Functional Target Discovery by Quantitative Chemical Proteomics

Seminar | August 14 | 11 a.m.-12 p.m. | 9 Lewis Hall

 Professor Chu Wang, College of Chemistry and Molecular Engineering, Peking University, China

 College of Chemistry

Genome sequencing projects have revolutionized our view of the complexity of prokaryotic and eukaryotic proteomes, however, we are also left with a daunting challenge of functionally annotating these large number of predicted proteins. Chemical proteomic methods, such as activity-based protein profiling (ABPP), have been developed aiming at systematically discovering new functional targets directly from native proteomes. In this talk, I will present a couple of projects from my laboratory which combine ABPP-based chemical proteomic, biochemical and computational strategies to uncover functional targets of specific post-translational modifications or bioactive ligands in proteomes. In the first project, we developed a highly efficient chemical probe for profiling target proteins and residue sites of protein carbonylations in proteomes and its application in uncovering endogenous carbonylated targets during the course of ferroptosis, a recently defined non-apoptotic cell death that is heavily dependent on intracellular iron and elevated lipid peroxidation. In the second project, we showed that a flavonoid compound isolated from the Chinese traditional herbal medicine is an effective agent to improve hepatic steatosis. By employing a quantitative ABPP strategy, we discovered the flavonoid binds to key enzymes in the fatty acid metabolic pathway, accelerate the metabolic rate of fatty acids in the liver and ameliorates the symptoms associated with hepatic steatosis.

Dr. Chu Wang obtained his B.S. degree in Biology from University of Science and Technology of China (USTC) in 2001 and his Ph.D. degree with Professor David Baker in 2007 from University of Washington. He did his postdoctoral training with Professor Benjamin F. Cravatt at The Scripps Research Institute from 2009 to 2013 and was supported by NIH / NIEHS Pathways to Independence (K99/R00) postdoctoral award. He started as an assistant professor at Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University in December, 2013 and is also affiliated with Synthetic and Functional Biomolecules Center (SFBC) and Peking-Tsinghua Center for Life Sciences (CLS) as a Principal Investigator. His current research programs focus on the development and application of multi-disciplinary tools in chemoproteomics, biochemistry, bioinformatics and computational structure biology to streamline efforts in the functional annotation of uncharacterized enzymes and drug design in the post-genomic era.