Welcome to the latest issue of the Research Spotlight.
As Canada’s largest research hospital, UHN is a national and international source for discovery, education, and patient care. This newsletter highlights top research advancements from over 5000 members of TeamUHN—a diverse group of trainees, staff, and principal investigators who conduct research at UHN.
Stories in this month’s issue:
Read these stories and more online here. To read previous issues, see the newsletter archive.
Excessive bleeding is a common complication of cardiac surgery that can increase the risk of mortality. In a recent clinical trial, researchers at the Toronto General Hospital Research Institute (TGHRI) found that a drug called prothrombin complex concentrate (PCC, which goes by the brand name Octaplex®/Balfaxar®) is more effective at treating this complication than current treatments.
One important contributor to excessive bleeding after cardiac surgery is the depletion of enzymes that help blood clot. The standard treatment for this complication is the transfusion of frozen plasma (FP)—the liquid part of blood that contains clotting factors and is frozen for later use.
However, data on FP's effectiveness is limited, and it can cause life-threatening complications such as serious allergic reactions, transfusion-related acute lung injury, and transfusion-associated circulatory overload.
Recent preliminary data suggests that PCC, which is derived from large plasma pools and contains blood clotting factors and other proteins, may be a safer alternative to FP. A recent pilot study by a research team, led by Dr. Keyvan Karkouti, Senior Scientist at TGHRI, found that PCC may be more effective than FP in treating bleeding without increasing risk.
To confirm these results and determine PCC’s safety and efficacy in a larger, randomized trial, Dr. Karkouti’s team studied 420 adult cardiac surgery patients who required clotting factor replacement due to excessive bleeding after their procedure. They found that PCC was better than FP at stopping bleeding (77.9% versus 60.4% effectiveness). Serious adverse events were also less common (36.2% versus 47.3%), as was acute kidney injury (10.3% versus 18.8%).
“These findings indicate that PCC is a potential new treatment for managing bleeding in cardiac surgery. PCC benefits both patients and the health care system by reducing bleeding and the need for transfusions,” says Dr. Karkouti, co-lead of the study. "However, the clinical and financial impacts of this change need to be assessed in future studies.”
Dr. Keyvan Karkouti, Senior Scientist at the Toronto General Hospital Research Institute (TGHRI) and Professor in the Department of Anesthesiology and Pain Medicine at the University of Toronto (U of T), is the corresponding and co-first author of the study.
Dr. Jeannie L. Callum, Professor in the Department of Pathology and Molecular Medicine at Queen’s University and Associate Scientist at Sunnybrook Health Sciences Centre, is a co-first author of the study.
Authorship for this study also includes the FARES-II study group.
This work was supported by Octapharma AG, the Canadian Institutes of Health Research, the Department of Anesthesiology and Pain Medicine at the University of Toronto, and UHN Foundation.
The trial was conducted jointly by Octapharma AG (the sponsor), the Department of Anesthesia and Pain Management Clinical Trials Unit (ACTU) at UHN, and Ozmosis Research Inc.
Karkouti K, Callum JL, Bartoszko J, Tanaka KA, Knaub S, Brar S, Ghadimi K, Rochon A, Mullane D, Couture EJ, Lin Y, Harle C, Zeller M, Tran DTT, Solomon C, Rao V, Law M, Butt AL, Chen EP, Martins MR, Saha T, Shih AW, Vézina MC, Moussa F, Pereira Cezar Zamper R, Syed S, Buyukdere H, Werner S, Grewal D, Wong D, Vandyck KB, Tanzola R, Hughes B, Royer O, Wong S, Levy JH; FARES-II Study Group. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial. JAMA. 2025 Mar 29. doi: 10.1001/jama.2025.3501.
In a recent clinical trial, researchers from Princess Margaret Cancer Centre (PM) investigated the drug rucarparib in comparison to standard chemotherapy for treating patients with relapsed ovarian cancer caused by BRCA gene mutations.
Most patients with advanced high-grade ovarian cancer respond to initial treatment but eventually relapse. This recurrent disease is generally incurable. Rucaparib has demonstrated efficacy in patients with a specific type of recurrent ovarian cancer. It inhibits poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair.
To expand on previous evidence, including phase II clinical trials, Dr. Amit Oza’s group at PM led a randomized, controlled phase III trial, called ARIEL4. ARIEL4 compared rucaparib with the current standard-of-care chemotherapy in patients with relapsed ovarian cancer with BRCA mutations.
The trial involved 349 women from 12 countries who had previously undergone at least two chemotherapy treatments. They were randomly assigned to receive either rucaparib, taken as a daily pill, or chemotherapy. This cohort differed from previous studies because it included individuals with varying sensitivity to platinum-based chemotherapy, the standard first-line treatment for ovarian cancer.
The final report of this clinical trial examined overall survival, defined as the duration a patient lives following treatment. Overall survival was longer in patients assigned to chemotherapy (25.4 months) than those assigned to rucaparib (19.4 months). The research team suggested this could be attributed to one chemotherapy subgroup exhibiting greater resistance to treatment. In addition, no new or unexpected side effects were found in patients taking rucaparib.
However, the study did find that progression-free survival—the amount of time it takes for the disease to progress or get worse —was significantly longer with rucaparib than chemotherapy. These results were reported in a previous publication for the ARIEL4 study. Although the study was not designed to identify statistical differences between chemotherapy subgroups, this report found that patients in the rucaparib group had similar or longer progression-free survival versus patients in the chemotherapy group across all subgroups.
Researchers emphasize the need for further studies to optimize the use of PARP inhibitors, such as rucaparib, in combination with chemotherapy for advanced ovarian cancer treatment. Understanding the optimal treatment strategy could significantly impact patient outcomes.
The senior author of this study is Dr. Amit Oza, Senior Scientist at Princess Margaret Cancer Centre and Professor of Medicine at the University of Toronto.
This work was supported by Clovis Oncology and The Princess Margaret Cancer Foundation.
Dr. Amit Oza reports institutional research grants from AstraZeneca; has served on an advisory board (uncompensated) for GlaxoSmithKline; has served on advisory boards and steering committees (uncompensated) for Clovis Oncology and AstraZeneca; and as a principal investigator on investigator-initiated trials for Clovis Oncology, AstraZeneca, and GlaxoSmithKline.
For a full list of competing interests, see the manuscript.
Oza AM, Lisyanskaya A, Fedenko A, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Kristeleit R. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Feb;26(2):249-264. doi: 10.1016/S1470-2045(24)00674-0.
This past week, UHN hosted its inaugural Mission Excellence Awards, celebrating individuals and teams making outstanding contributions to help UHN realize its vision of A Healthier World. These awards combine the previous Local Impact Awards, Inventor of the Year, and Global Impact Awards, presenting them together in one program to elevate recognition and celebration.
During the ceremony, several members of the UHN research community were recognized for their hard work, commitment to excellence, and contribution to realizing UHN’s mission and vision.
UHN Global Impact Award
This award, which recognizes a current member or alumnus of TeamUHN, honours outstanding contributions to improving health and health care here and around the world. The UHN Global Impact Award has honoured giants in the field of medical research since its inception in 2004.
This year the award was given to Drs. Dafna Gladman, Emerita Scientist from Schroeder Arthritis Institute, and Daniel Cattran, Emeritus Scientist from the Toronto General Hospital Research Institute, to honour their outstanding contributions to health care, research, and education in rheumatology and kidney disease, respectively.
UHN President’s Patient Partner Award
As part of our strategic direction of Alignment for Impact, UHN bestows this award upon the UHN Patient Partners who play a vital and active role in co-creating care models, advancing person-centred care, and contributing to health system transformation.
The 2025 UHN President’s Patient Partner Award was given to UHN’s KITE Patient Engagement in Research (PiPER) Toolkit Co-Design Team to recognize the incredible impact that co-developing the Pride in Patient Engagement in Research toolkit has had on engaging patients, and their families and caregivers in research at UHN.
UHN Inventor of the Year Award
This award recognizes outstanding achievements that enable, and lead commercialization and partnerships related to UHN innovations and help create A Healthier World.
This year’s awardees were Drs. John Dick, Senior Scientist at the Princess Margaret Cancer Centre (PM), Jean Wang, Clinician Scientist at PM, and Jayne Danska, Senior Scientist at the Hospital for Sick Children. The UHN Inventor of the Year Award recognizes their innovative work in cancer immunotherapy in identifying a novel way that cancer cells evade discovery.
Congratulations to all the awardees recognized on this momentous night. Your continued dedication to your work and to bettering health and health care for the UHN community and beyond is central to making UHN what it is.
Read the story with a full list of awards and awardees originally posted by UHN here.
Congratulations to Drs. Jean Wang and John Dick of the Princess Margaret Cancer Centre, along with Dr. Jayne Danska of SickKids Research Institute, on winning UHN’s 2024 Inventor of the Year Award.
Drs. Wang, Dick, and Danska are recognized for their innovative work in cancer immunotherapy, identifying a novel mechanism by which cancer cells evade destruction. A discovery made decades ago at UHN and The Hospital for Sick Children led to a multibillion-dollar pharmaceutical deal, shaping new cancer treatments.
At the heart of their discovery lies the immune system’s ability to detect and destroy cancer cells. Cancer cells use a deceptive signal, nicknamed the ‘Don’t Eat Me’ signal, to evade immune attacks. The researchers developed a novel molecule, TTI-621, that targets a key molecule on cancer cells, CD47, blocking the transmission of the 'Dont Eat Me' signal and allowing the immune system to recognize and eliminate cancer cells more effectively.
This discovery laid the foundation for UHN start up, Trillium Therapeutics, launched in 2004 to commercialize this technology. In 2022, Pfizer Inc. acquired Trillium Therapeutics in a US$2.22 billion deal to further develop TTI-621, renaming the drug Maplirpacept. As of February 2025, Maplirpacept remains in global Phase II clinical trials for the treatment of a variety of blood cancers.
The award was presented to Drs. Wang, Dick, and Danska at UHN’s inaugural Mission Excellence Awards, which celebrate individuals and teams making outstanding contributions toward UHN’s vision of A Healthier World. See the full list of Mission Excellence Awards winners here and learn more about the discovery and commercialization of TTI-621 here.
The Inventor of the Year award is sponsored by Commercialization at UHN and recognizes an individual or team whose invention has made a substantial commercialization impact, contributing to UHN’s mission of ‘A Healthier World’. Read the full announcement here.
For more than four decades, Katie Roposa has been a dedicated member of the UHN community, contributing to the culture of excellence, collaboration, innovation, and patient care. Now, as she prepares to retire on March 31, 2025, we take a moment to celebrate the profound impact she has had on our institution, our people, and the countless patients whose lives have been touched by her work.
Katie’s journey with UHN began in 1984 as a staff nurse in General Medicine. From the bedside to leadership in clinical research, she embraced every role with unwavering dedication, spending a decade in critical care and transplant coordination before transitioning to clinical research. As a key driver in research quality and integrity, she played a pivotal role in establishing the Clinical Studies Resource Centre and later in developing the Research Quality Integration department. Her expertise in clinical research regulation and risk management has been instrumental in guiding UHN’s operational excellence.
Beyond her professional impact, Katie’s ties to UHN run deep. It was here that she met her husband, a fellow long-standing UHN team member, and together their family has amassed over 100 years of service to the organization. Their story is a testament to the strong sense of community and belonging that UHN fosters. (Read more about Katie’s remarkable journey: Couple celebrates more than 25 years at UHN.)
Katie’s leadership, wisdom, and compassion have left an indelible mark on her colleagues and the broader scientific community. Her mentorship has nurtured countless professionals, and her commitment to excellence has set a standard that will continue to inspire. Those who have worked with Katie describe her as a dedicated professional with an unparalleled ability to bring people together, solve complex challenges, and advocate for the highest standards in research and patient care.
Reflecting on her time at UHN, Katie shared, “UHN has evolved over the years, but its heart remains the same—it’s the people who make it extraordinary. I’ve had the privilege of growing through nine different roles here, and at every step, it’s the connections that have mattered most. When we bring our whole selves to work, we shape UHN, just as UHN shapes us. It’s through these relationships that we find purpose, make a difference, and grow together.”
As we celebrate Katie’s incredible legacy, we also recognize the friendships, lessons, and impact she leaves behind. Though her presence in the hallways of UHN will be missed, her influence will endure through the many people she has mentored and the programs she has built.
Katie's career has been nothing short of remarkable. She has shaped UHN in ways that will be felt for years to come, and her contributions are deeply appreciated. As she embarks on this next chapter, we celebrate her incredible contributions and wish her a retirement filled with joy, adventure, and well-earned relaxation.
Researchers at Toronto General Hospital Research Institute (TGHRI) and the Ajmera Transplant Centre have identified an important early warning sign that could help doctors predict the success of liver transplants.
UHN’s Multi-Organ Transplant Program, which includes its Liver Program, at Ajmera Transplant Centre, is the largest transplant program in Canada, with world-renowned researchers studying clinical transplantation and modelling human disease.
Liver transplants are considered a first-line treatment for end-stage liver disease and the only curative option for many patients with hepatocellular carcinoma—the most common type of liver cancer. However, the need for donor tissue is greater than the supply.
To increase the availability of donor tissue, more types of grafts—tissue taken from one part of the body and used to replace diseased or injured tissue—are being used. These grafts, while broadening the donor pool, can come from older donors or organs in poorer health and therefore have an increased likelihood of causing graft dysfunction.
Thus, there is a need for an early and accurate way to assess grafts for dysfunction post-transplant. Blood clotting proteins have previously been studied as a marker of liver function, but research in this area has been limited. One of these proteins, known as Factor V, is solely produced in the liver and a previous, retrospective study has linked its levels with graft loss.
To further validate the use of Factor V as a marker of graft function and expand the current understanding of its role in liver function, the team followed 129 liver transplant patients, measuring Factor V levels at various points after the procedure. They then analyzed graft and patient survival at three, six, and twelve months.
The researchers identified an optimal Factor V level that can predict graft and patient outcomes. They found that patients with Factor V levels below 0.46 U/mL on the first day after surgery had lower graft and patient survival rates compared to those with higher levels. Specifically, at one year, 98.8% of patients with higher Factor V levels experienced graft survival, compared to just 87.7% of those with lower levels. Patient survival also dropped from 95% to 82.9% in the low-Factor V group.
These results suggest that Factor V could serve as a valuable early indicator, helping doctors identify patients at risk and adjust treatments accordingly. More studies are needed to confirm these findings and determine how this biomarker could improve transplant outcomes.
First author of this study is Annabel K. Gravely, research student with the liver transplant oncology research group that Dr. Gonzalo Sapisochin leads at UHN.
Senior author of this study is Dr. Gonzalo Sapisochin, Clinician Investigator at Toronto General Hospital Research Institute (TGHRI), Staff Surgeon at Toronto General Hospital, and Associate Professor of Surgery at the University of Toronto.
This work was supported by the Natural Sciences and Engineering Research Council of Canada, and UHN Foundation.
Gravely AK, Claasen MPAW, Ivanics T, Winter E, Peralta P, Selzner M, Sapisochin G. Factor V Serves as an Early Biomarker for Graft Loss After Liver Transplant: A Prospective Evaluation. Clin Transplant. 2025 Feb;39(2):e70086. doi: 10.1111/ctr.70086.
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
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