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Modeling and measuring growth factor pathways

We hope to fundamentally advance our understanding of growth factor signaling mediated by the set of six interacting ErbB1-4, IGF-1 and cMet receptors. First, we are working to create an ErbB model that is as fully calibrated against experimental data as possible by increasing the number of data points, directly measuring initial concentrations of proteins, and challenging the system through RNAi, protein overexpression, and small molecule inhibition. Second, we aim to understand why the dynamics of cell signaling are so variable from one cell type to the next. For this project, we study human breast cancer lines not only because of the importance of breast cancer as a disease but because a set of lines has been extensively characterized at a genomic level and relationships to primary tumor types established. We anticipate that our systems-based approach will provide insights for cancer biology and therapeutics. Finally, we are mapping, at sub-cellular resolution, the spatial and temporal relationships between the components of the ErbB activation process. We will then use this data to calibrate detailed kinetic models and thereby explore mechanisms by which spatio-temporally restricted “preprocessing” of signals in the plasma membrane can drive cell morphological outputs such as cell migration.

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This page last modified on September 11th, 2009