EP 247: Why neurons accumulate mutations like clockwork: Somatic mosaicism and neurodegeneration with Christopher Walsh of Boston Children's Hospital

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/