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NCIRE-The Veterans Health Research Institute is the leading private nonprofit institute devoted to Veterans health research in the United States. Our mission is to advance Veterans health through research.

We support the work of some of the nation's foremost physicians and scientists at the San Francisco Veterans Affairs Medical Center, the premier biomedical research facility in the VA system. All have faculty appointments at the University of California, San Francisco, which has its own proud traditions of research and patient care. We also partner with the U.S. Department of Defense to support health research on behalf of our men and women in the Armed Forces.

Those who have served in uniform have given their best for their country. In return, we believe that they deserve nothing less than the best health care research we can provide.

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Dolores Shoback, MD

Staff Physician, Medical Service, SFVAMC
Professor of Medicine, UCSF

Email: dolores.shoback@ucsf.edu

Role of Calcium-Sensing Receptors in Bone and Mineral Metabolism

Dr. Shoback's laboratory is working on how extracellular calcium-sensing receptors (CaSRs) sense changes in the extracellular calcium in the serum and in the bone microenvironment to alter cellular functions.  These receptors play critical roles in parathyroid and kidney function that have been well-established through human, animal and cell-based studies.  Our group is investigating the role of this receptor in the control of parathyroid hormone (PTH) secretion in mouse models and the interactions between the vitamin D receptor (VDR) and its systemically and locally generated (within the parathyroid gland itself) ligand 1,25-dihydroxyvitamin D (1,25-D) in the control of parathyroid function, systemic calciotropic hormone secretion, and mineral balance.  Most of our work is in conditional and generalized knockout mouse models with selected work experiments in vitro in parathyroid gland organ culture and in cultured osteoblast and bone marrow stromal cells.  The CaSR is strongly expressed in multiple different populations of cells within bone including osteoblasts and osteoclasts.  We are using several osteoblast-specific Cre recombinase expressing mouse lines to selectively delete the CaSR from osteoblasts at different stages of differentiation to determine the role of this receptor in osteoblasts during the stages of bone formation and mineralization.  We are also investigating the role of CaSRs in chondrocytes and osteoblasts in long bone fracture healing in conditional mouse models.  Our work is based on the idea that calcium is released from bone mineral during resorption and remodeling and acts as a ligand or signaling molecule in this microenvironment to control key steps in differentiation and osteoblastic function.  Our work has shown a key role for the CaSR in bone-forming cells and we hope to demonstrate a role for this molecule in different stages of fracture repair.       

To see Dr. Shoback on Pub Med, click here.