COBRE FOR SIGNAL TRANSDUCTION AND CANCER

描述(由申请人提供)：信号转导是 对肿瘤细胞生长、转移及其分子基础的认识 癌症对治疗的反应。随着蛋白质组学的到来，未来的癌症 治疗策略可以针对特定的信号通路量身定做 对于个人来说，基于个人的肿瘤？S的遗传背景。因此， 有可能开发新的辅助疗法，并将其用于 针对信号差异表达的现有治疗方案 预测为无反应或不良反应的患者中的蛋白质。我们的整体 研究目标是确定细胞信号蛋白中的分子变化 发生在癌症中，并针对这些蛋白质或基因变化 开发新的治疗方法。项目1：将介绍PI的角色 3-激酶介导的血管生成信号转导及新基因的鉴定 下游信号蛋白作为抗血管生成治疗的靶点。项目 #2：将讨论控制中性粒细胞的信号转导途径 激活以及这些信号在癌症患者中可能有何不同 接受了血液和骨髓移植。项目#3：将检查如何 细胞信号诱导DNA修复酶的表达和激活 卵巢癌，特别强调血管生成。项目#4：Will 细胞色素P450-1A1和-1A2亚型在肿瘤发生中的作用 并将使用分子建模技术来设计新的抑制剂 可以防止环境污染物代谢成致癌物质。 项目5：建议为蛋白质组设计新的微流控方法 从小样本中快速评估蛋白质表达的分析 用来辨认身份。这些分子变化中的每一个都将被分析为 预后、诊断、治疗和结果的指标，并可能揭示 治疗对传统疗法反应不佳的患者的策略。 这些项目将由初级教员领导，他们将由一名 行政核心。为了支持这些研究工作，有两个核心设施 还提出了用于荧光激活细胞分选器/细胞分离器(FACS)的 和质谱学。此外，SIGNAL领域的教师招聘 转导和癌症也被提出，这将扩大临界质量 研究癌症信号转导的癌症研究科学家 鼓励更大的协作努力。我们的长期目标是创造一个 强大的基础科学核心，将支持癌症研究/教育 西弗吉尼亚及周边阿巴拉契亚地区居民的临床治疗 区域。

DESCRIPTION (provided by applicant): Signal transduction is central to the understanding of cancer cell growth, metastasis and the molecular basis of cancer response to therapy. With the advent of proteomics, future cancer treatment strategies could be tailored to target specific signaling pathways for an individual, based on an individual tumor?s genetic background. Thus, it is possible that new adjuvant therapies can be developed and used with existing treatment regimens to target differential expression of signaling proteins in patients predicted to be non- or poor responders. Our overall research goal is to identify molecular changes in cell signaling proteins that occur in cancer and target these proteins or genetic changes for the development of new therapies. Project #1: will address the role of PI 3-kinase mediated signaling in angiogenesis and the identification of novel downstream signaling proteins as targets for anti-angiogenic therapy. Project #2: will address the signal transduction pathways that govern neutrophil activation and how these signals might differ in cancer patients who have undergone blood and marrow transplantation. Project #3: will examine how cellular signals induce expression and activation of DNA repair enzymes in ovarian cancer with a special emphasis on angiogenesis. Project #4: will address the role of cytochrome P450-1A1 and -1A2 isoforms in carcinogenesis and will use molecular modeling techniques to design novel inhibitors that could prevent metabolism of environmental pollutants into carcinogens. Project #5: proposes to design new microfluidic methods for proteomic analysis that will rapidly evaluate protein expression from small sample sizes for identification. Each of these molecular changes will be analyzed as indicators for prognosis, diagnosis, treatment and outcome and may reveal a strategy for treating patients who respond poorly to conventional therapies. These projects will be led by junior faculty, who will be mentored by an administrative core. To support these research efforts, two core facilities are also proposed for fluorescence activated cell sorter/cell separator (FACS) and mass spectrometry. In addition, faculty recruitment in the area of signal transduction and cancer are also proposed, which will expand the critical mass of cancer research scientist who study signal transduction in cancer and encourage greater collaborative efforts. Our long term goal is to create a strong basic science core that will support cancer research/education and clinical treatment for the citizens of WV and the surrounding Appalachia region.