? The overall aim of this project is to develop a new profiling technology that can be used to classify diseases such as cancer by the state of tyrosine phosphorylation.
The aim of this Phase I proposal is to develop and demonstrate the feasibility of a novel multicolor tyrosine phosphoprofiling technology that will define the dysregulated kinase state in the progression of cancer. Phosphorylation of proteins by protein tyrosine kinases generates cell signals that regulate cell proliferation and differentiation. The pattern of tyrosine phosphorylation in tumor cells, therefore, reflects the activity of tyrosine kinases and will be highly related to the tumor phenotype and path of disease progression. This technology that will be developed under this proposal has the potential to identify and define disease classifications that are independent of histology and which will reveal different phosphoprotein patterns that reflect the tumor's specific biology and microenvironment despite similar levels of expression of messenger RNA and unphosphorylated proteins. Such classifications will allow earlier and more specific disease diagnosis, provide better prognosis and ultimately be able to define the best therapy for a particular disease classification. In addition, this Phase I proposal will provide important tools that will enhance our understanding of the role of tyrosine phosphorylation in cancer and other diseases. ? ? ?
