Robert Nissenson, Ph.D.
	Control of Bone Formation by Osteoblast Signaling
	Email: Robert.Nissenson@ucsf.edu
Selected Publications | Complete Publications

Current research efforts in my laboratory are focused on the use of molecular and transgenic approaches to understand the influence of specific cellular signaling pathways on the differentiation and function of osteoblasts, the cells responsible for bone formation. One major area of interest is the molecular basis of signaling by the G protein-coupled receptor (GPCR) for parathyroid hormone (PTH) and PTH-related protein, factors with major effects on bone development and function. We are exploring how ligand binding alters the conformation of the receptor, leading to the activation of adenylate cyclase and phospholipase C. In addition, we are actively investigating the role of receptor phosphorylation and arrestin proteins in regulating receptor signaling and intracellular trafficking. Transgenic approaches are being used to explore the relationship between specific signaling pathways and bone formation and turnover in vivo. One approach is the targeted expression of designer GPCRs that exhibit controlled signaling through specific G protein pathways. Initial results using two such designer GPCRs indicate that Gs signaling in osteoblasts positively regulates a potent anabolic pathway. Work is ongoing to define the mechanism by which Gs signaling in osteoblasts promotes bone formation, and to evaluate the potential therapeutic application of this new knowledge to osteopenic disorders and to fracture healing. One potential mechanism by which Gs signaling may increase bone formation is by promoting canonical Wnt signaling and thereby accelerating the differentiation of osteoblast precursors. Mouse genetic models are being employed to examine the relationship between Gs signaling and canonical Wnt signaling in the control of bone formation.

Selected Publications

J Peng, M Bencsik, A Louie, W Lu, S Millard, P Nguyen, A Burghardt, S Majumdar, TJ Wronski, B Halloran, BR Conklin, RA Nissenson. Conditional expression of a Gi-coupled receptor in osteoblasts results in trabecular osteopenia. Endocrinology 149:1329-1337, 2008.

DT McCloskey, S Turcato, G-Y Wang, L Turnbull, B-Q Zhu, T Bambino, AP Nguyen, DH Lovett, RA Nissenson, JS Karliner, AJ Baker. Expression of a Gi-coupled receptor in the heart causes impaired Ca2+ handling, myofilament injury, and dilated cardiomyopathy. Am J Physiol 294:H205-212, 2008.

M Sode, AJ Burghardt, RA Nissenson, S Majumdar. Resolution dependence of the non-metric trabecular structure indices. Bone 42:728-736, 2008.

DG Gardner and RA Nissenson. Mechanisms of hormone action. In Basic and Clinical Endocrinology (DG Gardner and D Shoback, eds.) Lange Medical Books/McGraw Hill, New York, pp. 35-58, 2007.

J Huang, T Sakata, L Pfleger, M Bencsik, B Halloran, DD Bikle, RA Nissenson. PTH differentially regulates expression of RANKL and OPG. J Bone Min Res:19:235-244, 2004.

Information last updated April 2008