Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. 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). One of our main focuses will be 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 tumor cell phenotype will provide unique opportunities for cancer therapy.
Current areas of research include:
- Investigating how various cancers exploit eIF4E2-directed translation for tumorigenesis.
- Characterizing the eIF4E2 complex and understanding the mechanism of hypoxic cap-dependent translation initiation.
- Examining how the cap-dependent protein synthesis machinery adapts to diverse environmental cues.
We currently have positions open for those who are interested in studying the fundamental biological process of protein synthesis, how it adapts to stress, and how it is exploited by cancer. Our lab will provide you with the opportunity to present your work at international meetings and to gain expertise in many traditional and modern techniques in molecular biology and biochemistry including in vitro and in vivo tumor models. Interested candidates are invited to contact us.