COBRE FOR SIGNAL TRANSDUCTION AND CANCER

COBRE 用于信号传导和癌症

• 批准号: 6530184
• 负责人: Daniel Charles Flynn
• 金额: $ 218.5万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-14 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530184
• 关键词: biological signal transduction; neoplasm /cancer; neoplasm /cancer genetics; neoplastic growth

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.

描述（由申请人提供）：信号转导对于 了解癌细胞生长、转移及其分子基础 癌症对治疗的反应。随着蛋白质组学的出现，未来的癌症 治疗策略可以针对特定的信号通路进行定制 对于个体，基于个体肿瘤的遗传背景。因此， 有可能开发和使用新的辅助疗法 针对信号差异表达的现有治疗方案 预测无反应或反应差的患者中的蛋白质。我们的整体 研究目标是确定细胞信号蛋白的分子变化 发生在癌症中并针对这些蛋白质或基因变化 新疗法的开发。项目#1：将解决 PI 的角色 3-激酶介导的血管生成信号传导及新型药物的鉴定 下游信号蛋白作为抗血管生成治疗的靶标。项目 #2：将解决控制中性粒细胞的信号转导途径 激活以及这些信号在患有癌症的癌症患者中可能有何不同 接受了血液和骨髓移植。项目#3：将研究如何 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：将 解决细胞色素 P450-1A1 和 -1A2 亚型在癌发生中的作用 并将使用分子建模技术来设计新型抑制剂 可以防止环境污染物代谢成致癌物质。 项目#5：建议设计新的蛋白质组微流体方法 可以快速评估小样本量蛋白质表达的分析 用于识别。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师领导，并由 行政核心。为了支持这些研究工作，两个核心设施 还建议用于荧光激活细胞分选仪/细胞分离器 (FACS) 和质谱分析。此外，信号领域的师资招聘 还提出了转导和癌症，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建一个 强大的基础科学核心将支持癌症研究/教育和 为西弗吉尼亚州及周边阿巴拉契亚地区的公民提供临床治疗 地区。