Project Grant R35GM161509

This $431,750 Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) supports fundamental research into the cellular regulation of mutationally activated G proteins (Gα subunits). Awarded to Thomas Jefferson University (Sidney Kimmel Medical College) with a performance period from July 1, 2026 through March 31, 2031, the research investigates how G protein alpha subunits function independently of G protein-coupled receptors (GPCRs) when mutations render them constitutively active. This work is significant because somatic mutations in Gα subunits are implicated in human diseases, particularly cancer—notably in uveal melanoma, where mutated Gαq and Gα11 are identified in over 90% of patients and serve as oncogenic drivers.

The research seeks to enhance understanding of G protein signaling mechanisms both at the plasma membrane and at intracellular organelles such as endosomes and Golgi, with particular focus on how mutationally activated Gα subunits are regulated in cells. By elucidating the cellular function and regulation of mutant Gα proteins, this project will advance fundamental knowledge of G protein biology and contribute to the scientific foundation necessary for developing therapeutic interventions targeting G protein-driven malignancies and other disease contexts.