Disease Mechanisms

Identifying proteins with reactive modifications operant in disease states and higher-ordered processes.


Another goal of our research is to use RP-ABPP first to discover and identify probe-reactive modifications in proteins that play roles in disease states and then to understand the cellular determinants of their installation that impact function. This effort will involve adapting the technology for in vivo studies and inhibitor screening. RP-ABPP can be used to monitor changes in cofactor fractional occupancy that might afford an unrecognized level of metabolic regulation in cells. In addition, Our unpublished preliminary data supports future in vivo and inhibitor screening applications. If the proposed applications are effective, the method could afford impactful discoveries through collaborative efforts that couple system-wide chemoproteomic profiling with sophisticated disease models.

Selected Publications

Lin Z, Wang X, Bustin KA, He L, Suciu RM, Schek N, Ahmadi M, Hu K, Olsen EJ, Parsons WH, Witze ES, Morton PD, Gregus AM, Buczynski MW, Matthews ML. Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes bioRxiv (2020) [PDF]