COBRE: USC: RETINOBLASTOMA GENE IN INFLAMMATION AND CANCER

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have three main projects in this lab. The first, funded through an extramural grant just received from the NIH (R21, $275,000 direct costs, start date: 04/01/2006) involves examining the effects of Ginseng and Ginkgo on the nitric oxide pathway in colitis and cancer. This is in collaboration with Dr. Mike Wargovich. We have so far shown that Ginseng inhibits nitric oxide production, which may lead to an inhibition of colon cancer since nitric oxide has been shown to drive this disease. The second project (R01 pending) involves the examination of the pRb pathway in colon cancer associated with colitis (Ying et al., Cancer Research, 2005). This project continues to evolve, and we have shown that nitric oxide is a key mediator of pRb pathway dysregulation in colitis, and may provide a mechanism toward colon cancer. Our plan is to submit a paper to a high impact journal in the next 6 months. Finally, in collaboration with Dr. Mike Wyatt, we are examining the base excision repair (BER) pathway, chronic inflammation, and nitric oxide. A specific glycosylase in the BER pathway (AAG) has a tyrosine that controls AAG function. Nitric oxide species target tyrosine residues by nitrating them, and changing the function of the targeted protein. It is suggested that AAG is a target of nitric oxide and that this occurs in chronic inflammation and tumorigenesis. Future work is aimed at continuing collection of data for all pending and funded studies.