Zenta  Walther, M.D., Ph.D.



Assistant Professor of Pathology


Department of Pathology
Yale University School of Medicine
P.O. Box 208023
310 Cedar St.
New Haven, CT 06520-8023

Office:
Lab:
Fax: (203) 737-1064

email: zenta.walther@yale.edu


Training:
GI Pathology Fellow, Yale University School of Medicine, July 2000-June 2001
Post-Doctoral Fellow, laboratory of Dr. J.M. Anderson, Division of Digestive
Disease, Dept. Internal Medicine, Yale University School of Medicine, 1997-2000
Resident, Anatomic Pathology, Yale University School of Medicine, 1995-1997
M.D. Cornell University Medical College, New York, NY,1995
Ph.D. (Cell Biology) Rockefeller University, New York, NY 1994
B.S. (Molecular Biophysics and Biochemistry)Yale University 1986

Expertise:
clinical - gastrointestinal and liver pathology
research - epithelial cell biology

Research Interests:
The plasma membrane of differentiated epithelial cells is divided into apical and basolateral domains that are biochemically, morphologically and functionally distinct. This polarity is crucial for the physiologic functions of mature epithelia. However, during wound healing and in embryogenesis, epithelial cells are able to switch to a non-polarized, more proliferative and migratory phenotype. Disruptions in the control of cell polarity have been found to promote carcinogenesis. We are interested in the cellular mechanisms by which plasma membrane polarity is generated and maintained. Specifically, we are investigating the role of cytoplasmic scaffolding proteins called MAGUKs (membrane associated guanylate kinases) in the assembly and targeting of signaling complexes to the basolateral membrane of polarized mammalian epithelia.
Members of the MAGUK scaffolding protein family have been implicated in basolateral targeting of growth factor receptors in C. elegans as well as tumor suppression in Drosophila and human breast cancer. We have used yeast two hybrid screening to identify novel binding partners of a MAGUK called CASK/LIN-2 and are characterizing these interactions. We have shown previously that in epithelial cells CASK is complexed with another MAGUK family member, hDlg (human discs large), which is a tumor suppressor in both fruitflies and humans. We are interested in the function of the CASK-hDlg complex and its relation to tumor suppression in the gastrointestinal tract. Finally, we are exploring the in vivo functions of CASK in the adult intestine and liver, using transgenic mice.

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Selected Publications:

Lozovatsky L, Abayasekara N, Piawah S and Walther Z. CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity. 2009. Mol Biol Cell (in press)

Walther Z and Topazian MD. 2009. Isospora cholangiopathy: case study with histologic characterization and molecular confirmation. Hum Pathol. 40:1342-6.

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.

Fanning, A.S., Little, B.P., Rahner, C., Utepbergenov, D., Walther, Z., and Anderson, J.M. 2007. The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization and scaffolding properties. Mol Biol Cell 18:721-731.

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.

Cohen, A.R., Woods, D.F., Marfatia, S.M., Walther, Z., Chishti, A.H., and Anderson, J.M. 1998. Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J Cell Biol 142:129-38.

Walther, Z., Vashishtha, M., and Hall, J.L. 1994. The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein. J Cell Biol 126:175-88.

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This page was last modified on: 08/28/2009