Bone and Mineral Physiology in Health and Disease

Osteoporosis and other bone diseases such as osteomalacia are significant causes of morbidity and mortality, and will of increasing importance as the population in United States and Europe ages. These diseases are due to abnormal calcium and phosphate metabolism and understanding how the concentrations of such ions are regulated and how bone and mineral homeostasis is regulated is central to the prevention of these diseases. The laboratory is interested in understanding how calcium and phosphate homeostasis in mammals is regulated and how it is altered in disease states. Several lines of investigation are being pursued:

  • The mechanism of action of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D, at the cellular and whole animal level is a major and long-standing area of investigation. The mechanisms by which vitamin D responsive genes are activated by the vitamin D receptor, and the role steroid hormone co-activator and co-repressors in vitamin D function, are being examined at the molecular and cellular level.
  • The pathophysiology of a new class of molecules, the "phosphatonins", which play a role in phosphate homeostasis is another area of investigation. The role of Wnt and secreted frizzled proteins in the control of renal phosphate reabsorption and bone remodeling is an active area of research. Other potentially phosphaturic molecules such as fibroblast growth factor 23 are also being studied.
  • The role of FGF 23 and sFRP-4 in tumor-associated syndromes is another area of research.