We study the structure, pharmacology, and signaling of mammalian integral membrane receptors:
G protein-coupled receptors
GPCR family has over 700 members. They can sense extracellular signaling molecules with diverse chemical structures and then undergo complex conformational changes to activate or recruit intracellular effectors including heterotrimeric G proteins and β-arrestins. GPCRs mediate and regulate a broad spectrum of physiological and pathological processes. They 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 cell signaling assays to explore the molecular mechanisms underlying the signal transduction of 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.
Currently, we focus on two groups of GPCRs:
1) Chemotactic GPCRs that are involved in various inflammatory diseases and host defense against pathogens;
2) GPCRs for small-molecule and peptide neurotransmitters and neuromodulators that regulate locomotion, reward, cognition, appetite, and energy expenditure.