Project Leaders:   
Paul Keown, Bruce McManus, Robert McMaster

Involved Institutions:   
St Paul's Hospital - University of British Columbia; Vancouver Coastal Health Research Institute (VCHRI @ VGH) - University of British Columbia

Technology Applications:   
Personalized medicine, diagnostic markers

Research Funding Program:   
Applied Health

Transplantation remains the main therapy for patients with end-stage vital organ failure but long-term survival has improved only slightly in the last 20 years. The recipient’s immune system may react to the new organ, leading to organ rejection and dysfunction. In order to prevent organ rejection, powerful therapies are used to suppress a patient's immune system. While such therapies reduce the probability that the patient's own body will attack the transplanted organ, impairing the immune system may leave the patient susceptible to infections and malignancies, and may cause functional complications in precious transplanted organs.

A major difficulty in management of transplant recipients is the lack of prognostic assays capable of predicting graft rejection. Most current methods for detecting graft injury require highly invasive and risky procedures, such as tissue biopsies. This project will develop sensitive accurate biomarkers of the graft and the immune response by defining genomic and proteomic expression profiles that correspond to graft rejection.
This investigative team will use advanced genomic, proteomic, and bioinformatic tools to better understand variations in acute or chronic tissue rejection in heart, liver, and kidney transplant patients. The research will provide a predictive set of biomarkers for organ rejection that will guide the surveillance and management of immunosuppression plus enable physicians to adjust therapies to prevent graft injury or avoid toxicity. This personalized immunosuppressant therapy will not only alleviate patient discomfort but will reduce the enormous economic burden associated with the over-prescription of immunosuppressive drugs. In addition to the tools that will allow physicians to monitor organ rejection reliably, this research will generate a better understanding of transplant immunology and pathogenesis.

The research team will determine common genomic and/or proteomic expression profiles in allo-reactive T-lymphocytes, serum or urine that can be used as markers of immune status and graft rejection. To provide insight into the extent of immune tolerance, the differential expression of rejection and accommodation exhibited by kidney, heart, and liver transplants will be compared.

This project will then develop novel, minimally invasive, rapid tests for prognosis and diagnosis in transplantation management. The ability to monitor and predict rejection without invasive procedures will allow physicians and patients to react to organ rejection in a timely, painless, and cost-effective manner.