Michael Li
Education:
B.A. Washington University in St. Louis (2014)
Current Position:
8th Year MSTP
4th Year Medical Student
Advisor:
Dr. Jessica Seeliger
Graduate Program:
Molecular and Cellular Pharmacology
Research Interest:
The rise of drug-resistant forms of Mycobacterium tuberculosis (Mtb) drives the need to develop new inhibitors and characterize pharmacologically vulnerable targets. A promising family of enzyme targets is the serine hydrolases. Serine hydrolases have diverse enzymatic activities, but largely uncharacterized functions, although those that have been studied include enzymes essential to Mtb survival. After a screen of inhibitors that covalently modify the catalytic serine shared by members of the serine hydrolase superfamily, we have identified a series of 4 structurally similar compounds with a range of activity against Mtb. Two of these compounds have low micromolar inhibitory concentrations. A chemoproteomic labeling strategy identified the serine hydrolases selectively inhibited by these two hit compounds. These results support the serine hydrolase family as is a promising set of targets within Mtb. We are now exploring the mechanism of action for these inhibitors.
Publications:
(MSTP-supported publications indicated with an*)
Li M., Patel H.V., Cognetta A.B., Smith T.C., Mallick I., Cavalier J.F., Canaan S., Aldridge B.B., Cravatt B.F., Seeliger J.C. (2021) A Competitive Activity-Based Protein Profiling Platform Yields Cell Wall Synthesis Inhibitors Active Against Replicating and Non-Replicating Mycobacterium Tuberculosis. BioRxiv; doi: https://doi.org/10.1101/2021
P.C. Hsu, H. Wu, T. J. Carney, M. T. McDowell, Y. Yang, E. C. Garnett, M. Li, L. Hu, and Yi Cui, "Passivation Coating on Electrospun Copper Nanofibers for Stable Transparent Electrodes," ACS Nano 6(6) 5150-5156 (2012)
***Patel H.V., Li M., Seeliger J.C. (2018) Opportunities and Challenges in Activity-Based Protein Profiling of Mycobacteria. In: Cravatt B., Hsu KL., Weerapana E. (eds) Activity-Based Protein Profiling. Current Topics in Microbiology and Immunology, vol 420. Springer, Cham
