The Centers of Biomedical Research Excellence (COBRE), together with support from Rhode Island Hospital and the Rhode Island community will enable us to develop the faculty and facilities needed to build a strong, interactive cancer research center focusing on the development of junior faculty pursuing research relevant to the cellular and molecular pathogenesis of cancer.
Description of Program Project Themes
Theme A - The significance of fetal proteins and phenotypes in cancer
Liver bile duct and colon carcinomas display a variety of proteins that are also expressed in fetal tissues. In some cases, the expression of these fetal proteins cease in normal adult tissues, a characteristic that makes these 3oncofetal2 proteins attractive targets for vaccines or immunotoxins. Recent studies have shown that a significant percentage of rat (ethionine induced) and human HCC express both oncofetal and ductal (oval cell) antigens in patterns that recapitulate developmental phenotypes, suggesting these HCC were derived from bipotent progenitor cells of ductal origin (Hixson et al, 2000, Exp Molec Path 68:152-169). Fetal-like stem cells also seem to be a primary target of carcinogens in the colon, most likely because the short half life of their progeny precludes progression to malignancy. Projects will investigate four different fetal proteins, MUC1, UCP2, TuAg1 (rat CD155), and LYRIC, the latter two discovered and identified as oncofetal antigens by COBRE faculty.
Theme B - Pathogenesis of Gastrointestinal Tumors
There are two subprojects relating to this theme. Weibiao Cao, MD will examine the role of cytokines and signal transduction processes in acid damage to epithelium produced by gastrointestinal reflux disease (GERD). His studies emphasize the role of proinflammatory mediators in the development of Barrett's esophagus known to progress to esophageal adenocarcinoma. Steven Moss, MD, is working on a subproject that emphasizes the role of H. pylori infection in gastric cancer and examines p27 kip1 expression and its interaction with other proteins in gastric antral cells in the context of persistent H. pylori infection. Such investigations have direct relevance to characterization of cell cycle changes that may occur during transformation of normal gastric cells to the malignant phenotype as a consequence of chronic exposure of the epithelium to H. pylori.
Theme C - Signal Transduction Mechanisms Relevant to Carcinogenesis
The central focus of the projects under this category is the identification and characterization of novel signal transduction mechanisms that contribute to the process of carcinogenesis.
Theme D - Role of RNA and DNA Viruses in Cancer
Pilot projects under this category will examine the role of RNA and DNA viruses in the pathogenesis of human tumors.
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