The research themes of this laboratory are translational in nature, and centre on gaining a better understanding of the basic pathophysiology of human malignancies in order to improve the management and treatment of patients with cancer.

Several projects in the laboratory are guided by the overarching hypothesis that dysregulated mRNA translation is essential to cellular transformation. This hypothesis is supported by prior work from our group and others which have demonstrated that the aberrant activation of several signaling pathways associated with the oncogenic state (including MAPK and PI3K/Akt) impinge on the cellular machinery that regulates both cap-dependent and cap–independent mRNA translation. These observations suggest that dysregulated translation contributes to cellular transformation via altering the expression of genes that control cellular proliferation and/or death. Importantly, these data indicate that therapeutic targeting of dysregulated translation is a valid strategy to test in the cancer clinic.

Specific projects in the laboratory include: investigating the role of cap-dependent and cap-independent translation in various human malignancies, the identification and development of small molecules which can target aberrant mRNA translation in cancer cells, and determining the identity of genes which are dysregulated at the level of translation. Other preclinical projects include the use of novel approaches to identify the molecular signature of drug resistance in primary human cancer tissues, as well as the genetic abnormalities that confer stem cell-like properties to human cancers, including the ability to self-renew. Finally, our group is also conducting an international Phase I study testing the feasibility and efficacy of targeting the mTOR kinase (a central regulator of eukaryotic mRNA translation) in patients with drug-resistant chronic myelogenous leukaemia.