Center for Systematic Modeling of Cancer Development

癌症发展系统建模中心

• 批准号: 8089854
• 负责人: STEPHEN TC WONG
• 金额: $ 12.17万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089854
• 关键词: Address; Bioinformatics; Breast Cancer Treatment; CD44 gene; Cancer Biology; Cancer Etiology; Cancer Model; Candidate Disease Gene; Cessation of life; Data; Data Analyses; Development; Environment; Enzymes; Mammary Neoplasms; Normal Cell; Pharmaceutical Preparations; Preclinical Drug Evaluation; Skin; Systemic Therapy; Systems Biology; cytotoxic; data mining; imaging modality; in vitro Assay; in vivo; tumorigenesis

The overall goal ofthis proposal is to build a multi-scale modeling platform for investigation ofthe breast cancer, with special emphasis on the roles of the tumor-initiating cells (TIC). This modeling platform will mainly consist of two closely related components: biological experiments and mathematical computational modeling. For the experiment component, we seek to use newly developed experimental and imaging methodologies to identify, localize, purify and characterize TIC. Further experiments will be designed to discover the spatial localization and movement, and specific changes in gene expression and cellular signaling of breast cancer TIC. Combined functional genomics and data mining strategies will allow us to characterize novel growth regulators. Further, our combined experimental and systems biology approach will allow us to evaluate responses to experimental therapeutics that may inhibit or kill TIC specifically in a manner not possible before. For the mathematical modeling component, we will develop bioinformatics and bio-imaging models to integrate and analyze the data generated from biological experiments, and make use ofthe information obtained from data analysis, biological knowledge to build in silico models to model TIC behavior, cancer cell apoptosis, cell migration, cycle and drug treatment response. Besides providing a basic framework for understanding the mechanism underlying breast cancer stem cell evolution, the models can also give birth to hypotheses or experimental design. More important, these models will allow one to predict the biological state under investigation and predict how the natural process will behave in various circumstances. Iterative feedback between these two components will refine our proposed platform further. The ultimate goal is an integrated modeling platform of breast cancer biology that can mimic in vivo processes faithfully enough to serve as a h5TDOthesis-generation and screening tool, and in the distant future, as a tool for evaluating clinical procedures and their expected outcomes.

该提案的总体目标是建立一个用于乳腺癌研究的多尺度建模平台，特别强调肿瘤起始细胞（TIC）的作用。该建模平台将主要由两个密切相关的部分组成：生物实验和数学计算建模。对于实验部分，我们寻求使用新开发的实验和成像方法来识别、定位、纯化和表征 TIC。进一步的实验将旨在发现乳腺癌TIC的空间定位和运动，以及基因表达和细胞信号传导的具体变化。结合功能基因组学和数据挖掘策略将使我们能够表征新型生长调节剂。更远， 我们的实验和系统生物学相结合的方法将使我们能够评估对实验疗法的反应，这些疗法可能以以前不可能的方式特异性地抑制或杀死 TIC。对于数学建模部分，我们将开发生物信息学和生物成像模型来整合和分析生物实验产生的数据，并利用数据分析和生物知识获得的信息建立计算机模型来模拟TIC行为、癌细胞细胞凋亡、细胞迁移、周期和药物治疗反应。除了提供理解乳腺癌干细胞进化机制的基本框架外，这些模型还可以产生假设或实验设计。更重要的是，这些模型将允许人们预测正在研究的生物状态，并预测自然过程在各种情况下将如何表现。这两个组件之间的迭代反馈将完善我们的 进一步提出平台。最终目标是建立一个乳腺癌生物学的集成建模平台，能够忠实地模拟体内过程，作为 h5TDO 论文生成和筛选工具，并在遥远的将来，作为评估临床程序及其预期结果的工具。