The CDTRP would like to congratulate Dr. Zhu-Xu Zhang (Associate Professor, University of Western Ontario) and Dr. Anthony Jevnikar (Scientist, Lawson Health Research Institute) on their recent success in the Fall 2019 CIHR project grant competition. Drs Zhang and Jevnikar were awarded $550,800 over 5 years to support their project; shown below.
TLR3 is an endogenous sensor of cell death and a potential target for induction of long-term heart transplant survival
When a graft is irreversibly damaged and cannot be treated by any other medical or surgical means, organ transplantation is the most beneficial and highly-pursued treatment option for saving the person’s life. Despite improved transplant rejection rates, premature graft failure in patients has become our greatest challenge, with 50% of all transplants failing over time. Consequently, searching for new strategies to limit the damage caused by unwanted immune responses and to prolong long-term graft survival has become the key objective in the field of transplantation research.
Post transplantation, inflammation is inevitable and is directly linked to diverse cell death programs and subsequent organ dysfunction and graft failure. Inflammation post transplantation induces different “forms” of cell death and subsequently organ failure. We have discovered that a unique form of cell death termed “necroptosis” differs from more typical cell death (apoptosis) in that it may lead to increased inflammation within the heart and kidney graft and contribute to long term injury. Furthermore, this inflammation is not affected by current anti-rejection drugs. Thus, controlling molecules within cells can convert heart cells from death-sensitive to death-resistant phenotype.
In this grant, we will study how the form of cell death regulate transplant inflammation and rejection. The development of novel therapeutic approaches to maintain long-term heart graft survival include: 1) explore affect of the form of cell death on immune responses and chronic transplant injury; 2) discovering the new role of cell death in heart graft injury and its impact on female and male heart grafts and; 3) using either gene manipulation or drugs to eliminate early heart graft damage. These studies will guide future clinical therapy of inflammation and may translate to truly new approaches to preventing transplanted heart graft injury in patients.
How the CDTRP has helped with our research program or supported our applications/progress/ work?
“The CDTRP has surely helped with our research. Regular CDTRP online meetings helped us to gain more advanced knowledge in transplant research. The support letter from the CDTRP played an important role in the success of our CIHR grant application. The reviewers commented that our project will be integrated in Theme 3 and 4 of the CDTRP and will have access to support for trainees and access to clinical expertise. With CIHR funded support, we are looking forward to enrolling trainees in our training platform and working with the CDTRP to disseminate the knowledge gained in this work in the future” – Dr. Zhang