodevelopmental program and recent clinical progress

17:29 How the company chooses which diseases to pursue and why genetically validated pain and epilepsy programs lead the pipeline

20:10 Modeling pain in a dish and how cellular electrophysiology reveals disease and drug effects

27:42 Lessons from building a biotech company

29:53 Today’s biotech climate and why Graham is optimistic 

31:56 Emerging delivery technologies that could unlock the next wave of oligonucleotide therapies

33:51 How molecular shuttles cross the blood–brain barrier and the advantage of a dual target approach

37:05 Graham’s path from aspiring sports medicine doctor to building light-based platforms in neuroscience

40:15 Graham’s early exposure to biotech leadership and a formative encounter with Roy Vagelos

42:09 Closing remarks

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Find out more:

• Quiver Bioscience (https://www.quiverbioscience.com/)

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 Podcast

01:00 Welcome to Arabella 

01:30 Background and structure of the Genetic Frontotemporal Initiative (GENFI) consortium

02:48 Scale of the GENFI cohort and the breadth of longitudinal data collected

06:06 Clinical signs and progression of frontotemporal dementia (FTD) 

10:08 How genetic variants map onto different clinical forms of frontotemporal dementia

12:11 Biomarkers in genetic FTD and the challenge of separating neurodegeneration from lifelong brain differences

19:36 Mutation-specific cortical microstructure patterns in FTD and what MRI reveals at the earliest stages

23:04 Why combining genetics imaging fluid and digital biomarkers is essential for early detection and trials in FTD

25:39 How the GENFI consortium is run across more than 50 sites worldwide

30:42 How urgency and unmet need drive strong collaboration in the FTD community

33:11 Promising developments in FTD therapeutics

36:39 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Find 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 Podcast

00:59 Welcome to Krishna 

01:40 How a gap year in India deepened Krishna’s interest in health and population genomics

06:16 Key advances that reshaped cardiovascular genomics from rare variants to polygenic risk

09:18 Where cardiovascular genomics stands today across coronary disease, cardiomyopathies, and arrhythmias

14:25 Factors that make heart failure challenging for genomics 

17:32 How monogenic variants and polygenic load shape risk in dilated cardiomyopathy

23:03 What genetics reveals about the roots of heart failure and why precise phenotypes matter

26:12 Using genetic risk to guide earlier treatment and prevent progression to heart failure

30:37 Subclinical markers and imaging strategies to track progression toward heart failure

32:04 Key research findings on an ancestry-specific genetic driver of dilated cardiomyopathy

41:21 Genetic signals highlighting the role of inflammation in coronary artery disease

43:11 Building a clinical genomics engine that connects discovery to cardiovascular care

47:14 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Find 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 Podcast

01:00 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 diagnosis

06:18 Insights from early genomic newborn screening pilots

11:37 The clinical impact and economic benefits of newborn genomic screening

14:27 How GeneDx combines data, AI, and clinical expertise to improve genomic interpretation

17:44 A vision for a lifelong genomic passport and how it could guide care across every stage of life

20:42 How GeneDx Infinity is unlocking new therapeutic possibilities in genetically linked autism

22:48 How advocacy communities guide patient identification and connect families to opportunities

26:00 Lessons from 23 years at Microsoft that Lisa now applies to leading GeneDx

30:39 How Truveta emerged from the COVID crisis to build a shared-data platform for population-scale health insights

32:13 What excites Lisa most about leading GeneDx and where she sees the biggest opportunities ahead

34:59 Closing remarks

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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 Podcast

00:59 Welcome to Jeffrey

01:33 Early discovery of the dystrophin gene and how it shaped Duchenne muscular dystrophy (DMD) research

09:07 Efforts to map dystrophin and develop practical diagnostic techniques

12:04 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 strategy

27:23 Current successes and safety challenges in systemic AAV gene therapy for neuromuscular disease

34:44 Prospects and limitations of gene editing for Duchenne and emerging alternatives to AAV micro-dystrophin

44:57 Closing remarks

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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 Podcast

01:00 Welcome to Rachel

01:35 Background of Armatus Bio and the mechanism behind its vectorized RNAi platform

05:31 Advantages of vectorized RNAi over conventional RNAi approaches

08:07 How microRNAs work and how engineered versions enable highly specific gene silencing

10:28 Current preclinical progress at Armatus and next steps toward first-in-human trials

14:06 Lessons on making smart risk decisions in rare disease drug development

17:26 Reflections on two decades of progress, setbacks, and realities in gene therapy

22:07 Hemophilia as a case study in gene therapy missteps and overlooked patient and market realities

25:21 Challenges around product purity and the need for financial innovation

29:23 Why AAV purity is so difficult to achieve and where pre-competitive collaboration could drive improvement

33:32 Rachel’s path from veterinary medicine to gene therapy through a family genetic diagnosis

35:58 Founding the Stop ALD Foundation and advancing lentiviral gene therapy into first-in-human use

39:58 The future potential of vectorized RNAi 

42:00 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: 

This week on The Genetics Podcast, Patrick is joined by Slavé Petrovski, Vice President of the Center for Genomics Research at AstraZeneca. They discuss how AstraZeneca is scaling population genomics through massive biobank collaborations, developing AI models for early disease prediction, and pioneering sustainable “green” algorithms to reduce the environmental footprint of large-scale genomic research.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Slavé

02:09 Slavé’s career path from business information systems to genomics

04:33 How Slavé decided to move from academia to industry

07:52 Scaling and diversifying biobank partnerships to unlock new genetic insights

12:29 Translating biobank data into predictive and preventive medicine

15:14 Discovering protective genetic variants through global biobank studies

19:13 Leveraging population genetics to identify and validate protective drug targets

23:52 Developing an AI tool (MILTON) for integrating multi-omic and clinical data for early disease prediction

28:12 Redefining clinical trials in a presymptomatic and predictive medicine era

30:49 AstraZeneca’s efforts to make large-scale genomics computing sustainable through green algorithm innovation

39:05 AstraZeneca’s open science strategy and global impact of its shared genomics tools

42:10 Fostering critical thinking and avoiding groupthink in large-scale genomics research

45:30 Looking ahead to the next decade of genomics and precision healthcare

50:01 Closing remarks

Find out more

• MILTON (https://www.astrazeneca.com/r-d/our-technologies/machine-learning-drug-discovery.html)

• PheWAS Portal (https://azphewas.com/)

• Upcoming webcast with deep dive into MILTON & PheWAS (https://www.nature.com/articles/d44224-025-00033-7)

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 Dr. Ellen Reisinger, Professor and group leader at the University of Tübingen. They discuss her journey into hearing loss research, why otoferlin has become a leading target for gene therapy, and the emerging science shaping the next generation of treatments.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Ellen

01:52 Ellen’s career path that coincidentally led to her work on otoferlin-related hearing loss

03:22 Mechanism and advantages of the dual adenoassociated virus (AAV) system 

05:35 The genetic landscape of early-onset hearing loss and why otoferlin stands out

07:42 Why otoferlin-related deafness is an ideal target for postnatal gene therapy development

09:53 Potential next gene therapy targets beyond otoferlin and associated challenges

13:13 Carrier and newborn screening as approaches to preventing hereditary hearing loss

14:37 How far the field is from prenatal gene therapy and why it remains unlikely in the near term

16:07 Exploring gene-agnostic and protective approaches to prevent or slow hearing loss

18:22 How genetics and environment interact in age-related hearing loss

20:00 Current research focus of Ellen’s group on degenerative hearing loss genes and uncovering cell death mechanisms

22:05 Using mouse models and human organoids to study hearing loss mechanisms

23:42 Emerging gene editing approaches 

25:20 Ellen’s research journey from biochemistry to leading gene therapy research in hearing loss 

27:54 Unanswered questions about how inner hair cells release neurotransmitters

29:21 Comparing outcomes of gene therapy and cochlear implants for hearing restoration and differences across languages

34:20 Closing remarks

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: 

This week on The Genetics Podcast, Patrick is joined by BridgeBio’s Ananth Sridhar, Chief Operating Officer of Cardiorenal Programs, and Sun-Gou Ji, Vice President of Computational Genomics. They discuss the hub-and-spoke model for de-risking and accelerating rare disease drug development, the role of human genetics in target discovery, lessons from their autosomal dominant hypocalcemia type 1 (ADH1) program, and how portfolio design and predictive genomics are shaping the future of precision medicine.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Ananth & Sun-Gou

01:57 How BridgeBio’s hub-and-spoke model de-risks and accelerates rare disease drug development

06:45 How programs move from the hub to the spokes in target discovery and development

09:10 Translating a target into a therapy for autosomal dominant hypocalcemia type 1 (ADH1)

12:28 Challenges in ADH1 drug development and using population genetics to identify patients with gain-of-function variants

18:08 Under-diagnosis and incomplete penetrance in rare disease and quantifying genetic versus phenotypic prevalence

20:52 Balancing first-in-class innovation with risk management in rare disease drug development

24:24 Evaluating rare disease programs using risk-adjusted net present value (NPV) instead of peak sales

27:20 Key factors that can make rare disease programs faster and cheaper to develop, and why modality agnosticism is important

32:00 Sun-Gou’s experience in computational genetics and building data-driven infrastructure for discovery

36:44 Ananth’s lessons from Regeneron and applying patient-centered principles to rare disease drug development

39:00 Sun-Gou on the power of newborn sequencing and personal lessons from early diagnosis

43:36 Ananth’s views on making predictive medicine more personal and human-centered

44:51 Closing remarks

Find out more

• BridgeBio (https://bridgebio.com/unlocking-rare-diseases-medicine)

• Hub-and-spoke model (https://www.youtube.com/watch?v=gRURL49QsX4)

• ADH1 publication (https://www.cell.com/ajhg/fulltext/S0002-9297(25)00244-7)

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