PROJECTS & CORE PLATFORMS
The CNTRP encompasses six focused and synergistic projects and three comprehensive supporting cores.
Together, these teams are national in scope and address the CNTRP research goals. Each project, with support from the cores, addresses important and novel questions in one or more of the three clinical domains of SOT, HCT and donation.
Ex vivo organ transplant protection and repair
Project 1 is a multi-site study to investigate ex vivo repair and perfusion modalities across major transplant organs. This project is co-led by Dr. James Shapiro, a senior surgeon-scientist at the University of Alberta who is noted for the establishment of a globally transformative protocol for clinical islet transplantation, Dr. Markus Selzner, senior surgeon-scientist at the University of Toronto, and Dr. Darren Freed, cardiac surgeon at the University of Alberta. Project 1 investigates pre-clinical models and early clinical pilot studies of ex vivo perfusion of heart (Freed, Edmonton), kidney (Luke, London & Selzner, Toronto), liver (Selzner, Toronto & Shapiro, Edmonton), lung (Nagendran, Edmonton) and pancreas (Paraskevas, Montreal & Shapiro, Edmonton), taking advantage of commonalities across the organs while also considering the physiologic differences that require organ-specific approaches for optimal effect.
Increasing solid organ and hematopoietic cell donation
Project 2 defines and tests novel and ethically-acceptable modalities for expanding the donor pool in Canada. Project 2 is led by Dr. Sonny Dhanani, Chief, Critical Care at the Children's Hospital of Eastern Ontario, and Dr. Greg Knoll, medical director of kidney transplantation at the University of Ottawa. Project 2 is also co-led by Ms. Linda Wright, a recently retired senior medical bioethicist formerly at the University of Toronto, and Dr. Sam Shemie, a pediatric intensivist at McGill University and Canadian Blood Service. The national team of clinical scientists, bioethics and legal specialists working together in Project 2 define national strategies for recruitment of organ and hematopoietic cell donors to:
expand novel types of living kidney donation,
increase donation after cardiac death and donation after neurological death in Canada,
explore outcomes and ethical frameworks of ‘extended criteria’ donor organs, and
explore the issue of family override and substitute decision making in deceased donation
Understanding, predicting and preventing early graft rejection and GVHD
Project 3 develops early markers of rejection and GVHD by defining cell death and inflammation signatures through innovative and cost-effective proteomic approaches. Project 3 is led by Dr. Marie-Josée Hébert, senior nephrology clinician-scientist and vice-rector of research, discovery, creation and innovation at Université de Montréal, and co-led by Drs. Claude Perreault, Canada Research Chair in Immunobiology at Université de Montréal, and Dan Muruve, Canada Research Chair in Inflammation and Kidney Disease at the University of Calgary. Together, they have assembled a team of proteomics, cell death and inflammation specialists to work together to define cell death and inflammation signatures through innovative and cost-effective proteomic approaches. These signatures are tested as novel biologic markers of allograft dysfunction and predictors of rejection/GVHD.
Strategies for immunomodulation and transplant tolerance
Modulation of allo-reactivity and ultimate establishment of transplantation tolerance will improve survival of transplant recipients by minimizing prolonged requirements for immunosuppressive medications with potential adverse side-effects. Project 4 combines complementary SOT and HCT expertise to translate strategies to induce tolerance to the clinical setting. Project 4 tests several novel modes of immunomodulation in human transplant recipients, including phase I/II trials using extracorporeal photopheresis (ECP) to treat acute renal graft rejection and chronic GVHD and to promote immune regulation and a phase I clinical trial combining hematopoietic stem cell and kidney transplantation. Project 4 is jointly led by Dr. Megan Levings, transplant immunologist at UBC, and Dr. Denis-Claude Roy, a hematology clinician-scientist at Université de Montréal, and co-led by Dr. Kirk Schultz, senior pediatric hematologist at UBC, and Dr. Lori West.
Predicting and controlling
viral complications of transplantation
Viral infections are common after transplant and are important contributors to post-transplant morbidity, mortality and graft loss. Project 5 focuses on viral complications from across the transplantation spectrum with studies that span several critical aspects of virology and encompass themes important to donation, SOT and HCT. Project 5 is led by Dr. Atul Humar, Director of the MultiOrgan Transplant Program at the University Health Network in Toronto, and co-led by Dr. Lee Anne Tibbles, nephrology clinician-scientist at the University of Calgary and Director of ALTRA Transplant Program (Southern Alberta), and Dr. Jean-Sébastien Delisle, haematologist and immunology-oncology researcher at Hôpital Maisonneuve-Rosemont. Project 5 studies high infectious risk donors, examines anti-viral immunity in the tolerance setting integrates and looks at a nested cohort study on psychosocial factors related to receiving transplants from high infectious risk donors.
Addressing pediatric issues in transplantation
Age-specific challenges add to the complexity of providing health care in pediatric and young adult transplant recipients. Project 6 is the first comprehensive, multi-organ transplant study to identify age-related biologic and health care systems determinants of variability in immunosuppression control in children and youth. Results will inform personalized age-appropriate strategies to improve immunosuppression control and reduce the unacceptably high rates of graft failure, GVHD and viral complications in this vulnerable population. The Project 6 team is led by Dr. Seema Mital, a clinician-scientist at the Hospital for Sick, and co-led by Dr. Upton Allen, an expert at the Hospital for Sick Children in pediatric infectious diseases in immunocompromised hosts, and Dr. Beth Foster, pediatric transplant nephrologist at Montreal Children’s Hospital, who leads an NIH-funded multi-centre trial to improve medication adherence in adolescent kidney transplant recipients.
Ethical, economic, legal and social (EELS) platform
Core 1 provides EELS support to all project teams, and investigates the relevance of existing legislation and ethical norms to developing and implementing new donation incentives and procurement initiatives. Core 1 is led by Professor Tim Caulfield, Canada Research Chair in Health Law & Policy at the University of Alberta, and Co-led by Dr. Scott Klarenbach, a physician and health economist at the University of Alberta, and Professor Jennifer Chandler, associate professor in the Faculty of Law at the University of Ottawa. In addition to providing EELS support to the entire research team, Core 1 investigates the relevance of existing legal frameworks and ethical norms, public perceptions/representations in relation to several issues central to public support or fears about donation, and the development and implementation of novel incentives and procurement initiatives.
Research infrastructure and registries support platform
Core 2 provides critical infrastructure and operational support for all CNTRP projects and teams, including the establishment of the CNTRP Registry. Core 2 uses and strengthens existing registries, health care databases and biorepositories for effective implementation of national studies in transplantation. Dr. Kirk Schultz, senior hematologist-scientist at UBC with vast experience in clinical trials management, is Core 2 team lead and Peter Subrt is the Core 2 manager. The Core 2 team has nationwide multidisciplinary representation from highly experienced investigators in all three clinical domains (donation, HCT, SOT), and is sub-divided into 3 platforms:
Registries (lead Dr. Krisjtan Paulson, co-leads Drs. Peter Nickerson, John Gill, Joe Kim, Susan Samuel)
Interventional Trials (lead: Dr. Donna Wall, co-leads Drs. Jean-Claude Tardif, Greg Knoll and John Gill)
Biorepositories (lead: Dr. Kirk Schultz, co-leads Drs. Bruce Ritchie and Peter Subrt)
Improving outcomes for transplant recipients
The newest project in the CNTRP is focused on improving long-term outcomes and quality of life in solid organ and stem cell transplant recipients. Project 7 is led by Dr. Sunita Mathur, a physiotherapist and Assistant Professor in the Dept of Physical Therapy, and co-led by Dr. Maureen Meade, a Professor in the Department of Medicine at McMaster University, and Sandra Holdsworth, a liver transplant recipient who is co-leading Project 7. This new project assembled 18 active CNTRP Investigators and 19 additional Associate members and collaborators that are leading studies organized around the following aims:
Evaluation of co-morbidities, disability and quality of life in transplant candidates and recipients
Effectiveness of interventions in donors, candidates and recipients to mitigate co-morbidities and improve long-term outcomes and quality of life after transplantation
Improving long-term organ function through innovations in assessments and novel interventions
To increase knowledge uptake of Project 7 research findings by key stakeholders in transplantation (Knowledge Translation/Knowledge to Action cycle)
Project 7 is also the home of the CAN-Restore Program - Canadian Network for Rehabilitation and Exercise for Solid Organ Transplant Optimal Recovery. Visit their webiste to learn more about this research program.
Training and career development platform
The integrative nature of the CNTRP provides the opportunity to offer a unique training environment inclusive of both formal academic trainees and CNTRP participants brought together through program collaborations. The Training and Career Development Platform is led by Dr. Lee Anne Tibbles, from the University of Calgary representing SOT community, and co-led by Dr. Silvy Lachance, from the Université de Montréal representing the HCT community, and Dr. Sonny Dhanani, from the Children’s Hospital of Eastern Ontario representing the donation community. The Academic Training program fosters the integrated training of all graduate students, clinical and surgical fellows and postdoctoral scholars involved in the research projects and cores. The Broad-based Training program supports the comprehensive training of all CNTRP participants, including allied health and technical personnel.
The CNTRP supports the integration of patients, families and caregivers as research partners as part of our CNTRP Patient Partnership Platform (Core 4). The Core 4 team is co-led by Marie-Chantal Fortin (CRCHUM) and Sylvain Bédard (heart transplant recipient). The overall objectives of Core 4 are to:
give the patient a voice and be a catalyst for cultural transformation;
align CNTRP priorities and activities to ensure that the CNTRP remains relevant to the needs of patients;
contribute proactively to the design and implementation of the patient‑research partnership strategy;
play an active and positive role as knowledge transfer channels;
advise the CNTRP Executive Committee on any changes to strategy, policies and/or programs designed to improve the network’s patient partnership.