Grant: CIHR Fellowship

Cancer is a devastating disease that is the leading cause of death in Canada. However, how cancers develop and evolve is poorly understood. An important causative event for many cancers is the scrambling of the structure of their chromosomes, a process known as chromothripsis. Cells with scrambled chromosomes can acquire detrimental properties that can lead to cancer formation and evolution. Recent discoveries have shown that chromosome scrambling during cancer development often occurs because of defects in the architecture of the cellular structure that houses and protects chromosomes called the nucleus. My goal is to understand the casual link between abnormal nuclei and chromosome scrambling. I will take advantage of a newly developed technology to address this question. Existing technology allows for the manipulation of every gene in the human genome at the same time. With recent technological advances, the new approach enables us to combine this comprehensive gene manipulation with automated analysis of microscopic images of cells. This will allow me to determine which genes are required to generate nuclear abnormalities that scramble chromosomes to drive cancer development and the emergence of cancer therapy resistance. This research will provide important biological information on a disease that impacts the lives of millions, which is essential for the generation of new cancer treatments. In addition to cancer, my work is relevant to understanding developmental defects caused by chromosome scrambling in organisms as diverse as plants and humans. Together, the processes I aim to understand are general properties of cells that may contribute to the evolution of chromosomes in other contexts such as during the emergence of new species.