Wenqing Shui, PhDAssociate Professor

The superfamily of G-protein-coupled receptors (GPCRs) play essential roles in diverse pathophysiological conditions and represent a most attractive family of therapeutic targets on which about 35% of marketed drugs act. Innumerable efforts have been made to discover novel ligands that can modulate the activity of specific GPCR targets or identify new potential drug targets from the GPCR superfamily for the treatment of various diseases. However, limitations of conventional techniques for GPCR ligand screening and functional proteomics highlight the need for more sensitive, selective and robust technologies that can accelerate GPCR drug discovery and functional elucidation.

The central theme of Shui group research is GPCR Proteomics and Ligand Discovery. My group is dedicated to developing versatile mass spectrometry (MS)-based approaches to be integrated with biochemical, structural, pharmacological and computational approaches for GPCR research in three specific directions:

I. GPCR ligand screen and drug discovery. We develop affinity MS techniques for high-throughput GPCR ligand screen, which generates ligands with new scaffolds and new activities to serve as chemical tools/probes for elucidating GPCR signaling mechanism or as potential leads for drug development.

II.Functional proteomics targeting GPCR proteins in the brain. Through profiling the transmembrane proteome, especially the GPCR family, in the brain with advanced proteomics technology, we aim to expand the understanding of membrane receptor organization and dynamics as well as accelerate the discovery of therapeutic targets for neurological disease treatment.

III. Structural proteomics to probe GPCR conformational dynamics. By developing structural MS approaches, we aim to map the conformational ensemble of GPCRs and their signaling complexes in solution or in cells, which could provide new insights into GPCR activation mechanisms and opportunities for the design of ligands targeting non-canonical GPCR states.