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

After heart transplantation, recipient's immune system can recognize the transplanted heart, or cardiac allograft, as foreign and launch an immune response against it. This process can lead to acute cardiac rejection (ACR) episodes, which occurs in 20-50% of cardiac transplant patients at least once within the 1st year post-transplant and is detrimental to heart function. Although the exact mechanism behind ACR is not completely understood, it is widely accepted that two categories of immune response: cell- and antibody-mediated immunity, which involve white blood cells such as T and B lymphocytes, can play major roles in the rejection process. As well, studies have shown that unique changes in the blood of organ recipients (e.g. number of immune cells in the blood and/or their gene levels) can be observed during acute rejection, and the two may be correlated. Our laboratory has previously identified a set of genes that are present at significantly different levels in the blood of heart transplant recipients with and without ACR. While these genes are able to serve as biological indicators/biomarkers of ACR, they also provide windows of opportunities to gain insight into the mechanisms involved. For instance, one of the genes we found, called KLF4, has been associated with the regulation of T and B cells. However, its role in the context of ACR remains entirely unclear. In our proposed research, we will follow up on our previous findings and study the functions of the genes we have identified in a heart transplantation setting. We will also investigate the mechanisms through which genes like KLF4 can influence the immune cells and contribute to ACR. By distilling biological processes suggested by our previous observations, we can better understand the immune events underlying ACR. Ultimately, the results from this study may help uncover novel therapeutic targets to control or suppress ACR episodes and improve the health of heart transplant recipients.