The superfamily of G-protein-coupled receptors (GPCRs) represents the largest class of cell surface receptors which play central roles in a variety of pathophysiological conditions. GPCRs are recognized as a prominent family of therapeutic targets upon which an estimated 30-40 % of marketed drugs act. Undoubtedly, innumerable efforts have been made in both industry and academia to identify novel ligands that can modulate the activity of a specified GPCR and characterize GPCR-ligand interactions at the molecular level.
However, the limitations of most commonly used techniques for GPCR ligand screening and current proteomics research highlights the need for more sensitive, efficient and robust technologies that can substantially facilitate GPCR drug discovery and cell signaling study. Our group is dedicated to developing versatile mass spectrometry-based methods which are integrated with biochemical, cell biology and structural biology approaches for GPCR research in three specific directions:
I. High-throughput identification of functional modulators for GPCR targets with affinity mass spectrometry technique. New GPCR ligands identified in our study could serve as critical chemical tools for elucidating GPCR signaling mechanism or potential leads for downstream drug development.
II. Discovery of brain disease-related biomarkers or potential drug targets from the GPCR superfamily with cutting-edge proteomics techniques. This new technique when coupled to other biological tools will largely expedite the identification of new GPCR targets involved in particular disease models as well as shed light on the structural basis of GPCR modulation and biased signaling.
III. Bioinformatics tool development for efficient mining of GPCR omics data to support GPCR ligand screening and target discovery.
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