Quantitative models of receptor-mediated signaling.

Our lab is also involved in the development of mechanistic models of receptor-mediated signaling processes, with a special focus on models of EGFR phosphorylation and trafficking kinetics.  Such models are a useful vehicle for integrating our most recent quantitative cell biological measurements with existing structure-based models of EGFR function to develop new understand of EGFR regulation.  For example, our quantification of the kinetics of EGFR tyrosine dephosphorylation in different cellular compartments have been utilized to develop new experimentally testable predictions for the key determinants of the efficacies of different classes of EGFR-targeted therapeutics and to predict how differences in receptor dimerization schemes observed within the super-family of receptor tyrosine kinases may lead to different modes of signaling regulation for different types of receptors.  We are currently extending our models to develop predictive understanding of the ability of EGFR to regulate the persistence of multi-protein complexes of signaling proteins as a function of time and position within the cell.