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Yana Zavros, PhDAssistant Professor Department of Molecular and Cellular Physiology
Gastric cancer develops from long-term inflammation that is typically caused by the bacteria Helicobacter pylori (H. pylori). During the progression from inflammation to cancer, the stomach epithelium changes with evidence of disruption of normal gland morphology and differentiation and the recruitment of inflammatory cells. Although it is accepted that inflammation precedes these pre-neoplastic changes, the mechanism by which inflammation triggers the development of cancer is unknown. Sonic Hedgehog (Shh), a morphogen originally identified for its role in embryogenesis, is believed to regulate adult epithelial cell homeostasis. In fact, coincident with H. pylori infection is the loss of Shh expression and this would then be expected to result in loss of normal epithelial cell differentiation. Dr. Zavros’ laboratory is responsible for discovering that in the mammalian system Shh secretion from this acid-secreting single cell type has significant biological activity by regulating the differentiation of cell lineages and controlling gastric physiological function. Thus, the current focus of Dr. Zavros’ research is to define the mechanism by which Shh acts as a constituent of gastric epithelial cell homeostasis and disease.
Dr. Zavros collaborates collaborates with Drs. Hogan, Shroyer, Hoebe and Shull. Anticipated Core use: Integrative Morphology Core, Gene and Protein Expression Core, and Bioinformatics Core.
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Quantification of parietal, mucous neck, and zymogen cells in control and HKCre/ShhKO mice. (A) The number of parietal cells (H+,K+-ATPaseβ subunit), mucous neck cells (GSII), zymogen cells (IF), and dual-labeled GSII/IF cells in 8-month-old control and HKCre/ShhKO mice was counted. *P< .05 compared with the control animals. Immunofluorescence of (B) control and (C) HKCre/ShhKO mouse groups stained for IF (red) together with GSII (green). Merged images are shown. Colocalization is indicated in yellow. Figure from Gastroenterology, 2010;138:550-61, 561.e1-8.
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