Naomi R. Latorraca
Assistant Professor, Department of Biochemistry and Molecular Biophysics
B.A./B.S., University of Pittsburgh
Ph.D., Stanford University
The 800 human G protein–coupled receptors (GPCRs) represent molecular targets for various human diseases, from cognitive disorders to autoimmunity and cancer. In canonical GPCR signaling, diffusible ligands bind GPCRs to turn on signaling networks within the cell. GPCRs also interact with proteins on neighboring cell membranes to organize cellular contacts, but whether and how these interactions regulate GPCR signaling remains poorly understood. Our long-term objective is to harness such interactions to develop novel GPCR-targeted therapeutics, focusing on two questions: first, how do transcellular modulators alter the signaling profile of a GPCR and its sensitivity to known drugs? Second, how do adhesive forces at cellular interfaces modulate GPCR signaling? We monitor conformational changes in membrane-bound receptors using single-molecule fluorescence and integrate these measurements with physics-based simulations of receptor activation and signaling assays. Collectively, these data will identify new strategies and targets for modulating GPCR signaling in the lab and the clinic.