The Genetics Podcast

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. We’re re-running this episode for its enduring lessons on patient advocacy, rare disease parenting, communication, and citizen science. 

Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Sharon and a discussion of the personal experience with rare disease that started her journey
03:47 Reasons Sharon decided to establish the first layperson-led biobank
05:34 Challenges with setting up the biobank infrastructure
07:00 Balancing financial factors in a non-profit organization 
09:30 Recent patterns and future insight into rare disease drug discovery framework and regulation
15:32 Barriers to widespread collaboration and cooperation in rare disease research, and why it should be approached from a public health perspective
18:12 Background and experiences from the iHope Genetic Health program in low- to middle-income countries
24:44 Sharon’s perspective on challenges with the Genetic Information Non-discrimination Act
28:49 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 communities
34:34 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 work
40:18 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Dr. Carl Anderson, Senior Group Leader and Head of the Human Genetics Programme at the Wellcome Sanger Institute, where he leads the Genomics of Inflammation and Immunity Group. They discuss IBDVerse, the single-cell atlas Carl's team built to map genetic effects on gene regulation across gut cell types, how coding and non-coding variants converge on shared biological pathways in inflammatory bowel disease, and Carl's vision for longitudinal multi-omics cohorts built around the sickest and most underrepresented hospital patients.
Show Notes
0:00 Intro to The Genetics Podcast
00:58 Welcome to Carl
02:05 The origins of IBDVerse and mapping genetic effects on gene regulation across gut cell types in IBD
05:43 How anti-TNFs and newer genetically-supported IBD drugs have reshaped treatment 
08:04 Genetic versus environmental contributions to IBD
09:53 Using single-cell data to uncover IBD disease subtypes
13:22 Drug sequencing and immunogenicity in treatment response
16:52 The backstory of building the IBDVerse atlas at scale
20:29 How coding and non-coding IBD variants converge on the same genes and pathways
23:38 The case for pathway-specific polygenic risk scores
28:17 Building a longitudinal multi-omics dataset to predict IBD progression and drug response
30:08 Why Sanger's next cohort targets sick and underrepresented patients rather than healthy volunteers
34:07 What Carl looks for when interviewing PhD students and faculty candidates 
39:20 A call to junior scientists and closing remarks
Find out more:
IBDverse study

This week on The Genetics Podcast, Patrick is joined by Dr. Pradeep Natarajan, Director of Preventive Cardiology at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. They discuss the discovery of clonal hematopoiesis as a driver of cardiovascular disease, the inflammatory mechanisms and emerging therapies targeting it, the growing clinical case for polygenic risk scores, and Pradeep's upcoming move to lead cardiometabolic and human genetics research at Amgen.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Pradeep
01:30 The origin story of clonal hematopoiesis (CH) as a cardiovascular risk factor 
09:41 CH mutations such as TET2 that are linked to cardiovascular disease
12:27 Evidence tying inflammation to CH and drugs that could target it
16:49 TenSixteen Bio’s strategy for targeting CH and the challenge of finding the right patients
21:33 Trajectory of CH across age and somatic mosaicism beyond blood
26:44 How polygenic risk scores fill a gap in cardiovascular risk prediction
34:49 The future clinical applications of polygenic risk scores
39:20 The challenge of standardizing polygenic risk scores for clinical and regulatory use
42:27 Pradeep's move to pharmaceutical company Amgen and his reasons for it
46:23 Closing remarks
Find out more:
Clonal hematopoiesis paper

This week on The Genetics Podcast, Patrick is joined by Dr. Christopher Walsh, Professor of Pediatrics and Neurology at Harvard Medical School, Chief of Genetics and Genomics at Boston Children's Hospital, and HHMI Investigator. They discuss his path from neurobiology to human genetics, how somatic mosaicism in the brain drives disease from epilepsy to Alzheimer's, and what this reveals about new therapeutic targets for neurodegeneration.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Chris
01:18 Chris’ path from neurobiology to human genetics
04:55 How collaboration and mentorship have shaped Chris' career
06:59 Somatic mosaicism and genetic mutations in the brain, from epilepsy to Alzheimer’s
13:56 Repurposing cancer therapeutics and targeting DNA damage as new approaches to Alzheimer's
15:29 A shared pattern of DNA damage across neurodegenerative diseases and the mechanism behind it
19:36 How healthy neurons accumulate mutations with age and what that means for the brain
23:21 How mutation rates and patterns vary across cell types
26:23 How genome quality control and synaptic pruning may explain both brain development and neurodegeneration
30:33 Why some people maintain a healthy brain into old age
33:57 Chris’ advice for early-career scientists on pursuing goals
36:43 Closing remarks
Find out more:
https://walshlab.org/

This week on The Genetics Podcast, Patrick is joined by Yentli Soto Albrecht, physician-scientist in training and founder of CureC9. They discuss how losing her father to C9orf72 ALS, and later learning her own genetic risk, reshaped the direction of her career. The conversation explores the biology linking the C9 repeat expansion to ALS and FTD, and how CureC9 is removing barriers across biomarkers, therapeutics, and patient samples to accelerate progress toward a cure.
Show Notes
0:00 Intro to The Genetics Podcast
00:58 Welcome to Yentli
02:34 How Yentli's father's C9 ALS diagnosis and her own genetic risk led her to pivot her research career toward curing it
06:41 The biology of the C9orf72 repeat expansion and how TDP-43 dysregulation links it to ALS and FTD
11:40 Therapeutic strategies targeting TDP-43 pathology in ALS and FTD
15:35 The state of biomarkers for ALS and FTD, and why C9-FTD trials lag behind ALS
22:08 How Yentli is lowering barriers for biomarker, cell line, and drug development through CureC9
30:40 Call for collaborators and where to follow Yentli 
32:59 Closing remarks
Find out more: CureC9