Cancer occurs when a single cell acquires multiple mutations that result in uncontrolled growth and survival. The tumour cell becomes addicted to these mutations and their activated signalling pathways. Our goal is to understand, exploit and target these tumour-specific vulnerabilities. Our ideas are simple and relevant, and our approach is novel and achievable. We focus on two major areas of research.

Regulation and function of the MYC oncogene. Myc is deregulated in >50% of human cancers and functions as a regulator of gene transcription. We are identifying the target genes regulated by Myc, the cofactors recruited by Myc and the post-translational modifications regulating these processes. Targeting Myc’s potent transforming activity through the development of novel inhibitors is a major
area of investigation. To achieve these goals we use state of the art technologies, including BioID, high-throughput functional analyses, ChIP-seq as well as RNA-seq, and have established several tissue culture and animal models for our work, including leukemia, neuroblastoma and breast cancers. Most recently, we have identified the first Myc-protein interactome and discovered novel regulatory mechanisms critical for Myc to drive cancer initiation and progression.

Exploiting tumour metabolism and statins as anti-cancer agents. Statins are a family of drugs used routinely in the control of hypercholesterolemia that we and others, have shown can trigger tumour-specific cell death. Statins block the rate-limiting enzyme of the mevalonate pathway, which is a basic biochemical pathway essential for cellular metabolism. Because statins are an approved drug for use in humans, we can immediately fast-track statins to impact patient care. To this end, our research goals are to understand why certain tumour-types are highly sensitive to statin-induced apoptosis and how best to use statins in combination treatment. Tumour types under study include leukemia, multiple myeloma, pancreatic, breast and prostate cancers, however, several others neoplasias are also potential targets. Most recently, we have discovered that blocking the restorative feedback response to statins potentiates statin action and this can be achieved by combining statins with another approved agent, dipyridamole. In addition to our research in the lab, we are collaborating with Clinical Scientists to conduct clinical trials to evaluate the efficacy and mechanism of statins as anti-cancer agents.