Research Group
- Prof. Philip Halloran, Principal Investigator
Location
- University of Alberta, Edmonton, Canada
Title
- Mechanisms of Renal Allograft Rejection
Our aim is to identify the mechanisms of tissue injury and destruction in kidney transplant rejection. The mechanisms of graft rejection remain known and are important. Even though immunosuppressive drugs can now arrest rejection in many cases, these drugs have harmful effects. Rejection can be hard to recognize and treat, because we do not understand the mechanisms of destruction. The old methods of exploring mechanisms have been hampered because many mechanisms produce similar ultimate effects: destruction and failure of the graft. So failure alone is not a good way to look at mechanisms. To identify the important mechanisms for human rejection, our new approach is to focus on pathology. In other words, we study mechanisms in models that exactly mimic the processes seen in clinical rejection, particularly the process called tubulitis.
We have developed a mouse system in which the pathology is similar to that seen in rejecting human kidney transplants. We will study the mechanisms of tubulitis using mice that lack specific mechanisms. That way we can test which mechanism is needed for tubulitis to develop. We will study how the lymphocytes stick to the kidney tissue (the tubules), and whether they use a protein called CD103. We will explore how the glue that holds kidney units together – E cadherin – changes during rejection. Finally we will try to find the "fingerprint" of tubulitis by using gene "chip" methods.
If successful, the findings will have direct applications to human clinical transplantation. They will help us to diagnose rejection, to develop new drugs, and to find new ways of creating a favorable environment in the patient for the graft, to avoid rejection without drugs.
