Shmuel Muallem, Ph.D.
Molecular Physiology and Therapeutics Branch/Epithelial Signaling and Transport Section
Building 10, Room 1N112
10 Center Drive
Bethesda, MD 20892
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 study 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 (HCO3-) transporters in ductal fluid and HCO3- secretion, which is vital for the function and health of all secretory glands. Defective regulation of HCO3- secretion occurs in many epithelial diseases including Cystic Fibrosis, Sjogren's syndrome and acute and chronic pancreatitis. HCO3- 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 HCO3- secretion as a model.
- 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
Park S, Ahuja M, Kim MS, Brailoiu GC, Jha A, Zeng M, Baydyuk M, Wu LG, Wassif CA, Porter FD, Zerfas PM, Eckhaus MA, Brailoiu E, Shin DM, Muallem S. Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV. EMBO Rep. 2016;17(2):266-78.
Vachel L, Shcheynikov N, Yamazaki O, Fremder M, Ohana E, Son A, Shin DM, Yamazaki-Nakazawa A, Yang CR, Knepper MA, Muallem S. Modulation of Cl<sup>-</sup> signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT. Sci Signal. 2018;11(554).
Zeng M, Szymczak M, Ahuja M, Zheng C, Yin H, Swaim W, Chiorini JA, Bridges RJ, Muallem S. Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice. Gastroenterology. 2017;153(4):1148-1159.
Jha A, Chung WY, Vachel L, Maleth J, Lake S, Zhang G, Ahuja M, Muallem S. Anoctamin 8 tethers endoplasmic reticulum and plasma membrane for assembly of Ca<sup>2+</sup> signaling complexes at the ER/PM compartment. EMBO J. 2019;38(12).
Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M, Swaim W, Eckhaus M, Hoffman V, Cui Y, Xiao B, Worley PF, Muallem S. Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity. Cell Metab. 2017;25(3):635-646.
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This page was last updated on February 20th, 2018