Faculty ProfilesWenhan Chang
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.
Recent Articles (10)
Hu DP, Ferro F, Yang F, Taylor AJ, Chang W, Miclau T, Marcucio RS, Bahney CS. Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes. Development. 2017 Jan 15; 144(2):221-234.
Kim W, Takyar FM, Swan K, Jeong J, VanHouten J, Sullivan CA, Dann P, Yu H, Fiaschi-Taesch N, Chang W, Wysolmerski J. Calcium-sensing receptor (CaSR) promotes breast cancer by stimulating intracrine actions of parathyroid hormone-related protein. Cancer Res. 2016 Jul 22.
Al-Dujaili SA, Koh AJ, Dang M, Mi X, Chang W, Ma PX, McCauley LK. Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone. J Cell Biochem. 2016 Jul; 117(7):1556-67.
Zhang M, Wang H, Zhang J, Zhang H, Yang H, Wan X, Jing L, Lu L, Liu X, Yu S, Chang W, Wang M. Unilateral anterior crossbite induces aberrant mineral deposition in degenerative temporomandibular cartilage in rats. Osteoarthritis Cartilage. 2016 May; 24(5):921-31.
Graca JA, Schepelmann M, Brennan SC, Reens J, Chang W, Yan P, Toka H, Riccardi D, Price SA. Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney. Am J Physiol Renal Physiol. 2016 Mar 15; 310(6):F518-33.
Schepelmann M, Yarova PL, Lopez-Fernandez I, Davies TS, Brennan SC, Edwards PJ, Aggarwal A, Graça J, Rietdorf K, Matchkov V, Fenton RA, Chang W, Krssak M, Stewart A, Broadley KJ, Ward DT, Price SA, Edwards DH, Kemp PJ, Riccardi D. The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. Am J Physiol Cell Physiol. 2016 Feb 1; 310(3):C193-204.
Wang T, Wang Y, Menendez A, Fong C, Babey M, Tahimic CG, Cheng Z, Li A, Chang W, Bikle DD. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing. J Bone Miner Res. 2015 Sep; 30(9):1572-84.