Overview
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.
Research Activities and Funding
ShEEP Request for SCANCO Medical VivaCT 80 preclinical micro-computed tomography (pCT) system
VAIS1BX003589
May 1, 2016 - Sept. 30, 2016 | Role: Principal Investigator
Combined PTH and Calcimimetic Therapy and Its Mechanisms for Osteoanabolism
NIH/NIAMS R01AR067291
Feb. 11, 2015 - Dec. 31, 2019 | Role: Principal Investigator
UCSF Core Center for Musculoskeletal Biology and Medicine
NIH/NIAMS [P30AR066262])http://grantome.com/search?q=P30AR066262)
July 1, 2014 - June 30, 2019 | Role: Co-Investigator
The Role of CaSR and GABA-B-R in Neuronal Responses to Ischemic Brain Injury
VA I01BX001960
April 1, 2013 - March 31, 2017 | Role: Principal Investigator
INTERACTIONS BETWEEN GABA B AND CA2+-SENSING RECEPTORS
NIH/NIAMS R21AR054441
March 6, 2007 - Feb. 28, 2010 | Role: Principal Investigator
Resolution of Stage-Specific Growth Plate Chondrocytes
NIH/NIAMS R21AR050662
Sept. 25, 2003 - June 30, 2006 | Role: Principal Investigator
CALCIUM-SENSING RECEPTORS AND GROWTH PLATE DEVELOPMENT
NIH/NIA R01AG021353
Feb. 15, 2002 - March 31, 2014 | Role: Principal Investigator