Project Grant R35GM164086

The National Institute of General Medical Sciences awarded The Regents of the University of California, San Francisco $551,000 on September 3, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop function-selective modulators of multifunctional hub proteins.

The research expands two programs: developing molecular glues to stabilize native protein-protein interactions and establishing technologies to study dynamic protein-interaction networks. The work focuses on selective manipulation of hub proteins that interact with dozens to thousands of partners, using drug-like molecules and protein engineering approaches. The principal investigator will develop molecular glues to stabilize native protein-protein interactions involving phosphoproteins bound to the 14-3-3 chaperone, including efforts to reform protein-protein interactions lost to interface mutations in rare diseases. The team will also stabilize client proteins bound to their chaperones, aiming to shift the proteostatic balance from protein folding to protein degradation. Deliverables include probes with new mechanisms of action, demonstration of a novel induced-protein-degradation mechanism, and insights into biophysical features supporting molecular glue discovery.

Performance occurs at UCSF in San Francisco, California, with a period of performance from September 3, 2026, through August 31, 2031. The award is structured as a Project Grant, the standard assistance type for investigator-initiated research under NIGMS's Biomedical Research program.