Manu O. Platt

Manu O. Platt

Georgia Tech

and

Emory University

Quantitative Dissection of Proteolytic Networks Governing Tissue Remodeling

In many tissue engineering strategies and tissue-destructive disease progression, mechanisms of proteolytic remodeling of extracellular matrix and tissue structure are implicated. This talk will discuss complex variability and non-intuitive cell behaviors and enzyme kinetics when targeting cysteine cathepsins, the most potent mammalian collagenases and elastases, that has led to failure of cathepsin pharmacological inhibitors to pass human clinical trials in the United States. Cysteine cathepsins are proteases capable of cathepsin cannibalism, where one cathepsin hydrolyzes another with substrate present, and cathepsin inhibitors continue to fail clinical trials due to side effects, not efficacy, motivating greater understanding of multiple proteases working in a proteolytic network.