David Stokoe, Ph.D.
Cancer is the result of the combined effects of a number of genetic mutations, some of which cause increased cellular proliferation, others of which cause increased cell survival. We are interested in examining mutations that contribute to dysregulation of signal transduction pathways involved in cell growth and survival. Two proteins which have been shown to be mutated in a large percentage of human tumors, are the small GTPase Ras (which becomes constitutively activated in cancer) and the dual protein and lipid phosphatase PTEN (which becomes inactivated in cancer). Mutation of these two proteins results in the activation of downstream signal transduction pathways including MAP kinase and protein kinase B, two serine/threonine protein kinases. We are examining the effects of inhibiting these pathways by a number of approaches in cell culture systems and in animal models of tumorigenesis, to determine whether these pathways can be manipulated in a therapeutic manner.