On Tuesday, May 20, 2025, we were honored to host Michael S. Wolfe, PhD, Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, the winner of the 2025 Duane D. Miller Lectureship.
About Michael S. Wolfe
Michael S. Wolfe received his B.S. in chemistry in 1984 from the Philadelphia College of Pharmacy and Science and Ph.D. in medicinal chemistry in 1990 from the University of Kansas. After postdoctoral stints at the University of Kansas (medicinal chemistry) and the U.S. National Institutes of Health (cell biology), he joined the faculty of the University of Tennessee in Memphis in 1994. In 1999, he moved to Harvard Medical School and Brigham and Women’s Hospital, where his work focused on understanding the molecular basis of Alzheimer’s and related disorders and identifying effective approaches for pharmacological intervention, becoming Professor of Neurology in 2008. He joined the University of Kansas faculty in 2016 as the Mathias P. Mertes Professor of Medicinal Chemistry. Awards for his work include the Sato Memorial International Award in bioorganic and medicinal chemistry from the Pharmaceutical Society of Japan (2003), the MetLife Award for Biomedical Research (2008), a Zenith Fellows Award from the Alzheimer’s Association (2008), and the Potamkin Prize from the American Academy of Neurology (2009).
Dr. Wolfe led a lecture titled ‘Integrating Chemistry And Biology To Solve Alzheimer’s Disease” covered 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 appearance of symptoms. Genetics and biochemistry support the amyloid hypothesis of Alzheimer 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.
Ahmed Rakib Presented with the 2025 Duane D. Miller Award in Drug Discovery
Congrats also goes to our 2025 Duane D. Miller Award in Drug Discovery, graduate student Ahmed Rakib, who was recognized for his exceptional research at UT Health Science Center College of Pharmacy.
Thank you to our Duane D. Miller Endowment Donors and to everyone who attended this event!
About the Duane. D. Miller Lectureship
The UTHSC College of Pharmacy Drug Discovery Center (UTCoP DDC) established the “The Duane D. Miller Lectureship” and its related graduate student award, “The Duane D. Miller Award in Drug Discovery” in 2023. This lectureship and student award honor Dr. Duane Miller, Professor Emeritus at UTCoP, for his exceptional and long-lasting impacts on the establishment of the Medicinal Chemistry programs in UTCoP in 1992 after more than 20 years successful career at the Ohio State University, and his accomplishments in inventing several small molecule investigational new drugs (e.g., Enobosarm, Sabizabulin) that have moved to advanced clinical trials.
The Duane D. Miller Award in Drug Discovery recognizes a graduate student for outstanding achievement in small molecule drug discovery and development research. The first named award for students in the UTCoP graduate program carries a monetary award, generously provided by Dr. Miller himself for the inaugural year 2023
The annual Duane D. Miller Lectureship Award recognizes a small molecule drug discovery expert, with Dr. Miller being the inaugural awardee.
For more information, visit: https://bit.ly/4cYeV7S