- PO1 CA130821 –
“Cellular and Molecular Mechanisms of Gastrointestinal Cancers"
The Program Project focuses on cancers of the foregut, hepatocellular, gastric and pancreatic that are difficult to treat due to late diagnosis and a few viable therapeutics. Our hypothesis is that disruption of TGF-beta tumor suppression leads to activation of the Wnt signaling pathway, CDK4, hTERT (telomerase) and E3 ligases that include PRAJA as well as other key proteins that are activated and, thus, could represent new therapeutic targets in gastrointestinal cancers. The program proposes to use animal models to test the hypothesis, as well as develop markers and new targeted therapeutics.
- RC2 AA019392 -
“TLR4 and TGF-beta interactions in HCC induced by HCV and alcohol”
Hepatocellular carcinoma (HCC) develops synergistically in HCV-infected patients with alcoholism, and no treatments are available for this devastating complication. Based on our study results, we propose a ground-breaking hypothesis that enhanced TLR4 signaling and reciprocally suppressed TGF-β Signaling are in fact causally linked to render synergistic liver oncogenic signaling in the genesis of CSCs and liver tumor due to alcohol and HCV.
- RO1 CA106614 –
“Role of Elf/Smad4 in Gastrointestinal Cell Proliferation and Cell Cycle Progression”
The objective of this grant project is to study TGF-β as an important regulator of G1/S cell cycle progression of mammalian cells in culture to gain further insight into the role of elf/Smad4 in cell cycle regulation and neoplasia and to extend experiments to whole animal model systems by determining enhanced susceptibility of the elf+/-/Smad4+/- and Smad4+/- mice to the development of carcinomas following treatment with chemical carcinogens such as MNU and/or DMBA, and H. pylori VacA toxin, and carrying out experiments aimed at determining the molecular basis for enhanced susceptibility to neoplasia in the elf+/-/Smad4+/- and Smad4+/- mice.
- RO1 CA042857 –
“Metastatic Potential of Colorectal Carcinoma”
The aim of this grant project is to evaluate the role of Carcinoembryonic Antigen (CEA) in metastatic colon cancers, a disease which is difficult to treat due to late diagnosis and few viable therapeutics. Our primary goals is to develop a gene therapy approach to inhibiting expression of CEA by a Murine Stem Cell Virus-delivered ribozyme or gene silencing construct that is effective in vivo at inducing apoptosis and chemosensitivity.