Center for Systematic Modeling of Cancer Development

本课题的总体目标是建立一个多尺度的乳腺癌研究模型平台，特别强调肿瘤启动细胞（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的生长调节剂。此外,

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.