My research investigates the roles of the extracellular Ca2+, insulin-like growth factor-1 (IGF1), parathyroid hormone (PTH), and vitamin D, and their respective receptors (CaSR, IGF1R, PTH1R, and VDR) in (1) controlling mineral homeostasis; (2) mediating skeletal development and facture healing; (3) regulating neuroendocrine functions; and (4) neuroprotection. We study mice with conditional knockout (KO) of genes encoding CaSR, IGF1, IGF1R, PTH1R, Cyp27b1, VDR, and their associated signaling molecules in parathyroid cells (PTC), intestinal epithelial cells, renal tubule cells, chondrocytes, bone cells, and/or neurons to determine their biological functions. These in vivo studies are complemented with in vitro cell/organ cultures of parathyroid cells/glands; primary intestinal and renal tubular cells and associated cell lines; primary chondrocyte, osteoblast, osteoclast, and related cell lines; and neurons to further delineate the underlying mechanisms. We perform union and nonunion bone fractures on the above KO mice and study the structural, biochemical, and biomechanics properties of the resulting callus to determine the functions of the CaSR, IGF1, IGF1R, PTH1R, Cyp27b1, VDR, and their associated signaling molecules in facture healing. Based on the above study, we are developing new pharmacological regimens for more robust skeletal anabolism to treat osteoporosis and repair bone. We also perform brain ischemia and traumatic brain injury protocols on the KO mice to assess the role of those molecules in the development of neuronal injury and to develop new therapies for neuroprotection against ischemia- and TBI-induced brain injury.
Dr. Chang is also the director of the SF-VAMC Bone Imaging Core facility.