CIHR funding boost helps answer challenging questions that could save lives
By Cam Buchan
An antibiotic-resistant bacteria that has jumped from the hospital to the community is gaining ground, but to this point, an accurate picture of just how much is unknown.
And a promising surgical technique that offers hope for improving the quantity and quality of organs recovered for donation is caught up in a divisive ethical battle that prevents its uptake.
And in both instances, lives are literally at stake.
These are just two of the groundbreaking research projects underway by Schulich Medicine & Dentistry researchers who – combined – received more than $7 million in funding from the Canadian Institutes of Health Research (CIHR) through its latest project grants competition.
The results from the Spring 2024 competition saw an 80-per-cent increase in the number of submissions compared to Spring 2023, and the second consecutive competition with a significant increase in applications, said Robert Bartha, PhD, Vice Dean of Research & Innovation.
“This is a major accomplishment for our School that will pay significant dividends in successful labs and energize our research enterprise. It’s a testament to the hard work of so many of our faculty and staff,” Bartha said. “The trajectory for applications is certainly going up which is exciting and demonstrates the re-engagement and vision of our community. We are working on additional mentorship opportunities to help investigators increase the quality of their applications.”
Gaining a foothold in the community
No one really knows how big the problem is.
But you could run into it at the gym, on public transportation or even just pushing an elevator button.
Methicillin-resistant Staphylococcus aureus (MRSA) – known for causing severe infections in hospitals – has now spread widely in communities, posing significant health risks due to its ability to easily acquire genes from other bacteria that make it harder to treat with antibiotics.
And during the pandemic, industrial cleaning agents that were highly effective at killing viruses, including the virus that causes COVID-19, may have made these bacteria even more resilient.
With the help of CIHR project funding, Jennifer Guthrie, PhD, assistant professor in the Department of Microbiology and Immunology, is developing a national platform to better understand just how big the problem has become and what lessons can be learned in facing future pandemics. The project is called MRSA Genomics: Advancing Knowledge for Effective Intervention.
“In downtown Toronto during the pandemic in our building alone they were wiping down elevator buttons, handles, stair railings, and everything else with all kinds of cleaning agents,” explained Guthrie. “Did these bugs, already multi-drug resistant, become more dangerous? And should we be concerned?”
Initial data from her team indicates the answer to both questions is “Yes.”
The challenge in trying to identify MRSA’s foothold in the community is the lack of data, leaving Guthrie to start basically from scratch.
Beginning in Ontario, Guthrie and team will gather relevant hospital data through the Canadian Nosocomial Infection Surveillance Program (CNISP) along with information from a wastewater surveillance program provided by Larry Goodridge at the University of Guelph. To round out the view, Dr. Scott Weese, a veterinarian and researcher at the Ontario Veterinary College, will provide insight into whether MRSA is showing up in pets that can act as a reservoir for these drug resistant bugs.
“We hope to develop a routine surveillance program to keep an eye on what’s happening in the community,” said Guthrie, who brings 17 years of public health experience to her work. “And if there was an impact from the pandemic, what we can learn from it on the public health side.”
Guthrie will work with researchers from across Canada, including Jared Simpson, PhD, Dr. Allison McGeer, Dr. Kevin Katz, Dr. George Golding, Idowu Olawoye, PhD, Finlay Maguire, PhD, and Madelyn Law, PhD.
A challenging pathway
Dr. Charles Weijer, MD, PhD
Professor
Departments of Medicine and Philosophy
There are approximately 1,400 people waiting for a life-saving organ transplant in Ontario, and every three days someone will die while waiting, according to data from Ontario Health Trillium Gift of Life.
And Dr. Charles Weijer, MD, PhD, is in the middle of the fray.
“These are preventable deaths,” said Weijer, a professor in the Departments of Medicine and Philosophy, and an internationally recognized expert in research ethics. “If we had more organs, those people probably would have survived.”
One particular pathway to organ donation, called circulatory determination of death (CDD) is the process of declaring a person dead based on the permanent cessation of blood circulation and heart function. Unfortunately, organs used for donation will be damaged due to loss of oxygen and nutrients.
The technique in question, called Normothermic Regional Perfusion (NRP), can improve the quality and quantity of organs recovered for donation once a patient has been declared dead by circulatory determination of death (CCD).
While the procedure is widely used in Europe and increasingly in the United States, it’s a hotly contested ethical issue in many areas of the world, including Canada.
Weijer and his research team have recently completed a review of the ethical issues surrounding NRP, and the results have been published in Transplantation.
Now new project funding from the Canadian Institutes of Health Research (CIHR) will enable Weijer and an extensive group of colleagues, including researchers from several Western faculties, to build a national platform for implementation of the NRP procedure in a way that preserves trust between stakeholders.
“There are several really difficult ethical challenges raised by NRP,” said Weijer. “One is that we’re on this organ donation pathway where individuals are declared dead based on permanent cessation of circulatory function, then we’re planning to hook them up to a machine that is going to restart their circulation. Haven’t we undermined the very basis of their death determination?”
Another concern is that, if oxygenated blood perfuses the brain, it could potentially lead to the reanimation of brain activity or function, “and that’s not good. This could in theory lead to restoration of some degree of consciousness and the ability to experience pain and suffering and that would obviously be a major harm to the donor.”
While NRP offers the promise of improving the numbers of organs retrieved and improving outcomes, Weijer said its potential can’t be achieved if trust in the organ donation system is undermined.
“This project is about building a national platform to ensure a responsible adoption of NRP to help donors achieve their goals of helping others and, crucially, preserve trust in organ donation in Canada.”
Weijer is working with co-principal applicants Lorelei Lingard, PhD, and Dr. Marat Slessarev, PhD, from the Department of Medicine and Dr. Matthew Weiss from the University of Laval and an extensive team that includes Western faculty from Schulich Medicine & Dentistry, Education, Health Sciences and Arts & Humanities, plus other universities, donor families and organ recipients and five provincial organ donation organizations.
Congratulations to the other CIHR Project Grant recipients:
Frederick Dick, PhD
Understanding pattern recognition receptor signaling in homeostasis and cancer.
Lauren Flynn, PhD (Gregory Dekaban, PhD, Paula Foster, PhD, Mamadou Diop, PhD, David Hess, PhD)
Delivery of human monocytes and adipose‐derived stromal cells within decellularized adipose tissue hydrogels for peripheral vascular regeneration.
Bryan Heit, PhD (Steven Kerfoot, PhD)
Guardians of Immunity: Investigating the Reciprocal Influence of Apoptotic Cells and Pathogens on MHC II Regulation and Vesicular Trafficking.
Dr. Kun Ping Lu (Dr. Douglas Fraser, Dr. Xiao Zhen Zhou)
Identification of Novel Disease Drivers, Therapeutic Targets, and Biomarkers of Sepsis.
Marco Prado, PhD
Role of the co‐chaperone STIP1 in alpha‐synuclein spreading, aggregation and toxicity.
Sisira Sarma, PhD (Shehzad Ali, PhD, Steven Habbous, PhD, Dr. Liisa Jaakkimainen, Dr. Kristin Clemens, Kelly Anderson, PhD, Rose Anne Devlin, PhD, Dr. Saverio Stranges, PhD, Guangyong Zou, PhD)
Interprofessional Primary Care Teams and Quintuple‐aim Outcomes: Longitudinal Investigation.
Congratulations to the CIHR Priority Announcement recipients:
Jibran Khokhar, PhD (Marie‐Ève Tremblay, PhD, Haley Vecchiarelli, PhD)
Sex Differences in Cannabis Use as a Risk Factor for Schizophrenia: A Role for Microglia?
Maria Mathews, PhD (Dr. Alexander Summers, Dr. Jamie Wickett, Lindsay Hedden, PhD, Emily Marshall, PhD, Gillian Young, Dr. Daniel Grushka, Dr. Sandra Mackenzie, Ashley Bilodeau, Dr. Stephen Wetmore, Dr. Andrea Gillan, Dr. Tom Freeman, Dr. Eric Wong, Arianna DiSchiavi, Joanne Kearon, Paul Gill, Erin Kennedy, PhD, Julia Lukewich, PhD)
3PC‐I: Pandemic Planning for Primary Care ‐ Implementing a plan in Southwestern Ontario.
Krishna Singh, PhD (David Hess, PhD, Robert Gros, PhD, Alison Allan, PhD)
Novel Mechanisms in Doxorubicin‐induced Cardiomyopathy.
