Department: Surgery, University of Toronto
The focus of my research program is to develop a better understanding of the molecular pathways underlying the initiation and maintenance of colorectal cancers (CRCs). It is well established that cells within any given tumour display both functional and phenotypic heterogeneity. Experimental work over the past 50 years has also shown that not all cancer cells are created equal with respect to their ability to drive tumour growth; however, the biological basis for this observation remains to be fully elucidated. Our interest is to identify the molecular pathways responsible for driving tumour growth in the subset of CRC cells enriched for tumour-initiating capacity, also referred to as colorectal cancer-initiating cells (CC-ICs). Through identifying and characterizing the relevant molecular pathways we will also begin to understand the factors capable of modulating these survival pathways. One method we are using to better understand the survival mechanisms used by CC-ICs is through studying the molecular pathways they utilize to evade current chemotherapeutic strategies. By using functional genomic strategies to study CC-ICs, in the context of current chemotherapeutic agents, we are developing a better appreciation for the molecular pathways CC-ICs upregulate when exposed to standard of care chemotherapeutic agents. To better understand the factors driving CRC initiation we have commensed studies looking at a potential role for commensal bacterial flora in the intestinal tract. Our ability to isolate intracellular bacteria from approximately one half of CRC samples derived from both patients and xenografts has led us to question whether these bacteria are playing a role in driving tumour initiation and/or maintenance. The existence of intracellular bacteria in CRC samples is well established, the question that remains to be answered is whether their presence is functionally relevant. We are interested in determining if commensal bacteria have a role in generating and maintaining CRCs and more specifically, CC-ICs.