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Epithelial Signaling and Transport Section

Shmuel Muallem, Ph.D., Chief

Mission

The model shows the domains of the ER Ca2+ sensor STIM1 that gates the Ca2+ influx channels Orai and TRPC channels. The images show the restricted localization at of the Ca2+ release channel IP3 receptor type 3 and the Ca2+ influx channels Orai1 in the apical pole and the localization of STIM1 in both Orai1 expressing and Orai1-free cellular domains in the polarized pancreatic acinar cells.

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 pancreatic and salivary gland 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, Sjögren'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 coordination of ductal fluid and HCO3- secretion.

Measurement of pancreatic fluid secretion. The movie is of a sealed intralobular pancreatic duct in primary culture that is stimulated to secrete fluid into the duct lumen, as evident from expansion of the luminal space and enlargement of the duct.

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This page last updated: February 26, 2014