Grant: Travel Awards - Institute Community Support

The vast majority of human genes undergo a process known as alternative splicing (AS), which leads to the production of multiple mRNA and protein isoforms from a single gene. Recent advances in next generation sequencing have revealed that tumours exhibit abnormal AS patterns compared to normal tissues and changes in splicing occur in genes involved in every step of the transformation process, including metabolism, apoptosis, cell cycle control, invasion and metastasis. Furthermore, mutations affecting splicing factors have been identified in many cancer types. Therefore, aberrant AS is increasingly recognised as a hallmark feature of cancer. However, the full landscape of AS events that control cell proliferation is not known. Accordingly, a major goal of biomedical research is to systematically determine the role of alternatively spliced exons in the context of cell proliferation and transformation. To address this goal, I have developed a novel CRISPR-based screening platform enabling for the first time the comprehensive identification of exons underlying cell proliferation. Initial application of this technology in neuroblastoma and leukemic cell lines has identified alternatively spliced exons that control cell fitness and proliferation. Remarkably, in addition to exons previously reported to underlie cell transformation, we also identified new candidate exons, many of which are located in genes linking extracellular environment to cellular responses and promoting cell growth. In conclusion, I have developed the first systematic approach for investigating the biological function of alternative exons impacting cellular fitness. My research is expected to provide novel insights into the mechanisms underlying tumorigenesis and holds promise for identifying novel cancer therapeutic targets, which will be of considerable benefit to Canadians.