Grant: Doctoral Research Award: Canada Graduate Scholarships

Every year in Canada, over 2800 women are diagnosed with ovarian cancer, and over 60% of these women die of the disease. In a particular type of ovarian cancer (ovarian clear cell carcinoma), as many as 55% of patients tumours contain a mutation (an error in normal DNA) in a protein called ARID1A. ARID1A is a subunit of a larger protein complex that functions in the regulation of DNA organization within the cell, which affects a variety of cellular processes including the expression of genes into proteins. Recent research has suggested that loss of ARID1A in cancer leads to an increased rate of mutations over the course of a cell division (referred to as "genome instability"), which contributes to the progression of the disease. However, the exact mechanism by which ARID1A loss results in genome instability remains unclear. One process by which genome instability can arise is through improper pairing of RNA and DNA during the expression of genes into proteins, resulting in a hybrid structure called an "R-loop". Importantly, my results show that ARID1A loss in cancer cell lines leads to an increase in these R-loop structures, which also results in more DNA damage accumulation, contributing to genome instability. Moving forward, my goal is to uncover the mechanisms underlying how R-loops cause genome instability in ARID1A-deficient cells to better understand how mutations in ARID1A contribute to cancer progression. In parallel, I have implemented a large-scale screening approach within our lab to identify genes that become essential for cell survival when ARID1A is mutated. This will allow me to identify new therapeutic targets to selectively kill cancer cells and improve current treatments of ovarian cancers. Ultimately, my research will provide new knowledge on how ARID1A loss promotes cancer development and may lead to improved therapies.