pH regulation of cell surface receptors

PROJECT NARRATIVE Changes in physiologic pH, particularly acidotic signals, accompany a variety of biological processes and clinical pathologies. The goal of our proposed research program is to pursue an in-depth understanding of how these pH signals regulate the biology and pharmacology of G protein-coupled receptors (GPCRs), the largest and most therapeutically targeted class of transmembrane receptors in the human genome. The three program areas of this proposal will identify pH-selective agonists, inhibitors, modulators, drugs, and conformationally-selective nanobody probes for regulating and studying numerous human GPCRs.