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Tumour Angiogenesis and Apoptosis

My lab has a broad interest in identifying molecular pathways that limit tumour growth and delineating the mechanisms by which they become subverted in cancer. Towards this goal, we are studying two distinct processes.

A. The Role of the p53 Tumour Suppressor in Inhibiting Angiogenesis.
Angiogenesis, the process by which new blood vessels are formed, is an absolute requirement for tumour formation. One of our interests is understanding how tumors become vascularized and the mechanisms that can limit this process. Our focus is on the p53 tumour suppressor pathway and how it is able to inhibit angiogenesis. The p53 gene is mutated in half of all human cancers and at least part of its tumour suppression activity stems from inhibiting tumour vascularization. Angiogenesis is regulated through a balance of factors that either promote or inhibit vascularization. Studies from our group demonstrated that p53 stimulates the production of the potent angiogenesis inhibitors Endostatin and Tumstatin. Projects in the lab include the identification of novel p53-induced angiogenesis inhibitors and defining how such factors work.

B. Viral Mechanisms of Tumour Cell Destruction.
A variety of animal viruses have the ability to kill cancer cells while leaving normal cells unaffected. Thus, discovering the mechanisms by which these viruses destroy cancer cells could potentially lead to novel pathways that can be exploited for therapy. We use the viral protein Apoptin from Chicken Anemia Virus as a model for understanding tumour-specific cell death. The Apoptin protein has the ability to induce cell cycle arrest and p53-independent apoptosis specifically in cancer cells. We demonstrated that Apoptin interacts with and inhibits a large protein complex called the Anaphase Promoting Complex/Cyclosome (APC/C). The APC/C is absolutely required for cells to progress through mitosis and been shown to be a cellular target of several human viruses including HTLV, Adenovirus and Papillomavirus. Projects in the lab seek to determine why the APC/C seems to be a general target of such a diverse range of viruses and how inhibition of this complex can lead to specific destruction of cancer cells.