|Phone:||(519) 824-4120 x 54739|
|Office:||Department of Molecular and Cellular Biology|
University of Guelph
Research: The initial step of protein synthesis consists of the eukaryotic translation initiation factor 4E (eIF4E) binding to the 5’ cap of mRNAs. However, many cellular stresses repress cap-dependent translation to conserve energy by sequestering eIF4E. This raises a fundamental question in biology as to how proteins are synthesized during periods of cellular stress and eIF4E inhibition. Research in our laboratory will build upon the discovery that cells switch to an alternative cap-binding protein, eIF4E2, to synthesize the bulk of their proteins during periods of oxygen scarcity (hypoxia). What is the mechanism of activation? Which mRNAs are recruited to this machinery and how? How does it contribute to the expression of the cancer phenotype? We focus on cancer because as human tumors display considerable diversity in their genetic makeup, they share common physiological attributes such as a hypoxic microenvironment that contribute to the malignant phenotype. As oxygen only diffuses through a few layers of cells, the vast majority of cancer cells that populate a tumor are thought to be exposed to hypoxic conditions. Therefore, understanding how eIF4E2-dependent translation, a mechanism scarcely used by normal oxygenated cells, functions and contributes to the expression of the cancer phenotype will provide unique opportunities for cancer therapy.