Grant: Doctoral Research Award: Canada Graduate Scholarships

The human body is composed of many different cell types, all containing the same set of instructions, so then how are these different cells able to perform different functions? The field of epigenetics describes how environmental cues help turn genes 'on' and 'off' in different cells by changing the 3D structure of DNA without changing the core sequence, physically hiding or revealing genes. Similarly, immune cells can change their gene expression to respond to a perturbance in the body's environment (i.e. bacteria, virus, or tumour), and thus modify their DNA structure to respond to these threats. Invasive surgeries to remove tumours are followed by a window of significant immune suppression, permitting residual cancer cells to grow and spread. Our lab specifically, has studied the impaired function of natural killer (NK) cells in the postoperative period. NK cells are direct cancer-killing immune cells and can also help mount a larger, coordinated response against tumours by producing cancer-killing and immune-stimulating proteins; all these functions have been shown to be impaired postoperatively. While changes in the blood environment pre- and postoperatively have been characterized, the changes to the structure of the DNA have not been characterized. Here, we attempt to characterize how the changes in the environment after surgery affect the DNA structure, also known as epigenetic changes, and therefore why important tumour-killing genes are not being sufficiently expressed in the postoperative period. By gaining insight into these epigenetic changes, we will deduce a mechanism by which the postoperative environment causes impairment in the NK cell at the level of expression of these important tumour-killing genes. The knowledge of the mechanism will thus allow us to attempt to block the suppression of the NK cells to improve cancer cell killing postoperatively, and therefore reduce cancer recurrence.