My group studies structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) as important cell membrane-embedded receptors. GPCR family has over 700 members. They transduce signals from extracellular signaling molecules to intracellular effectors through conformational changes within the receptors to mediate and regulate a broad spectrum of physiological and pathological processes. GPCRs have been heavily investigated in the pharmaceutical industry, and they constitute 30-40% of current drug targets. My lab utilizes structural biology approaches including X-ray crystallography and cryo-electron microscopy (cryo-EM) and functional studies including ligand-binding assays and cellular signaling assays to explore the molecular mechanisms underlying the signal transduction of GPCRs.
Currently, we focus on two groups of GPCRs: 1) the chemotactic GPCRs that recognize peptide and lipid chemoattractants involved in various inflammatory diseases; 2) the GPCRs for small-molecule and peptide neurotransmitters and neuromodulators involved in neurological and psychiatric disorders. We aim to reveal the structural basis for ligand recognition, activation, signaling, allosteric modulation and functional selectivity (biased signaling) of these GPCRs. In addition, we also perform structure-based drug design (SBDD) studies through collaboration and develop new GPCR antibodies as novel therapeutic candidates through combinatorial biology approaches such as yeast display.
Link to our publications: https://www.ncbi.nlm.nih.gov/myncbi/1Xqbv7vTlyh5w/bibliography/public/
https://www.czhanglab.org/