Calcium-sensing receptor (CaSR) - a G-protein coupled receptor (GPCR) - signalling pathways in health and disease. (360G-Wellcome-106995_Z_15_Z)

Calcium has critical roles in many body processes (e.g. nerve function, heart and muscle contraction, blood clotting, and hormone secretion) and is the major mineral in bone. The control of calcium in the body and plasma, involves a balance between the amounts that are absorbed from the gut, deposited into bone and other cells, and excreted from the kidney. Plasma calcium concentrations are chiefly regulated by parathyroid hormone, which acts on the kidneys and bones to alter calcium excretion a nd calcium release, respectively. Cells detect changes in plasma calcium by having on their surface, calcium-sensing receptors that relay signals to intracellular pathways, which effect appropriate responses. We will investigate the roles of the calcium-sensing receptor signalling pathways in regulating kidney function and secretion of the pancreatic hormone insulin, whose dysregulation results in common disorders of kidney stones and diabetes mellitus, respectively. We will study patients with such metabolic disorders, as well as cellular and in vivo models, to increase mechanistic insights about the calcium-sensing receptor in health and disease, and investigate compounds that modulate signalling by the calcium-sensing receptor. Thus, our research will elucidate the disease mechanisms and biology of the calcium-sensing receptor, and identify potential drugs for human disorders.