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Abstract

Dr. Platt’s research centers on proteolytic mechanisms of tissue remodeling during disease progression using both experimental and computational approaches. Many of his diseases of focus are health disparities in the U.S., but global health concerns: pediatric strokes in sickle cell disease, HIV-mediated cardiovascular disease, predictive medicine for breast cancer, and also COVID-19. His research has taken him to South Africa and Ethiopia for collaborative work to find solutions for low resource settings, which have broadened opportunity and forced creative solutions. Centered agents are the cysteine cathepsins, which are the most potent mammalian collagenases and elastases, but cathepsin pharmacological inhibitors continue to fail human clinical trials, mostly due to unexpected side effects. This suggests there are underlying regulatory behaviors or feedback loops yet to be elucidated. During this seminar, Dr. Platt will discuss 1) experimental and computational tools to better quantify and model protease activity, 2) concept of a proteolytic network in tissue destructive diseases, and 3) fundamental insights and consequences of the underlying enzymology to improve pharmacological targeting and application for multiple diseases.