COBRE: USC: RETINOBLASTOMA GENE IN INFLAMMATION AND CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在这个实验室里我们有三个主要项目。第一个项目由刚从美国国立卫生研究院获得的校外资助（R21, 27.5万美元的直接费用，开始日期：2006年4月1日），包括检查人参和银杏对结肠炎和癌症中一氧化氮途径的影响。这是和迈克·沃戈维奇博士合作的。到目前为止，我们已经证明人参可以抑制一氧化氮的产生，这可能导致结肠癌的抑制，因为一氧化氮已经被证明是导致结肠癌的原因。第二个项目（R01待定）涉及检查与结肠炎相关的结肠癌中的pRb途径（Ying等人，cancer Research, 2005）。这个项目继续发展，我们已经证明一氧化氮是结肠炎中pRb通路失调的关键介质，并可能提供结肠癌的机制。我们的计划是在未来6个月内向高影响力期刊投稿一篇论文。最后，在与Mike Wyatt博士的合作下，我们正在检查碱基切除修复（BER）途径、慢性炎症和一氧化氮。在BER通路（AAG）中有一种特殊的糖基酶，其酪氨酸控制着AAG的功能。一氧化氮通过硝化酪氨酸残基，并改变目标蛋白的功能来靶向酪氨酸残基。这表明AAG是一氧化氮的靶标，这发生在慢性炎症和肿瘤发生中。未来的工作旨在继续收集所有未决和资助研究的数据。

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.