Kidney transplantation remains the treatment of choice for patients with kidney failure. Unfortunately, the lifespan of transplanted kidneys has not changed over the years despite the advent of modern immunosupprerssive therapies. Significant barriers to long-term survival of kidney transplants are chronic immunologic rejection and long-term kidney toxicity from medications, both of which are limitations of current immunosuppressive therapies. The ability to reduce the incidence of acute and chronic rejection, and at the same time limit the use of toxic medications, is the ultimate goal of transplantation.
A major contributor to rejection and poor long-term outcome is ischemia reperfusion injury, an inevitable form of early tissue injury that occurs during organ harvesting and transplant surgery. New evidence suggests that “danger” signals released by injured or dying kidney epithelial cells (from the transplant) enhance the immunogenicity of the transplanted kidney by triggering a potent innate immune response.
The Gunaratnam Lab is devoted to understanding innate immune pathways in ischemia reperfusion injury. Dr. Gunaratnam’s team is studying the potential role of kidney injury molecule-1, a protein that is expressed by the kidney tubular epithelial cells soon after injury, in regulating the innate immune response. By uncovering the detailed mechanisms that enable kidney epithelial cells to control early inflammation following transplant surgery, they hope to identify specific therapeutic strategies to increase the lifespan of transplanted kidneys.
More recently, the lab has been collaborating with the laboratory of Dr. Alp Sener (see links), a surgeon-scientist at Western University, to investigate the molecular mechanism(s) of action of hydrogen sulphide that has been shown to protect against renal ischemia-reperfusion injury. Both laboratories are situated within a shared space within the Matthew Mailing Centre for Translational Transplant Studies and Western University and is supported by a generous infrastructure grant from the Canadian Foundation for Innovation.