Congratulations to the CNTRP Researchers who received CIHR Project Grants in the Fall 2016 competiti
The results for the 2016 Fall CIHR Project Grant competition were recently announced and we congratulate the following CNTRP members for their success in this highly competitive competition.
The following investigators included CNTRP support in their application and will be integrated into the structure of the CNTRP (see abstracts below):
CIHR PROJECT GRANT RECIPIENTS (CNTRP supported)
Dr. Megan Levings - UBC - Tailoring Regulatory T cells for Transplantation Tolerance (Project 4)
Dr. Lakshman Gunaratnam - University of Western Ontario - The Role of Kidney Injury Molecule-1 in Renal Transplantation (Project 3)
Dr. Lori West - UofA - Crowd-sourcing multiple tolerizing cell types to induce robust transplant tolerance in mice: towards a clinically relevant approach (CIHR Bridge Grant) (Project 4)
For Dr. Levings' application, one reviewer commented on the strength of the CNTRP in supporting the research:
"Strength: Support letter from the CNTRP with opportunity to leverage the Clinical Trials platform and CellCAN, the immune monitoring platform built by the PI, and the research support available through their networks."
Congratulations to these three researchers and we look forward to working with you to support your research and integrate these new projects into the CNTRP.
CIHR Successes for our CNTRP Investigators, Associates and Collaborators
We would also like to congratulate and acknowledge our CNTRP investigators, associates and collaborators on receiving CIHR Project and Bridge Grants for research outside of the CNTRP:
Dr. Jennifer Reed - Ottawa Heart Institute - Exercise Training in Patients with Persistent or Permanent Atrial Fibrillation
Dr. Monica Taljaard - Ottawa Hospital Research Institute - Developing a framework for the ethical design and conduct of pragmatic trials to improve the quality and value of health care systems and practices
Dr. Kevin Burns - Ottawa Hospital Research Institute - Endothelial Progenitor Cell Exosomes and MicroRNA Transfer as Therapy for Acute Kidney Injury (CIHR Bridge Grant)
Dr. Bruce McManus - UBC - A novel multi-marker blood test for management of acute cardiac allograft rejection (CIHR Bridge Grant)
Dr. Susan Samuel - University of Calgary - Evaluating Innovations in Transition to Adult Care: Transition Navigator Trial (CIHR Bridge Grant)
Dr. Jean-Claude Tardif - Montreal Heart Institute - Colchicine Cardiovascular Outcomes Trial (CIHR Bridge Grant)
Dr. Emmanuelle Brochiero - CHUM - K+ channels as key targets to favor alveolar epithelial integrity and function during the resolution of acute respiratory distress syndrome (CIHR Bridge Grant)
For CNTRP Investigators interested in applying for the next 2017 CIHR Foundation and Project Scheme Grant application (due in the fall 2017), we encourage you to work with the CNTRP Project, Cores and the New Initiatives Committee to discuss how we can help support your research program and get a support letter from the CNTRP for your application. . Please contact David Hartell soon for more information and click here to see what support the CNTRP can offer.
Tailoring Regulatory T cells for Transplantation Tolerance
Dr. Megan Levings - UBC
Transplantation is the best treatment for end-stage organ failure. In the past ten years, more than 20,000 Canadians have had their lives improved or saved by donated organs. Organ transplantation is only possible because immunosuppressive drugs prevent rejection, but these drugs also bring increased risks of infection, cancer, and many other side effects. Our goal is to find ways to educate the patient's immune system to accept a transplanted organ, without high doses of immunosuppressive medication. Our strategy is to harness the natural properties of a type of white blood cell called a T regulatory cell (Treg). Tregs modulate immune responses -not too much, not too little - and if used therapeutically, they could control immune responses to transplanted tissues and organs. Here, we aim to discover ways to engineer Tregs so that they are maximally effective. First we will modify Tregs so they can be specifically activated by the foreign tissue of the transplant. We will test the therapeutic effect of these genetically-modified Tregs in animal models of transplantation (specifically, transplant of pancreas cells or lung) and explore the possible safety-related limitations of the approach. We will also ask if genetically-modified Tregs have the potential to induce long-lasting effects, meaning that "booster" injections of more Tregs may not be needed to control immune responses. Finally, we will create new ways to manufacture Tregs using conditions to tailor their function depending on the clinical context. These tailored Tregs will be evaluated in animal models to test their effect. Data generated in this project will help in the design and testing of Tregs as a cell therapy in transplantation. By creating new ways to minimize the reliance on immunosuppressive drugs, our research has the potential to significantly increase the long-term success of transplantation.
The Role of Kidney Injury Molecule-1 in Renal Transplantation
Dr. Lakshman Gunaratnam - University of Western Ontario
Kidney transplantation is the ideal treatment for patients with end-stage kidney disease. Despite better drugs to suppress the immune system, however, the long-term survival of the transplants remains suboptimal. Damage of the kidney due to the lack of blood flow during organ procurement and cold storage before transplantation (ischemia-reperfusion injury, or IRI) is believed to be a major contributor to the limited lifespan of transplants. The tissue injury is further compounded by rejection episodes in the transplanted kidney. There is also growing evidence to suggest that IRI may interact with immune factors worsening graft injury. Kidney Injury Molecule-1 (KIM-1) is a protein produced by native and donor kidneys following injury. Using mice genetically engineered to be deficient in KIM-1, we previously showed that KIM-1 protects the native kidneys of mice from tissue damage and kidney dysfunction following IRI. Paradoxically, however, KIM-1 can also promote chronic kidney disease and scarring. Whether KIM-1 protects or is harmful in transplanted kidneys is unknown. In this project, we will use a mouse model of transplantation to help determine if KIM-1 in the transplanted kidney can protect it from tissue damage from IRI as well as from acute rejection, or whether KIM-1 leads to long-term scarring and premature graft loss. We will also test the therapeutic potential of a new molecule called AIM, which we have shown can protect native kidneys from the damaging effects of IRI via a KIM-1 dependent pathway, in improving the lifespan of transplanted organs. The findings from our proposed studies will advance our understanding of why transplanted kidneys fail prematurely, and help us to develop new potential treatments to prolong their lifespan.
Crowd-sourcing multiple tolerizing cell types to induce robust transplant tolerance in mice: towards a clinically relevant approach (CIHR Bridge Grant)
Dr. Lori West - UofA
Infants with severe heart disease often require transplants for survival. Without intervention, organ transplants are rejected by the recipient's immune system in a process that is complex and involves many cell types. To prevent rejection, transplant patients take powerful immunosuppressive drugs over their lifetime, which can lead to complications such as infections and cancer. Additionally, these drugs do not always successfully prevent rejection. We are searching for ways to "educate" the patient's immune system so that it can permanently tolerate the transplant without the need for immunosuppressive drugs. In the laboratory we study neonatal tolerance to heart transplants in mice, a powerful tool to ask questions that would not be feasible in human infants. In this research project we will deplete different cell types that are involved in rejection or that cause complications leaving behind the cells that induce tolerance. We will explore the earliest events that occur following depletion using special microscopes and fluorescent dyes. We will track the remaining cells and analyse their ability to induce and maintain tolerance. If successful such treatment will allow patients to accept their transplants with less need for immunosuppressive drugs. The technology would also be applicable to other types of transplants such as kidney.