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 Podcast

00:58 Welcome to Frank 

02:00 Origin story for Casma Therapeutics and its therapeutic focus on autophagy

04:51 Diseases in which autophagy is dysregulated

07:46 The link between GBA1 and Parkinson’s, and why so many neurodegenerative diseases exhibit autophagy defects

12:28 Findings from Casma Therapeutics’ preclinical studies and associated mechanisms

16:46 Milestones and design of Casma Therapeutics’ upcoming clinical studies

20:24 Well-characterized cohorts of GDPD patients from natural history studies

21:55 Identifying alternative therapeutic targets involved in autophagy initiation that are mTOR independent

24:46 The negative effects of broad inhibition of mTOR

25:57 Advantages and disadvantages of using small molecule therapy versus broader gene therapy

26:59 Frank’s experience in investment and his approach to risk

29:15 Frank’s perspective on the current biotech climate and how investors view rare disease

32:16 Extending lead candidate and portfolio strategy to other therapeutic applications 

34:15 Partnering opportunities and future potential of the TRPML1 program across neurodegenerative diseases

35:50 A potential link between autophagy pathways and longevity

37:20 Closing remarks

Find out more

• Casma Therapeutics (https://www.casmatx.com/)

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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 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 Podcast

00:59 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 Harvard

06:47 Huma’s approach to challenges throughout her journey and how networking helped boost her career

09:30 Ocugen’s mission to develop therapies for retinal disease and recent successes, including obtaining pediatric breakthrough designation

12:10 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 platform

23:17 Therapy mechanism of reactivating degenerating photoreceptors via master regulators 

26:32 Clinical trial design and regulatory considerations

29:15 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 refugees

32:12 Closing remarks and Huma’s message to women and patients

Find out more

• Ocugen (https://ocugen.com/)

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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 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 Podcast

00:58 Welcome to Andres 

01:56 Andres’ motivation to pursue genetics

03:01 How and why Andres established the Mexican biobank with genotyping of more than 6,000 people

07:25 Surprising findings on ancestry and regional similarities from the Mexican biobank

09:26 Links between Indigenous ancestry, BMI, and disease-related traits

12:36 Reconstructing population history from the Mexican biobank

20:16 Tracing a single ancient contact between South America and Polynesia through shared Indigenous DNA

21:58 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 Mexico

32:10 Public health applications of genetic data and the need for local and regional biobanks

35:17 How ancient DNA reveals early cultural mixing and the deep roots of Mexico’s Day of the Dead traditions

39:12 Closing remarks and a call for support and investment in locally-led science across Latin America and beyond

Find out more

• Moreno Lab (http://www.morenolab.org/)

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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 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 Podcast

01:00 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 mechanisms

16:08 Current therapeutic focuses in DMD, including gene therapy and exon skipping to increase expression of dystrophin

24:28 Satellos’ drug development strategy, safety-first design, and early clinical findings in adults with DMD

35:54 The study design and number of patients for Satellos’ phase 2 trial

40:12 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 biotech

46:52 Closing remarks 

Find out more

• Satellos (https://satellos.com/)

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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 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 Podcast

00:58 Welcome to Tim and his journey from clinical medicine to pioneering twin studies and uncovering the heritability of diseases and traits

07:20 Exploring missing heritability and why twin studies and GWAS offer different answers

10:37 What a global mega twin registry could reveal about epigenetics, environment, and disease

13:40 Findings from a twin microbiome study and how that evolved into a new chapter in Tim’s research career

16:50 The profound impact of the microbiome on health

21:08 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 predicted

28:53 The importance of balance in the gut microbiome and how it can be involved in cancer and the drug response

35:54 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 metric

44:36 Closing remarks with information on Tim’s upcoming book as well as Zoe products and app

Find out more

• Zoe (https://zoe.com)

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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 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 Podcast

00:59 Welcome to Daniel and how he transitioned from being a chemistry teacher and consultant to an academic clinician

05:51 How a year filming ski movies helped Daniel decide what he wanted to do after college

07:29 How Daniel got started in autism research and established a biobank that built the foundation for autism genetics

11:38 Our current understanding of autism on the molecular and genetic levels

18:04 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 therapeutics

31:18 Evidence for the early developmental etiology of autism and the complexity of the genetic aspect

35:56 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 mapping

51:40 Developing computational tools for a network approach to transcriptomes

55:28 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 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 Podcast

00:59 Welcome to Helen and an overview of her career path and how being an identical twin sparked her interest in genetics

04:57 Technology shifts in embryonic and fetal biology over the span of Helen’s career

06:44 Helen’s firsthand account and reflections on the 2018 CRISPR baby controversy

11:56 Evolution of gene editing in the face of a stubborn perception of it

15:17 Findings from Helen’s recent study on the impact of genetic screening on embryo viability and the case for genome editing in IVF patients

20:09 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-making

26:13 The origin story for Hertility Health and how it’s transforming women’s access to fertility care

32:14 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 biobank

35:54 Future directions in Helen’s work on women’s health and genome editing

37:21 Closing remarks 

Find out more

• Hertility 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 Podcast

00:59 Welcome to Giles and an overview of recent advances in obesity treatment

04:28 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 addiction

09:39 Relative safety and potential side effects of GLP-1-based therapies

11:18 The gap in genetic characterization of individuals with different responses to GLP-1-based treatment

13:10 Competition and demand in the market for obesity drugs

15:46 Targeting comorbidities and genetic and neural components of obesity 

19:09 Evolutionary aspects of obesity and how modern world factors can increase risk

24:26 The role of choice in dietary habits

26:29 The spectrum of genetic influences on body weight

29:50 Next frontiers in obesity research and opportunities from genetic advances

32:52 The controversial premise of Giles’ second book on why calorie counting misses the point in improving diet and health

37:43 Giles’ nuanced perspective on ultra-processed foods

44:46 Future avenues for Giles’ research, including mapping genetics and neural circuits underlying obesity

46:05 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 Podcast

00:59 Welcome to Madhuri

01:52 Rebranding Revvity as a healthcare company

02:51 Advancements in sequencing and Revvity’s projects, including newborn screening tests and clinical ultra-rapid sequencing

12:29 Opportunities and challenges for newborn sequencing and global inequity in access

17:46 Price of sequencing and data storage versus resequencing considerations

21:10 Complexities and nuances of genomic data interpretation

23:28 Rethinking data portability and storage across the lifespan

26:00 Understanding penetrance and population genetics through lifelong sequencing

27:36 Scaling genetic counseling to match advancements and the potential value of chatbots

32:45 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 development

38:37 Closing remarks

Find out more

• Revvity (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

This week on The Genetics Podcast, Patrick is joined by Dr. Euan Ashley, Chair of the Department of Medicine at Stanford, founder of various biotech companies, and author of The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them. They discuss Euan’s groundbreaking work on ultra-rapid genome sequencing and how widespread sequencing, wearables, and AI could shape the future of preventive medicine and human performance.

Show Notes: 

00:00 Intro to The Genetics Podcast

01:00 Welcome to Euan

01:50 A pivotal case in Euan’s career involving diagnosing a newborn experiencing cardiac arrest

06:41 How Euan’s team worked towards a record of eight hours from clinical sample to diagnosis

10:05 Hurdles that need to be overcome before ultra-rapid sequencing workflows can be widely used in clinical settings

11:40 Considerations around widespread genetic screening in newborns

16:10 Weighing utility and uncertainty in genetic testing for disease

19:17 Steps to a future where widespread genetic testing is economically viable 

23:54 New frontiers of clinical genomics, including integration with electronic health records (EHRs) and wearables 

28:24 The physiology and genetics of athletic performance and the inspiration behind the ELITE study

33:54 Psychological drivers and effects of human performance

37:57 Euan’s interest in generative AI for developing novel therapies

41:32 Closing remarks 

Find out more

• The Ashley Lab (https://ashleylab.stanford.edu/)

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