Lee S. Weinstein, M.D., Acting Chief
Sunita K. Agarwal, Ph.D.
Stephen J. Marx, M.D.
William F. Simonds, M.D.
The Metabolic Diseases Branch studies clinical disorders of calcium metabolism, in particular diseases related to the abnormal production or action of parathyroid hormone, a circulating factor that tightly regulates serum calcium levels. The branch’s research is primarily focused on two areas: (1) understanding the clinical genetics and pathogenesis of sporadic and familial forms of primary hyperparathyroidism (tumors of the parathyroid glands that oversecrete parathyroid hormone) and (2) understanding the pathogenesis of human disorders with abnormal hormone action due to defects in G protein signaling molecules and the cellular and physiological functions of G proteins.
The branch consists of three sections:
The Signal Transduction Section, headed by Lee S. Weinstein, studies the genetics and pathogenesis of parathyroid hormone resistance disorders (pseudohypoparathyroidism and Albright hereditary osteodystrophy) that are caused by genetic defects of a G protein involved in hormone signaling. The section also studies the role of these G proteins in other processes, particularly how they regulate energy balance (weight) and glucose metabolism. These studies may have important implications for basic understanding of the mechanisms underlying obesity and diabetes. Research in the section combines clinical studies with basic research utilizing various animal models.
The Genetics and Endocrinology Section, headed by Stephen J. Marx, studies the pathogenesis of multiple endocrine neoplasia type 1 (MEN1) and other causes of hormone-secreting tumors. Studies are done with affected patients and using molecular genetic methods. These efforts include searching for genes not previously implicated in endocrine tumors and studying the functions of these genes in normal and abnormal cells. This section also includes the Gene Regulation Unit, headed by Sunita K. Agarwal, which conducts basic research to elucidate the molecular processes responsible for normal and neoplastic growth and function of endocrine cells, such as the insulin-secreting pancreatic islet β cells. The unit’s current focus is on β cell differentiation factors and changes in cell cycle regulators and histone modifications within endocrine tumors.
The Endocrine Signaling and Oncogenesis Section, headed by William F. Simonds, studies the genetics and pathogenesis of familial forms of hyperparathyroidism and parathyroid cancer, including the biology of CDC73/HRPT2, a tumor suppressor gene whose inactivation has been implicated in parathyroid malignancy. In addition, the section is studying the biology of a unique brain and endocrine tissue-specific G protein complex (GΒ5-R7 RGS). These studies may have important implications for our basic understanding of neoplasia and neuroendocrine signaling.