Grant: Doctoral Research Award: Canada Graduate Scholarships

Patients with Type 1 Diabetes (T1D) have immune cells that wrongfully kill clusters of cells in the pancreas called islets, which are the body's sole producers of insulin. Without insulin, the body cannot regulate its blood sugar; unabsorbed sugar can cause vascular damage, leading to diseases of the nerves, eyes and heart. Currently, most patients painstakingly manage their T1D via constant blood glucose monitoring and injecting insulin. Recently, doctors have begun to treat some patients by transplanting them with healthy islets, abrogating the need for such meticulous monitoring and reducing the risk of developing other diseases. However, without intervention, the transplanted islets are quickly killed, either by the same immune cells that killed the patient's original islets, or by new immune cells that kill the transplant simply because it is from a different person. To prevent transplant loss, recipients must take immune-suppressing drugs. Although protecting the transplant, these drugs are dangerous because they also suppress the immune system's ability to fight infections and cancers. Our goal is to by-pass the need for these harmful drugs and instead, re-educate the immune system to accept the transplant. There is a subset of immune cells called regulatory T cells (Tregs) that naturally suppress harmful immune responses. We previously developed a method to genetically-modify Tregs to successfully prevent skin transplant rejection. I will assess whether these cells can also reduce islet transplant rejection in mice, and if in the process, they can also shut off the cells that originally caused T1D. My experiments are designed to give us important insight into how these cells work and thus how their use (dose, timing, etc.) can be optimized for clinical trials. My work will significantly contribute to our ability to use genetically engineered Tregs to minimize transplanted islet rejection, ultimately leading to better treatment options for patients with T1D.