Mathematical modeling of proximal cellular signaling
Quantitative Phosphoproteomics, Bioinformatics, System Biology, Cellular Signaling, Signaling Networks, Receptor Tyrosine Kinases (RTKs), Fibroblast Growth Factor Receptor (FGFR) family
Receptor Tyrosine Kinases (RTKs) enable cells to respond to the extracellular environment and to decide whether to grow, differentiate or die. Growth factors binding to and activating RTKs control differentiation, proliferation, survival, and migration by initiating intracellular signaling cascades. However, how different ligands binding to the same receptor orchestrate the activation of specific signaling pathways and specific outputs (i.e. proliferation versus migration) over time is not understood.
MS-based quantitative phosphoproteomics is a powerful technology to monitor changes in the activation of signaling pathways by measuring phosphorylated peptides. Focusing on the family of FGFRs, which plays major roles during embryonic development and breast cancer (Dorey and Amaya, 2010; Fearon et al., 2013), we have demonstrated that signals controlling cell proliferation and cell migration are encoded by the ligands binding to FGFRs (Francavilla et al., 2009 and 2013). By combining quantitative phosphoproteomics with state-of-the-art systems biology analysis, mathematical modeling, and cellular assays, this project will test whether molecular determinants of cell proliferation and migration can be predicted in silico (Narushima et al., 2016). Therefore, this project will make a significant contribution to our understanding of how cellular decisions are generated and regulated.