Endocrinology, Diabetes and Hypertension

Edward Brown, M.D.

Professor of Medicine

Dr. Brown's research focuses on how diverse cell types sense the extracellular calcium concentration (Ca2+o) and on the role of Ca2+o as an extracellular first messenger in health and disease. An adequate supply of calcium is critical for skeletal health, and calcium also serves as a key intracellular second messenger to regulate the functions of essentially all cells. More than a decade ago, Dr. Brown and colleagues cloned an extracellular calcium-sensing receptor (CaR), which proved that calcium could also serve as an extracellular first messenger. This receptor is present in many of the cells previously known to sense Ca2+o, including parathyroid, kidney, bone and intestinal cells, but is also expressed by numerous other cell types. Ongoing projects include studies of the receptor's roles in the various tissues expressing it, utilizing mouse models with knockout of the receptor in order to clarify how the CaR participates not only in calcium homeostasis but also in magnesium homeostasis as well as how it regulates the functions of diverse tissues uninvolved in mineral ion metabolism.

Selected References:

1. Tfelt-Hansen J, Chattopadhyay N, Yano S, Kanuparthi D, Rooney P, Schwarz RP, Brown EM.  Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. Endocrinology 2004;145:1211-1217.
2. Kifor O, McElduff A, LeBoff MS, Moore Jr. FD, Butters R, Gao P, Cantor TL, Kifor I, Brown EM.  Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism.  J Clin Endocrinol Metab 2004;89:548-556.
3. Yano S, Mentaverri R, Kanuparthi D, Bandyopadhyay S, Rivera A, Brown EM, Chattopadhyay N.  Functional expression of chemokine (-C-C) receptors in osteoblasts:  role of RANTES in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts.  Endocrinology 2005;146:2324-2335.
4. Tfelt-Hansen J, Ferreira A, Yano S, Kanuparthi D, Romero JR, Brown EM, Chattopadhyay N.  Calcium-sensing receptor activation induces nitric oxide production in H-500 leydig cancer cells.  Am J Physiol Endocrinol Metab 2005;288:E1206-E1213.
5. Tfelt-Hansen J, Yano S, MacLeod JR, Smajilovic S, Chattopadhyay N, Brown EM.  High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cells.  Growth Factors 2005;23:117-123.
6. Mallya SM, Gallagher JJ, Wild YK, Kifor O, Costa-Guda J, Saucier K, Brown EM.  Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism. Mol Endocrinol 2005, in press.
7. Tfelt-Hansen J, Ferreira A, Yano S, Kanuparthi D, Romero JR, Brown EM, Chattopadhyay N. Calcium-sensing receptor activation induces nitric oxide production in H-500 Leydig cancer cells. Am. J. Physiol Endocrinol. Metab. 288:E1206-1213, 2005.

 Contact Information:
(617) 732-5666
embrown@rics.bwh.harvard.edu