"Over the last several years me and my team have uncovered the reaction cycles that dynamically maintain the spatial organization of the Ras proto-oncogene products on cellular membranes. The quantitative microscopic imaging approaches in close iteration with computational systems dynamic analysis that we developed in the course of these studies were key to understand these reaction systems which were termed “spatial cycles”. Recent exciting results from my laboratory show that interference with spatial cycles, that normally maintain all major Ras isoforms on the plasma membrane, affects the signaling output from oncogenic Ras and thereby inhibits the growth and survival of KRas transformed murine pancreatic cancer cells. The purpose of the proposed multi-disciplinary project is to quantitatively assess in situ how the spatial organization of KRas affects the state of intracellular growth factor signaling networks and thereby maintains the phenotype of murine pancreatic cancer cells. A major objective that integrates the multiple levels of research in this proposal is whether and how the pharmacological inhibition of spatial cycles affects the growth of oncogenic KRas driven pancreatic tumors."