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Chemical biology, small-molecule synthesis, intramembrane hydrolases

Enzyme-mediated hydrolysis is a ubiquitous component of numerous metabolic pathways in the body. Nature has developed a number of chemistries within hydrolase active sites to cleave a diverse array of biological substrates. The Parsons lab studies enzymes that use serine and threonine residues to catalyze turnover of their substrates. A subset of these enzymes with intramembrane active sites are of particular interest due to their unique biochemistry as well as their involvement in pathways underlying metabolic and neurological diseases, including Parkinson’s disease and type 2 diabetes. 

The Parsons lab exploits the active site chemistry of these hydrolases to create new chemical probes for this enzyme class. Drawing upon methodology from synthetic chemistry, biochemistry, molecular biology, and medicinal chemistry, research in the Parsons lab focuses on the development of small molecule tools to study the physiological roles of intramembrane hydrolases.

Parsons teaches general and organic chemistry courses in the department. During the fall semester of 2025, he is teaching lecture and lab sections of CHEM 205: Principles of Organic Chemistry. During the spring semester of 2026, he is teaching lecture and lab sections of CHEM 254: Bioorganic Chemistry.

(Note: An asterisk indicates an 91ֱ�� student/graduate coauthor)

• Chvatal J*; Nguyen DT*, Xie AS*, Parsons WH. "Synthesis and Evaluation of N-Arylsulfonylated Succinimides as Activity-Based Probes." Synlett 2025, 36. .
• Davies CC*, Hu R-M, Kamitsuka PJ*, Morais GN*, Gonzalez RS*, Bustin KA, Matthews ML, Parsons WH. "Activity-based protein profiling of RHBDL4 reveals proteolysis of the enzyme and a distinct inhibitor profile." ACS Chem Biol 2024, 19, 1674–1682. .
• Parsons WH, Cravatt BF. "Activity-based protein profiling." In Advanced Chemical Biology: Chemical Dissection and Reprogramming of Biological Systems; Hang HC, Pratt MR, Prescher JA, Eds; Wiley-VCH, 2023; pp 503–526.
• Wang X, Lin Z, Bustin KA, McKnight NR, Parsons WH, Matthews ML. “Discovery of potent and selective inhibitors against protein-derived electrophilic cofactors.” J Am Chem Soc. 2022, 144, 5377–5388. .
• Parsons WH, Rutland NT*, Crainic JA*, Cardozo JM*, Chow AS*, Andrews CL*, Sheehan BK*. Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL. Bioorg Med Chem Lett. 2021, 49, 128290. .