Grant: CIHR Fellowship

Organ transplantation is the only curative treatment for organ failure; however, transplantation requires life-long immune-suppressive treatment, leaving patients at risk of life-threatening infection and cancer. An alternative to these drugs is to use a specific type of immune cell, called regulatory T-cells (Tregs), to dampen immune responses that lead to organ rejection. We developed a way to modify Tregs genetically, so they are activated by a protein found only on the transplanted organ. The protein acts as a homing beacon, drawing the injected Tregs to the organ and stimulating their immune suppressive machinery. We have shown that these engineered Tregs (made by modifying Tregs isolated from blood) protect skin transplants in mice, but the protection is transient. Other work in the lab has found that organ/tissue-resident Tregs show slightly different characteristics than blood Tregs. Therefore, we think that making engineered Tregs from cells in particular organs/tissues may function better in comparison to those made from cells in blood. Recently we developed a new mouse model that allows us to genetically modify Tregs within the mouse, enabling us to make transplant-protein-specific-Tregs. This model will allow us to isolate genetically engineered organ/tissue-resident Tregs. My research aims to utilize those genetically-engineered, tissue-resident Tregs and test their ability to protect transplanted organ. I will also study the immune suppression mechanisms of genetically-modified Tregs. If I find that the tissue-Tregs are better, I will explore what makes them superior to blood Tregs. I can then use this knowledge to further engineer Tregs to make them optimally effective as a therapeutic tool in preventing transplant rejection.