Integration of Oncogenic Networks in Cancer Phenotypes

癌症表型中致癌网络的整合

• 批准号: 7242419
• 负责人: JOSEPH R NEVINS
• 金额: $ 0.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7242419
• 关键词: bioinformatics; biological signal transduction; breast neoplasms; cell proliferation; computational biology; computer data analysis; data management; female; functional /structural genomics; guanine nucleotide binding protein; human tissue; laboratory mouse; laboratory rat; mathematical model; neoplasm /cancer relapse /recurrence; neoplastic growth; oncogenes; p53 gene /protein; protooncogene; tumor suppressor genes

The proposed Integrated Cancer Biology Program will combine the resources and expertise at Duke University, the Dana Farber Cancer Institute, UT Southwestern Medical Center, and the University of Southern California to focus on the development of data and computational tools to achieve an integrative and in-depth understanding of cell signaling pathways that are central to the control of cell proliferation and the oncogenic process. The work of the ICBP will focus on an integration of these oncogenic signaling pathways, representing a set of interconnected pathways including the Ras, Myc, and Rb-E2F pathway, that then also connect to the p53 response pathway. The activity of these pathways is fundamental and critical for the control of cells moving from a quiescent state, through G1 and into S phase, and that link the activity of the cellular proliferation process with the determination of cell fate. Moreover, the deregulation of these pathways is central to the development of human cancer. We aim to develop genomic-scale measures of gene expression and protein analysis to generate datasets whose analysis and interpretation will underlie the development of a comprehensive understanding of the complex regulatory networks that involves these pathways. Rather than developing a broad group of projects, we propose a highly focused program, involving a multi-disciplinary team of investigators, that will develop and apply novel methods of statistics and computation for modeling a set of highly lintegrated cellular pathways. By taking a very focused approach to these pathways, we believe we will be able to develop an in depth understanding of the activity and interaction within these pathways and use this as a paradigm for defining the tools for broader application to other aspects of cellular signaling. Importantly, we will also integrate this information in the study of human breast cancer, making use of the detailed datasets to inform predictive models of breast cancer recurrence. We believe this is a unique opportunity to bring together basic studies of oncogenic pathways with the study of human cancer in a way that will help to inform each process. These programs will also be the source of an integrated and multi-faceted training program that will serve as a training ground for young investigators at the interface of biology, genomics, and computational sciences. Finally, we will develop a web-based information management system to provide the tools for data access, utilization, and visualization of higher-order pathway and network data. The web-based system will also serve as a project management resource to link the activities of Center investigators as well as a mechanism for dissemination of data and computational tools to the scientific community.

拟议的综合癌症生物学计划将结合杜克大学，Dana Farber癌症研究所，UT西南医学中心和南加州大学的资源和专业知识，以专注于开发数据和计算工具，以实现对细胞信号通路的综合和深入了解，这是细胞增殖和致癌过程的核心。 ICBP的工作将集中 在这些致癌信号通路的集成中，代表一组包括RAS，MYC和RB-E2F途径在内的互连途径，然后还连接到p53响应途径。这些途径的活性对于控制从静态状态，通过G1到S相的细胞的控制至关重要，并且将细胞增殖过程的活性与细胞命运的确定联系起来。而且，放松管制 这些途径对于人类癌症的发展至关重要。我们旨在开发基因组表达和蛋白质分析的基因组规模衡量标准，以生成数据集，其分析和解释将是对涉及这些途径的复杂调节网络的全面理解的基础。我们没有开发一个广泛的项目，而是提出了一个非常专注的计划，涉及一个多学科团队 研究人员将开发并应用新颖的统计方法和计算方法来建模一组高度的细胞途径。通过对这些途径采用非常集中的方法，我们相信我们将能够深入了解这些途径中的活动和相互作用，并将其用作定义更广泛应用于细胞信号的其他方面的工具的范式。重要的是，我们还将整合 人类乳腺癌研究中的信息，利用详细的数据集为乳腺癌复发的预测模型提供信息。我们认为，这是一个独特的机会，将致癌途径的基础研究与人类癌症的研究结合在一起，以帮助为每个过程提供信息。这些计划还将成为一项综合且多方面的培训计划的来源，该计划将成为年轻调查员的培训理由 生物学，基因组学和计算科学的界面。最后，我们将开发一个基于Web的信息管理系统，以提供用于数据访问，利用和可视化高阶路径和网络数据的工具。基于Web的系统还将作为项目管理资源，以将中心研究人员的活动以及将数据和计算工具传播给科学界的机制。