The Genetics Podcast

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

Euan Ashley, Chair of the Department of Medicine at Stanford and co-founder of biotech firms, shares insights from his groundbreaking work in ultra-rapid genome sequencing. He highlights a pivotal case of diagnosing a newborn's cardiac condition in just eight hours. Euan discusses the integration of AI and wearables in preventive medicine, as well as the genetics behind elite athletic performance. Additionally, he explores the ethical considerations of widespread genetic testing and the potential of generative AI in developing novel therapies.

This week on The Genetics Podcast, Patrick is joined by Kent Rogers, Chief Executive Officer at EveryONE Medicines. They discuss Kent’s journey across every side of the desk in the drug discovery space, EveryONE Medicines’ efforts to develop antisense oligonucleotides for ultra-rare diseases, and the need to adapt regulatory models for n-of-1 therapies.Show Notes: 00:00 Intro to The Genetics Podcast00:59 Welcome to Kent and his experiences across every side of the pharma ‘desk’06:00 Challenges of commercialization for ultra-rare disease therapies and the advantage of antisense oligonucleotides (ASOs) 10:28 EveryONE Medicines’ approach to regulatory bodies12:30 Regulatory feedback and expectations from EveryONE Medicines’ platform-based approach to n-of-1 therapies15:47 Differences in regulatory requirements for rare disease across countries 19:53 Insights from being on different sides of the drug development industry22:40 Differences in healthcare systems across countries that can facilitate or impede drug development26:57 Rationale behind focusing on ASOs for treating rare diseases 28:03 Building EveryONE Medicines and Kent’s approach to leadership33:20 Lessons from Kent’s career37:17 Closing remarks Find out moreEveryONE Medicines (https://www.eomeds.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 Matt Burgess, genetic counselor, host of the Demystifying Genetics podcast, and Adjunct Professor at Bay Path University. They discuss the evolution of genetic counseling, ethical challenges in gene therapy, and Matt’s experiences with his podcast.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Matt02:09 Matt’s run-ins with Olivia Newton John while working at Austin Hospital in Melbourne04:34 Matt’s background and path to genetic counseling 06:58 The evolution of the field of genetic counseling over time and the role of counselors12:47 Matt’s work on rare disease AP-4 hereditary spastic paraplegia (AP-4-HSP) and the ethical considerations of gene therapy20:22 Balancing the needs and expectations of individuals and families in counseling 23:06 Rebranding negative connotations of the word “counseling”  26:58 Memorable episodes from Matt’s podcast Demystifying Genetics34:31 Differences in genetic counseling and healthcare in the US versus Australia and the UK40:00 Matt’s current work on writing a novel, starting a company called Rosalind Genetics, and being involved in genetic education42:47 The potential and drawbacks of AI models in the context of genetic counseling and information46:46 Closing remarksFind out moreDemystifying Genetics (https://demystifying-genetics.buzzsprout.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 Salvador Rico, Chief Medical Officer at Encoded Therapeutics. They discuss Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and fundamental challenges and exciting advances in the genetics field.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Salvador and how he became involved in drug development11:01 Frustrations and rewards of the genetics field13:59 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)19:46 Risk of liver issues in gene therapy trials and attempts to mitigate them24:22 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team27:22 Steps towards therapeutic targeting of gene regulatory elements 30:04 Advantages of different methods for drug delivery 32:31 DNA- versus RNA-based therapy 34:56 Insights from approaches in other fields, including psychiatry36:35 Considerations for using natural history studies40:32 Expectations and goals for Encoded Therapeutics’ current and upcoming studies43:17 Closing remarksFind out moreEncoded Therapeutics (https://encoded.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 Leeland Ekstrom, CEO and co-founder of Nashville Bio. They discuss how Leeland went from being a consultant on a project for Vanderbilt University to a co-founder of a start-up and the unique aspects of NashBio’s clinical and genetic database.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Leeland and the origin story of Nashville Bio05:13 Process of setting up NashBio’s genome resource with 250K individuals11:52 How different pharmaceutical companies responded to NashBio’s database and its unique advantages compared to others17:50 Key priorities for applications of the resource beyond target discovery20:19 The process of selecting additional gaps that NashBio’s services can fill versus letting others fill them25:02 Advantages at Vanderbilt Medical Center that facilitated the project and how it can be replicated at other centers30:32 Immediate and long-term impacts of current NIH funding cuts on biotech and academia36:43 NashBio’s current major focuses and future goals39:20 Closing remarksFind out moreNashBio (https://nashbio.com/)Press release: Alliance for Genomic Discovery completes 250,000 whole genomes to accelerate drug discovery (https://www.illumina.com/company/news-center/press-releases/press-release-details.html?newsid=b4b0c901-f8a2-4802-a4ef-b81167e24cfe) 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 Sharon Terry, President & CEO of Genetic Alliance. They discuss how Sharon established a layperson-led biobank, her long-term work on rare diseases and patient advocacy, and her program to bring genetic technology to patients in low- to middle-income countries.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Sharon and a discussion of the personal experience with rare disease that started her journey03:47 Reasons why Sharon decided to establish the first layperson-led biobank05:34 Challenges with setting up the biobank infrastructure07:00 Balancing financial factors in a non-profit organization 09:30 Recent patterns and future insight into rare disease drug discovery framework and regulation15:32 Barriers to widespread collaboration and cooperation in rare disease research, and why it should be approached from a public health perspective18:12 Background and experiences from the iHope Genetic Health program in low- to middle-income countries24:44 Sharon’s perspective on current challenges with the Genetic Information Non-discrimination Act28:49 Sharon’s lessons learned in her patient advocacy and policy work, and her hopes for future legislation 33:04 Sharon’s hopes for improved access to genetic testing and treatment for children in underserved communities34:34 How Sharon learned about rare diseases and genetics as a “homeschooling mom without a degree”37:54 Insights into how elements of spirituality can support advocacy work40:18 Closing remarksFind out moreGenetic Alliance (https://geneticalliance.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