Michael Wolfe

Michael Wolfe is a Professor at the University of Kansas School of Pharmacy, leading research on intramembrane-cleaving proteases (I-CLiPs), with a focus on γ-secretase's role in Alzheimer's disease. His lab investigates γ-secretase's mechanism, substrate recognition, and therapeutic targeting, particularly how familial Alzheimer's mutations affect enzyme function. Key contributions include developing transition-state analog inhibitors, identifying presenilin as γ-secretase's catalytic component, and elucidating the enzyme's dual proteolytic activities. Research extends to other I-CLiPs like Rhomboid and signal peptide peptidase, exploring their roles in human parasites and disease.

Research Interests:

• Mechanisms of intramembrane proteolysis
• γ-Secretase structure/function relationships
• Alzheimer's disease pathogenesis
• Design of protease inhibitors
• Therapeutic strategies targeting membrane-embedded enzymes

Recent Articles Overview: Recent work highlights γ-secretase's substrate interactions, effects of familial mutations on enzyme activity, and novel inhibitors. Studies also address non-Amyloid Alzheimer's pathways and γ-secretase's role in Notch signaling and malaria parasites. These findings advance understanding of neurodegenerative mechanisms and drug development.