Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Ovarian cancer is the most lethal gynecological cancer, taking the lives of 1% of Canadian women. While the cancer remains localized to the ovary, treatments are quite effective, but the spread of the disease throughout the body dramatically reduces efficacy. Unfortunately, most cases are diagnosed at late, metastatic stages. Understanding the molecular mechanisms ovarian cancer cells use to spread throughout the body may lead to new strategies to detect and therapeutically target these metastatic cells. It is widely-believed that in order to metastasize, cancer cells must undergo a process called an epithelial-to-mesenchymal transition (EMT). Within tumours, cancer cells are tightly anchored to each other (a characteristic of "epithelial" cells), but to metastasize, they remove these molecular anchors and activate genes that allow them to crawl around and burrow through tissues (characteristic of "mesenchymal" cells). This is also important for many normal processes, including embryo development and tissue repair. Despite being well-studied in these contexts, modern technologies have not been applied sufficiently to completely understand the molecular changes driving the EMT. The goal of the proposed project is to apply these technologies to map the molecular determinants of the EMT in ovarian cancer. First, we will expose ovarian cancer cells to a protein-transforming growth factor beta 1-that is a potent stimulator of an EMT. We will then use a technique called single-cell RNA sequencing to measure the activity of all genes in thousands of single cells after exposure, allowing us to map their response. After identifying which genes are activated or deactivated, we will use the DNA editing tool CRISPR-Cas9 to delete each of them to see which are critical for metastasis. This would provide a complete list of targetable genes to block metastasis and may also provide markers that could be used to predict the progression of a patient's cancer.