2025 Duane D. Miller Lectureship: Featuring Michael S. Wolfe, PhD | Tues. May 20, 9 am | College of Pharmacy Building Room 102

Join the College of Pharmacy for the 2025 Duane D. Miller Lectureship Featuring Michael S. Wolfe, PhD

Mathias P. Mertes Professor of Medicinal Chemistry, University of Kansas, our 2025 Lectureship winner.

The event will take place on May 20 from 9:00 am - Noon at the UT Health Science Center College of Pharmacy Building, Room 102.

Lecture Title: Integrating Chemistry and Biology to Solve Alzheimer's Disease

Dr. Wolfe's lecture will cover his research into Alzheimer's Disease, a progressive neurodegenerative disorder primarily associated with old age that presents as loss of memory and cognition. Plaque deposition of the 42-residue form of the amyloid β-peptide (Aβ42) in the brain is an early pathological event, occurring many years before the appearance of symptoms. Genetics and biochemistry support the amyloid hypothesis ofAlzheimer pathogenesis: Dominantly inherited mutations that cause Alzheimer's disease in midlife are found in the substrate and enzyme that produce Aβ, and these mutations generally skew Aβ production toward the aggregation-prone Aβ42. Nevertheless, doubts remain whether Aβ42 is the primary disease driver and most appropriate therapeutic target. Here I will present our work on the protease γ-secretase that produces Aβ, including the development of chemical probes that contributed to the characterization, purification, identification, and mechanistic understanding of this membrane-embedded protease complex and its role in pathogenesis. Our recent studies have led to an unexpected and counterintuitive amyloid-independent hypothesis: Alzheimer-causing mutations lead to stalled, stabilized γ-secretase enzyme-substrate complexes that cause age-dependent synaptic degeneration. That is, the stalled process-not the products- of Aβ generation may be the key disease driver of Alzheimer's disease. Implications of this new hypothesis for Alzheimer drug discovery will be discussed.

For more information, please visit: https://bit.ly/4cYeV7S