Digestive System Neoplasms; Epithelial Cells; Gastrointestinal Diseases; Molecular Biology; Paneth Cells; Enterocytes; Gastrointestinal Tract
The plasma membrane of epithelial cells is divided into apical and basolateral domains that are structurally and functionally distinct. This polarity is crucial for the physiologic functions of epithelia. In development and during wound healing, epithelial cells can switch to a non-polarized, migratory phenotype. Disruptions in the control of cell polarity have been found to promote carcinogenesis. We study membrane polarity and proliferation in gastrointestinal epithelia. Specifically, we investigate the roles of scaffolding proteins called MAGUKs (membrane associated guanylate kinases) in 1) the assembly and basolateral targeting of signaling complexes in polarized cells, 2) tumor suppression, and 3) epithelial barrier maintenance in the intestine. Current projects include (a) analysis of MAGUK interactions with kinesin-family molecular motors, (b) characterization of CASK (a MAGUK) knockout mice with respect to intestinal repair and tumorigenesis, and (c) investigation of DLG5 (another MAGUK) function in the intestine and its role in inflammatory bowel disease.
- Walther, Z., and J. Sklar. 2011. Molecular Tumor Profiling for Prediction of Response to Anti-Cancer Therapies. Cancer J. 17:71-79.
- Walther, Z. and D.J. Jain. 2011. Molecular pathology of hepatic neoplasms: classification and clinical significance. Pathol. Res. Int. Apr 7:403929.
- Lozovatsky, L., Abayasekara, N., Piawah, S., and Walther, Z. 2009. CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity. Mol. Biol. Cell 20:4489-4499.
- Maday, S., Anderson, E., Chang, H.C., Shorter, J., Satoh, A., Sfakianos, J., Folsch, H., Anderson, J.M., Walther, Z., and Mellman, I. 2008. A PDZ-binding motif controls basolateral targeting of syndecan-1 along the biosynthetic pathway in polarized epithelial cells. Traffic 9:1915-24.
- Walther, Z. 2003. COX-2 and Angiogenesis in Gastric Cancer. J Clin Gastroenterol 37(1):4-6.
- Nix, S.L., Chishti, A.H., Anderson, J.M., and Walther, Z. 2000. hCASK and hDlg associate in epithelia, and their src homology 3 and guanylate kinase domains participate in both intramolecular and intermolecular interactions. J. Biol. Chem. 275:41192-41200.