Grant: CIHR Fellowship

After an organ transplant, drugs that suppress the immune system are used to lower the risk of organ rejection. However, these drugs are toxic and do not eliminate organ rejection risk. Regulatory T cells (Tregs) are immune cells that prevent excessive inflammation, acting like a brake on the immune system. My goal is to use these Tregs as a therapy or a "living medicine" to regulate immune system responses. The hope is that Treg therapy will reduce the need for toxic immune-suppressing drugs after organ transplantation. Right now, Treg therapy must be used alongside standard immune-suppressing drugs, but a challenge is that these drugs also block critical signals required for Treg function. To address this roadblock, I will investigate whether Tregs can be modified to resist common immune-suppressive drugs. First, I will use genetic engineering technology called CRISPR-Cas9, which allows specific deletion of target genes in human cells, including in Tregs. I will use this technology to make Tregs that are resistant to a commonly used immune-suppressing drug. Second, I will investigate whether a synthetic microparticle can be used to deliver signals to activate Tregs which will most effectively suppress organ rejection. I will conduct this research using a mouse model of transplantation, which is already set up. My research will include experiments such as following the number and characteristics of the engineered Tregs used to treat mice, and determining their effects on the outcome of the transplant. Treg therapies are already in clinical testing in organ transplantation. This research is needed to design a next generation of Treg therapies that can effectively be used together with immune suppressing drugs in future clinical trials. Ultimately, the goal is to improve the long-term acceptance of organ transplants.