Michael S. Wolfe

Michael S. Wolfe serves as the Mathias P. Mertes Professor of Medicinal Chemistry within the Department of Medicinal Chemistry at the University of Kansas School of Pharmacy. His research program focuses on intramembrane-cleaving proteases (I-CLiPs) and their critical roles in human disease pathogenesis, particularly Alzheimer's disease and malaria.

His educational background includes:

• Ph.D. in Medicinal Chemistry, University of Kansas
• M.S. in Medicinal Chemistry, University of Kansas
• M.A., Harvard University
• B.S. in Chemistry, Philadelphia College of Pharmacy and Science

Dr. Wolfe's research centers on the chemistry and biology of γ-secretase, an aspartyl protease responsible for generating amyloid β-peptide in Alzheimer's disease and mediating Notch signaling in cell differentiation. His lab pioneered transition-state analogue inhibitors to characterize γ-secretase and identified presenilin as its catalytic component. Key discoveries include the enzyme's dual proteolytic functions (endopeptidase and carboxypeptidase activities), the impact of Alzheimer's-causing presenilin mutations on Aβ trimming, and the identification of substrate docking sites. Current work extends to other I-CLiPs like signal peptide peptidase and Rhomboid, with emphasis on developing chemical probes for therapeutic applications in malaria caused by Plasmodium falciparum.

Analysis of his 2014-2016 publications reveals consistent focus on γ-secretase mechanism, inhibitor development, and structural biology. His work spans biochemical characterization, substrate processing studies, and therapeutic strategies targeting Alzheimer's disease, with increasing exploration of parasite proteases for malaria treatment. The publications demonstrate interdisciplinary integration of medicinal chemistry, neuroscience, and molecular biology to address fundamental questions in protease biology.

Dr. Wolfe leads an active research laboratory investigating membrane-embedded proteases, with emphasis on elucidating catalytic mechanisms, substrate recognition, and developing therapeutic prototypes. His work bridges basic science and translational applications through chemical probe development and inhibitor design.