Calcium-sensing receptor – a G-protein-coupled receptor – signalling pathways in health and disease

The calcium-sensing receptor (CaSR), a G-protein-coupled receptor that is widely expressed, is critical for calcium homeostasis and also has non-calcitropic roles (development of neurons and lungs, cell fate, tumorigenesis and gastro-entero-pancreatic physiology). Mutations of the CaSR and associated proteins cause approximately 75 per cent of hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, and CaSR abnormalities may also affect glucose homeostasis. However, precise molecular mechanisms of CaSR signalling and trafficking, and their calcitropic and non-calcitropic roles, remain to be elucidated. During this award, Professor Thakker aims to characterise CaSR signalling and trafficking pathways and facilitate translational research. These studies also aim to provide diagnostic and therapeutic advances for patients with calcitropic disorders (eg renal and metabolic diseases associated with kidney stones) and non-calcitropic disorders (eg diabetes mellitus).