Chief, Epithelial Signaling and Transport Section
NATIONAL INSTITUTES OF HEALTH/ NIDCR
Building 10, Room 1N112
10 Center Drive
Bethesda, MD 20892
Phone: (301) 402-0262
Fax: (301) 402-1064
- 1974 B.Sc. and 1976 M.Sc. degrees, Ben Gurion University, Beersheba, Israel
- 1981 Ph.D. degree, The Weizmann Institute of Science, Rehovot, Israel (biochemistry and physiology)
- Postdoctoral fellowship, 1981-1983 University of Cambridge, Cambridge, England and 1983-1985 University of California, Los Angeles
- Assistant Professor, 1985-1988, University of California, Los Angeles, Associate (1988) and Full Professor (1994) of physiology, University of Texas Southwestern Medical Center
- 2010, Senior Investigator and Chief, Epithelial Signaling and Transport Section, NIDCR
Our lab is interested in epithelial transport, especially in the area of exocrine physiology and the regulation of enzymes, fluid and electrolyte secretion by epithelial cells. We are studying calcium (Ca2+) signaling in secretory glands acinar and duct cells that secrete fluid and digestive enzymes. In particular we focus on the gating mechanism governing the opening and closing of the plasma membrane Ca2+ influx channels and their role in inflammatory autoimmune diseases such as acute pancreatitis that can lead to multisystem failure and Sjögren's syndrome, a disorder that affects the exocrine glands that produce saliva and tears.
We are also investigating bicarbonate (HCOӡ-) transporters in ductal HCOӡ- secretion, which is vital for the function and health of all secretory glands. Defective regulation of HCOӡ- secretion occurs in many epithelial diseases including Cystic Fibrosis, Sjögren's syndrome and acute and chronic pancreatitis. HCOӡ- facilitates solubilization of macromolecules in secreted biological fluids to prevent clogging of the ducts. We combine electrophysiological and imaging techniques with molecular and biochemical approaches to study the organization of Ca2+ signaling complexes in cellular microdomains and the molecular mechanism of synergism in biology using ductal fluid and HCOӡ- secretion as a model.
- Zeng W, Yuan JP, Kim MS, Choi YJ, Huang GN, Worley FP and Muallem S. STIM1 gates TRPC channels but not Orai1 by electrostatic interaction. Molecular Cell, 32:439-48, 2008.
- Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF and Shmuel Muallem. SOAR and the polybasic STIM1 domains gate and regulate the Orai channels. Nature Cell Biology, 11: 337-343, 2009.
- Yang D, Li Q, So I, Huang CL, Ando H, Mizutani A, Seki G, Mikoshiba K, Thomas PJ, Muallem S. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 121:956-965, 2011.
- Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S. Irbit Mediates Synergy Between Ca2+ and cAMP Signaling Pathways During Epithelial Transport in Mice. Gastroenterology, 145: 232-241, 2013.
- Jha A, Ahuja M, Maléth J, Moreno CM, Yuan JP, Kim MS and Muallem S. The STIM1 CTID domain determines access of SARAF to SOAR to regulate Orai1 channel function. The Journal of Cell Biology, 202(1):71-9, 2013.