The goal of this laboratory is to define targets for cancer therapeutics by identifying alterations in signal transduction proteins and then translate these findings into important clinical tools, including one of the first effective peptide vaccines against cancer. The major type of cancer that we study is glioblastoma multiforme, the most common and devastating of the human brain tumors, but this work has also had implications for lung, breast, ovarian and prostate cancers.

Our research direction originated when we first identified a spontaneously occurring mutant EGF receptor in glioblastoma. Known as EGFRvIII (pronounced “E-G-F-R-v-three”), this molecule represents a deletion of exons 2 through 7 in the extracellular domain of the EGF receptor. This removes 273 amino acids and creates a novel glycine at the fusion junction. We have engaged in both very basic studies on the signal transduction pathways initiated by EGFRvIII, as well as translational work to create diagnostic tools and therapies around EGFRvIII.

Our basic science studies on understanding EGFRvIII signaling have led us to discover the Gab1 docking protein. Orignially discovered as a substrate for the EGF receptor, we and others have found that Gab1 is a substrate for numerous tyrosine kinase receptors, and in turn Gab1 recruits several proteins with SH2 domains. It is now clear that it is a vital link for multiple growth factor and cytokine pathways and has a role in diverse phenotypes such as cell survival, the cellular response to stress, and the cellular entry of parasites.