Cysteine-Modification Screening to Identify Functional and Druggable Sites in Cancer Dependencies

Damon Runyon - Mark Foundation Postdoctoral Fellow (2020-Present)

Haoxin Li, PhD, The Scripps Research Institute

Haoxin Li, PhD

Dr. Li is focused on global mapping of functional cysteines in the Achilles’ heel of cancer. The unique chemistry of cysteine makes it an attractive target for therapeutic development. However, it remains difficult to design small molecules that target key cysteines and manipulate protein functions. Dr. Li will address this major challenge by performing functional screens that reveal the essentiality of different cysteine residues found in cancer dependency proteins. This work will create a next generation of cysteine ligandability map with precise phenotypic annotation and may greatly accelerate the discovery of new cancer therapeutics.

published research

Li H, Ma T, Remsberg JR, Won SJ, DeMeester KE, Njomen E, Ogasawara D, Zhao KT, Huang TP, Lu B, Simon GM, Melillo B, Schreiber SL, Lykke-Andersen J, Liu DR, Cravatt BF. Assigning functionality to cysteines by base editing of cancer dependency genes. Nat Chem Biol. 2023.

Liu Z, Remsberg JR, Li H, Njomen E, DeMeester KE, Tao Y, Xia G, Hayward RE, Yoo M, Nguyen T, Simon GM, Schreiber SL, Melillo B, Cravatt BF. Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders. J Am Chem Soc. 2024.