Event

Abstract
Hydrolases represent one of the largest classes of enzymes in the body and play essential roles in physiological processes ranging from inflammation to nervous system signaling. Despite the prevalence and importance of this enzyme class, the biological functions of many hydrolases have yet to be determined. Among these less characterized members are rhomboid intramembrane proteases (RIPs), which have nevertheless generated significant interest due to their membrane-embedded active sites and association with several health disorders. Mutation and dysregulation of these enzymes in neurodegenerative diseases and multiple types of cancer motivates the development of an enhanced understanding of their physiological functions as well as an investigation of their potential to serve as therapeutic targets. Suitable methods to conduct these studies, however, are currently lacking. My team of undergraduate researchers is currently employing activity-based protein profiling (ABPP) technology to develop chemical probes to study the human RIPs. In this talk, I will describe our development of ABPP assays for the human RIPs, RHBDL4 and PARL, and the use of these assays for characterization of their active proteoforms and inhibitor discovery. I will also discuss our ongoing efforts to establish ABPP assays for the remaining three human RIPs (RHBDL1, RHBDL2, and RHBDL3). We envision that the chemical tools developed through this work will facilitate characterization of these enzymes and provide valuable lead compounds for selectively modulating their functions.

Biography

William (Will) Parsons grew up primarily in Chattanooga, Tennessee and completed his undergraduate degree in Chemistry and Mathematics at Williams College, where he conducted research with Prof. Sarah Goh developing block copolymers as potential drug delivery vehicles. He obtained his PhD in Chemistry from Stanford University working with Prof. Justin Du Bois on the development of saxitoxin-derived molecular probes for the study of voltage-gated sodium channels. He then conducted postdoctoral studies in the lab of Prof. Benjamin Cravatt at The Scripps Research Institute and used activity-based protein profiling technology to characterize hydrolases lacking functional annotation. He began his independent career at Oberlin College in 2017, where he is now an Associate Professor of Chemistry and Biochemistry. In addition to teaching general and organic chemistry courses, he works with his team of undergraduate researchers to develop chemical probes for understudied enzymes with a particular focus on the rhomboid intramembrane proteases.

Inquiries: nguyeny@sas.upenn.edu

Location: Carolyn Hoff Lynch Lecture Hall