Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy

摘要

The purpose of the research done has been to determine the regulation of the EGFR network and identify how manipulations of the network alter signal flow to bypass targeted inhibitions. The scope of the project is to understand the network and determine which molecules have to be targeted to inhibit tumor cell proliferation. We have completed the tasks of the grant proposal. In summary we have developed a quantitative phosphor-proteomic approach to measure changes in signaling in response to EGF in breast cancer cells. We have developed a quantitative model that incorporates the experimental data. Using this model we studied the signaling dynamics. We also manipulated specific nodes in the network and measured changes in the signal flow. Using this data in the model we determined feedback loops that are present in the cell. Using the developed model we predicted what combinations have to targeted to overcome feedback bypass of targets. These predictions were tested experimentally. The results from our work has been published in different parts in 5 publications. The DOD proposal has also allowed us to obtain a NIH R01 grant.