Research Projects

G protein-coupled receptors (GPCRs) are the largest and most diverse family of proteins in the human genome, playing a crucial role in regulating various cellular and physiological pathways. Understanding GPCR mediated signaling is essential in modern medicine, as half of marketed drugs are mediated through these receptors. One subfamily of GPCRs, sREB (super-conserved Receptors Expressed in Brain), consists of atypical orphan receptors with highly conserved sequences in vertebrates and predominantly expressed in the central nervous system. These receptors have been proposed to play important roles in various diseases, including atherosclerosis, autism, pancreatic β-cell insulin secretion and regulation, and schizophrenia. GPR173, or sREB3, is a highly conserved G protein coupled receptor, particularly expressed in the brain and ovaries, associated with the hypothalamic-pituitary-gonadal (HPG) reproductive axis. It is hypothesized to play a role in the pathogenesis of atherosclerosis, osteoblastic differentiation, and autoimmune diseases like systemic Lupus erythematous (sLE) in Chinese and European populations. However, considerable knowledge about the function and ligand of this receptor is largely unknown. Phoenixin (PNX) is one of the putatively known ligands, and Cholecystokinin (CCK) is established to be one of the ligands involved in excitatory circuit long-term potentiation. Understanding the role of GPR173 in physiological and pathogenic aspects makes it an interesting therapeutic target. The major aspect of the project involves gaining biological insights into new signaling pathways downstream of sREB3 using proteomics-based approaches, providing a framework for novel drug discovery.