Colorectal stem cell transformation

Tissue stem cells are proposed to be the cell-of-origin of multiple cancer types. Determining the mechanisms important for stem cell transformation and tumour progression are critical for understanding these processes and guiding therapeutic development. My lab investigates stem cell transformation in the colon with the aim of identifying novel pathways that drive it. Growing evidence suggests alternative RNA splicing plays a key tumourigenic role and it dysregulation is common in cancer. We have recently identified a critical role for Rac1 during stem cell transformation, a gene that is hyperactivated via alternative splicing. We have also identified 100s of other aberrant splicing events during tumour initiation leading to the hypothesis that dysregulated RNA splicing is a critical mediator of colorectal stem cell transformation. We have 3 main questions we aim to answer: 1) What are the roles of oncogenic splicing factors altered in cancer, and the global changes in RNA splicing driven by them, during tumourigenesis? 2) With particular focus on Rac1b, what role does differential splicing play in cancer? 3) Can we identify other novel oncogenic pathways in the colon?