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Edward Meigs Brown
Senior Physician, Brigham and Women's Hospital
Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
75 Francis Street
Boston, MA 02115

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Research Narrative:

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 a critical for skeletal health, and calcium also serves as a key intracellular second messenger to regulate the function of essentially all cells. More than a decade ago, Dr. Brown cloned an extracellular calcium-sensing receptor (CaR), which proved that calcium could also serve as an extracellular messenger. This receptor is present in many of the cells that sense Ca2+ but relevant to this training program are kidney cells, vascular tissue and cells within the brain. Ongoing projects include studies of the receptor's role in the various tissues expressing it, including pursuit of his intriguing recent findings suggesting that the CaR, MR and ANGII type 1 receptor are co-localized with caveolin 1 in vascular smooth muscle and endothelial cells with unclear functional significance.

Investigative Interests: Calcium, Calcium-sensing receptor, Autoimmunity, Activating Mutation, Inactivating Mutation

Publications (Pulled from Harvard Catalyst Profiles):

1. Aggarwal A, Prinz-Wohlgenannt M, Gröschel C, Tennakoon S, Meshcheryakova A, Chang W, Brown EM, Mechtcheriakova D, Kállay E. The calcium-sensing receptor suppresses epithelial-to-mesenchymal transition and stem cell- like phenotype in the colon. Mol Cancer. 2015 Mar 18; 14:61.

2. Aggarwal A, Prinz-Wohlgenannt M, Tennakoon S, Höbaus J, Boudot C, Mentaverri R, Brown EM, Baumgartner-Parzer S, Kállay E. The calcium-sensing receptor: A promising target for prevention of colorectal cancer. Biochim Biophys Acta. 2015 Sep; 1853(9):2158-67.

3. Zhang C, Miller CL, Brown EM, Yang JJ. The calcium sensing receptor: from calcium sensing to signaling. Sci China Life Sci. 2015 Jan; 58(1):14-27.

4. Zhang C, Mulpuri N, Hannan FM, Nesbit MA, Thakker RV, Hamelberg D, Brown EM, Yang JJ. Role of Ca2+ and L-Phe in regulating functional cooperativity of disease-associated "toggle" calcium-sensing receptor mutations. PLoS One. 2014; 9(11):e113622.

5. Zhang C, Zhuo Y, Moniz HA, Wang S, Moremen KW, Prestegard JH, Brown EM, Yang JJ. Direct determination of multiple ligand interactions with the extracellular domain of the calcium-sensing receptor. J Biol Chem. 2014 Nov 28; 289(48):33529-42.

6. Zhang C, Huang Y, Jiang Y, Mulpuri N, Wei L, Hamelberg D, Brown EM, Yang JJ. Identification of an L-phenylalanine binding site enhancing the cooperative responses of the calcium-sensing receptor to calcium. J Biol Chem. 2014 Feb 21; 289(8):5296-309.

7. Jiang JY, Nagaraju M, Meyer RC, Zhang L, Hamelberg D, Hall RA, Brown EM, Conn PJ, Yang JJ. Extracellular calcium modulates actions of orthosteric and allosteric ligands on metabotropic glutamate receptor 1a. J Biol Chem. 2014 Jan 17; 289(3):1649-61.

8. O'Seaghdha CM, Wu H, Yang Q, Kapur K, Guessous I, Zuber AM, Köttgen A, Stoudmann C, Teumer A, Kutalik Z, Mangino M, Dehghan A, Zhang W, Eiriksdottir G, Li G, Tanaka T, Portas L, Lopez LM, Hayward C, Lohman K, Matsuda K, Padmanabhan S, Firsov D, Sorice R, Ulivi S, Brockhaus AC, Kleber ME, Mahajan A, Ernst FD, Gudnason V, Launer LJ, Mace A, Boerwinckle E, Arking DE, Tanikawa C, Nakamura Y, Brown MJ, Gaspoz JM, Theler JM, Siscovick DS, Psaty BM, Bergmann S, Vollenweider P, Vitart V, Wright AF, Zemunik T, Boban M, Kolcic I, Navarro P, Brown EM, Estrada K, Ding J, Harris TB, Bandinelli S, Hernandez D, Singleton AB, Girotto G, Ruggiero D, d'Adamo AP, Robino A, Meitinger T, Meisinger C, Davies G, Starr JM, Chambers JC, Boehm BO, Winkelmann BR, Huang J, Murgia F, Wild SH, Campbell H, Morris AP, Franco OH, Hofman A, Uitterlinden AG, Rivadeneira F, Völker U, Hannemann A, Biffar R, Hoffmann W, Shin SY, Lescuyer P, Henry H, Schurmann C, Munroe PB, Gasparini P, Pirastu N, Ciullo M, Gieger C, März W, Lind L, Spector TD, Smith AV, Rudan I, Wilson JF, Polasek O, Deary IJ, Pirastu M, Ferrucci L, Liu Y, Kestenbaum B, Kooner JS, Witteman JC, Nauck M, Kao WH, Wallaschofski H, Bonny O, Fox CS, Bochud M. Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations. PLoS Genet. 2013; 9(9):e1003796.

9. Kuo E, Kemp EH, Sandhu HK, Brown EM, Weetman AP, Huang CL. Acquired hypocalciuric hypercalcemia in a patient with CKD. Am J Kidney Dis. 2013 Dec; 62(6):1151-4.

10. Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J. Mammary-specific ablation of the calcium-sensing receptor during lactation alters maternal calcium metabolism, milk calcium transport, and neonatal calcium accrual. Endocrinology. 2013 Sep; 154(9):3031-42.