Michael S. Wolfe, PhD, of the University of Kansas for Pharmacology’s Seminar Series

Michael S. Wolfe, PhD
Mathias P. Mertes Professor
Department of Medicinal Chemistry
University of Kansas

Seminar title: “In Search of the Pathogenic Trigger of Alzheimer’s Disease”

Dr. Wolfe is a world-leading expert in intramembrane proteolysis and drug design targeting the γ-secretase against Alzheimer’s disease. His lab reported the first designed inhibitors of γ-secretase and used these as tools to characterize, isolate, identify and purify this unusual multi-component membrane protein complex. Most notably, they discovered that presenilin, mutated in early-onset familial Alzheimer’s disease (FAD), is a novel intramembrane aspartyl protease. They have elucidated fundamental biochemical, mechanistic and structural features of this protease complex and developed different classes of inhibitors as biological tools and therapeutic prototypes. In the past few years, they have advanced the biochemical understanding of the multiple proteolytic functions of γ-secretase, how it recognizes substrates, and how substrate recognition and processing is altered by Alzheimer-causing mutations. Most recently, they have analyzed effects of FAD mutations on all proteolytic processing events on amyloid precursor protein (APP) substrate by γ-secretase, identified new γ-secretase modulators with unique properties, and developed dynamic models of substrate processive proteolysis by γ-secretase and effects of Alzheimer-causing mutations through collaborative experiments and simulations.

Host: Yinglong Miao, PhD

1131 Bioinformatics (Zoom by request)
130 Mason Farm Rd
Chapel Hill, North Carolina 27516
United States
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For those unable to attend, a zoom link is available upon request to Mimi Le