Wu Tsai Neuro Seminar w/ X. William Yang – SRP Livestream Locations

Good morning SOM Stanford Research Park Community,

We invite you to join us for today’s Neurosciences Seminar. The seminar will be held in-person on the main Stanford campus with 3 satellite viewing locations in Stanford Research Park.

🗓️ May 14, 2026

Beyond the inherited CAG: Decoding a neuronal-selective pathogenic cascade in Huntington’s disease
X. William Yang, MD, PhD

University of California, Los Angeles | Host: Andy Tsai (Wyss-Coray Lab)

Huntington’s disease (HD) is caused by a CAG repeat expansion in the huntingtin gene, and disease onset as well as clinical progression are modified by multiple GWAS loci enriched for DNA repair genes, including multiple mismatch repair (MMR) genes and FAN1. Here, I will present a series of studies—primarily using mouse genetic models of HD—to illustrate key pathogenic steps that lead to selective pathogenesis of the striatal medium spiny neurons (MSNs), the most vulnerable neuronal cell types in HD. Our studies show that a subset of HD GWAS/MMR genes (i.e.., Msh3 and Pms1) are key drivers of somatic CAG repeat expansion in the endogenous murine mutant huntingtin (mHtt), with MSNs showing the fastest rates of expansion. Consequently, these mice display somatic repeat length– and threshold-dependent, molecular and pathological phenotypes. Downstream of somatic repeat expansion, polyglutamine (polyQ)-expanded mHtt species accumulate in the nuclei of affected neurons, where they elicit proteotoxicity leading to profound chromatin defects. The latter include erosion of epigenomic signatures of MSN identity. Together, our studies reveal distinct pathogenic steps in HD pathogenesis and provide new insights and model platforms to develop therapies.

⏰ Time: 12:00-1:00 PM (PT)
Come 15 minutes early (11:45 AM) to enjoy coffee, cookies, and conversation with the speaker and your colleagues (main campus location only)

📍 Locations:

• Main Campus (in person): Gunn Rotunda (E241), Stanford Neurosciences Building
• Stanford Research Park satellite locations:
  • 3172 Porter Drive, Room 253
  • 3174 Porter Drive, Room 140
  • 1070 Arastradero Road, Room 211

Learn about the SRP satellites »

Learn more and get involved:

• Nominate speakers for the 2026-2027 seminar series
• About the Wu Tsai Neurosciences Seminar Series »
• Sign up to dine or meet with the seminar speakers »
• See all upcoming and past seminars »
• Sign up for Wu Tsai Neuro’s mailing list »
• Join the #neuroscience slack channel »

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Best regards,
Emily Elrod (she/they)