Transgenic Core Facility, Faculty of Medicine

Our laboratory studies the roles of transcription factors and upstream signalling molecules in development and in intestinal homeostasis, including models of colorectal cancer. We have developed an understanding of an important gene regulatory network that is essential for normal mammalian development. Defects in this pathway are predicted to contribute to prevalent human congenital lesions, including neural tube defects and congenital heart defects, a prediction we are presently exploring. As is often the case, similar genetic pathways as those operating during development also appear to be re-deployed in cancer; in this case, we have evidence that the same transcription factors are implicated as potent tumour suppressors in a model of colorectal cancer. This is in agreement with observational studies in from human colorectal cancers, which show that this pathway is frequently modified in these tumours. An important outstanding question that we are addressing is how this pathway is altered in the genesis of cancer, and if this process is amenable to therapeutic intervention.