51st UC San Diego Annual Lectureship in Biochemistry, April 24 - 25, 2025

(formerly Calbiochem/EMD Millipore/MilliporeSigma) 

Sponsored by WP CAREY Foundation

Activity-Based Proteomics

Speaker Dr. Benjamin F. Cravatt, Professor and Norton B. Gilula Chair of Chemical Biology, Department of Chemistry, Scripps Research
2022 Wolf Prize in Chemistry

Thursday, April 24th, 2025 at 4:00 pm:

"Enzyme and Inhibitor Discovery on a Global Scale"
Health Sciences Education Center Auditorium, Lower Level, Skaggs School of Pharmacy & Pharmaceutical Sciences Bldg.
UC San Diego

Friday, April 25th, 2025 at 4:00 pm:

"Protein and Ligand Discovery on a Global Scale"
Kavli Auditorium, 2nd Floor, Tata Hall
UC San Diego

Refreshments at 3:30pm both days.
No RSVP necessary.

Host: Neal Devaraj, Ph.D.
Contact: Jessica Ghio, jghio@ucsd.edu

From the speaker:
Advances in DNA sequencing have greatly increased our understanding of the genetic basis of human disease. However, many of human genes encode proteins that remain uncharacterized and lack selective small-molecule probes. To address these problems, we have introduced activity-based protein profiling (ABPP), a chemical proteomic technology that globally profiles the functional state and small molecule interactions of proteins in native biological systems.

In the first lecture, I will introduce the ABPP technology, review its origins rooted in active site-directed chemistry for the functional characterization of enzymes, and describe applications that include the chemical annotation of novel enzyme families and the discovery of inhibitors of enzymes that regulate important signaling pathways in the nervous system and cancer.

In the second lecture, I will describe how our lab is extending the principles of ABPP beyond the active sites of enzymes to construct global covalent small molecule interaction (or ligandability) maps of human cells and how this information can guide the discovery of first-in-class chemical probes for disease-relevant proteins. Key themes will include: 1) the importance of assaying proteins in endogenous environments to realize their full small molecule interaction potential; 2) the capacity of covalent chemistry coupled with ABPP to extend the druggability of the proteome to reach historically challenging target families like adaptor/scaffolding proteins and DNA/RNA-binding proteins; and 3) the remarkably diverse ways that allosteric small molecules can regulate protein function in cells.