The epithelial tight junctions (TJs) form a barrier to the entry of allergens, toxins and pathogens across the epithelium into the interstitial tissue in various organ systems, including the gastrointestinal (GI) tract, liver, lung and kidney.  In the GI tract, the disruption of TJs and the loss of epithelial barrier function increase the intestinal permeability to injurious factors leading to inflammation and mucosal injury.  A significant body of evidence indicates that the disruption of TJ and increase in paracellular permeability play a crucial role in the pathogenesis of GI disorders, such as inflammatory bowel disease, alcoholic endotoxemia, infectious enterocolitis and celiac disease.

    The barrier function of the epithelium is provided by the sealing intercellular space by a specialized junctional complex called tight junction (TJ).  TJs are assembled by the organization of specific proteins. There are at least three types of transmembrane proteins, occludin, claudins and junction adhesion molecule.  In addition to these transmembrane proteins, TJs associate with numerous peripheral proteins, which include ZO-1, ZO-2, ZO-3, cingulin, 7H6 antigen, Rab3b, and symplekin.  Actin filaments are associated with the cytoplasmic plaque of the TJ, and are believed to stabilize the TJ assembly.  Growing body evidence indicates that the activities of intracellular signaling molecules such as protein kinases and G-proteins regulate the assembly and disassembly of TJs. 

    Studies in this laboratory are focused on understanding the molecular organization of TJs and its regulation by signaling pathways, especially those that involve protein kinases and protein phosphatases.  These studies are conducted in the context of TJ disruption in the pathogenesis of inflammatory bowel disease, alcoholic liver disease and colon cancer.  Our studies also address the mucosal protective factors, such as epidermal growth factor, L-glutamine and probiotics in the protection of TJs and for their potential therapeutic benefits in various GI diseases.