时间：2024年10月24日（周四）16:00-17:30 

Time：4:00-5:30 PM, Thursday, Oct 24, 2024

地点：西湖大学云谷校区E10-201教室

Venue: E10-201, Yungu Campus

主持人：西湖大学理学院 张鑫教授

Host: Professor Xin Zhang, School Science, Westlake University

主讲人/Speaker：

Professor Jeffery W. Kelly

Lita Annenberg Hazen Professor of Chemistry, Scripps Research

Jeffery W. Kelly was born in Medina, New York, in 1960. He earned his B.S. in chemistry from SUNY Fredonia (1982), followed by a Ph.D. in organic chemistry from the University of North Carolina (1986) and post-doctoral training at The Rockefeller University (1986-89). He is currently the Lita Annenberg Hazen Professor of Chemistry at The Scripps Research Institute, where he has served as Dean of the Graduate Program, Vice President of Academic Affairs, and Chairman of Molecular Medicine and Chemistry.

The central theme of Kelly's research is to explore the chemistry and biology of protein folding, misfolding, and aggregation, which are linked to various human diseases. Insights from his work inform new therapeutic strategies for diseases related to protein conformation.

Notably, Kelly's lab discovered tafamidis (Vyndaqel/Vyndamax), the first drug to slow the progression of amyloid disease by inhibiting protein aggregation. This breakthrough involved translating a genetic observation into a mechanistic understanding of amyloid disease prevention through interallelic trans suppression. Tafamidis stabilizes the native tetrameric conformation of transthyretin, significantly slowing its aggregation.

An author of over 400 papers (h-index = 107), Kelly is an elected member of the National Academy of Sciences and the American Academy of Arts and Sciences. His accolades include the Wolf Prize in Chemistry, the Breakthrough Prize in Life Sciences, and several other prestigious awards. He has also mentored over 115 trainees in academia and industry.

报告题目/Title:

Scientific Origins of Drugs that Slow Neurodegeneration

讲座摘要/Abstract:

Strong published human genetic evidence supports the hypothesis that protein aggregation causes neurodegeneration or amyloid diseases. There are now 9 regulatory agency–approved drugs that slow neurodegeneration by modulating protein aggregation, providing compelling pharmacological evidence that protein aggregation drives the degeneration of nervous systems and other organ systems. Our laboratory had the privilege of discovering the first regulatory agency–approved drug that slows the progression of transthyretin amyloidosis, the third most prominent amyloid disease behind Alzheimer’s and Parkinson’s diseases. The first half of the seminar will focus on the evidence demonstrating the identical mechanisms of (1) the transthyretin tetramer-stabilizing, anti-aggregation drugs that we conceived and developed by structure-based design and (2) the interallelic trans-suppressor mutations we characterized in compound heterozygotic patients that protect against transthyretin amyloid disease: both slow tetramer dissociation and subsequent aggregation. The transthyretin native state kinetic stabilizer tafamidis, sold by Pfizer and discovered by our laboratory, is currently being used in >55,000 transthyretin amyloidosis patients to extend their lifespan and healthspan by slowing amyloid disease progression. The next section of the seminar will focus on how we discovered light chain kinetic stabilizer drug candidates through high-throughput screening and subsequent structure-based design medicinal chemistry efforts. Clinical trials on one of these light chain stabilizers will commence in early 2025. The seminar will end by describing the mechanisms of action of the other FDA-approved drugs that modulate protein aggregation and what we have learned from these drugs collectively about the etiology of human amyloid diseases.

讲座联系人/Contact:

科技合作部 Sci-tech02@westlake.edu.cn