Advancements in lung and kidney transplantation are helping overcome one of the greatest challenges in organ donation: the shortage of viable donor organs.
Two new studies from UHN’s Ajmera Transplant Centre showcase innovative techniques that aim to expand the donor pool and improve access to life-saving transplants. These findings mark major steps forward in transplant medicine, offering hope to patients awaiting critical procedures.
A study led by Dr. Shaf Keshavjee, Senior Scientist and Chief of Innovation at UHN, evaluated the impact of ex vivo lung perfusion (EVLP) in the largest single-center study of EVLP outcomes to date. EVLP is a technique developed by Dr. Keshavjee and colleagues at UHN that enables donor lungs to be assessed and treated outside the body before transplant.
Having recently marked the 1,000th procedure of EVLP, the team conducted a retrospective study of the first 1,000 consecutive EVLP procedures performed at Toronto General Hospital between September 2008 and March 2024. They analyzed donor and recipient demographics, procedural characteristics, transplant rates, and post-transplant outcomes.
Of the 1,000 ex vivo lung perfusion procedures, approximately 65% of lungs were accepted for transplant. EVLP volume grew over time and contributed to an overall increase in transplantations, including the use of moderate- and high-risk donor lungs. Post-transplant outcomes, including intensive care unit duration and overall survival, did not differ significantly between EVLP and non-EVLP lungs.
Overall, these results show that EVLP is a safe and scalable approach that has expanded the donor pool, supported program growth, and set the stage for further innovation in lung transplantation
In another study focused on kidney transplantation and done in collaboration with SickKids Research Institute, researchers explored a novel method to extend the preservation time of donor kidneys—another promising approach to increasing organ availability. This study, co-led by Drs. Markus Selzner, Lisa Robinson, and Francisco Calderon Novoa, describes a new approach that could extend the viability of donor kidneys before transplant.
A shortage of donor organs continues to limit the number of kidney transplants performed worldwide. Typically, donor kidneys are cooled to 4°C prior to transplant and can be kept cold for up to 30 hours before the organ needs to be warmed and blood supply restored. Cooling a donor kidney below zero degrees Celsius without freezing (subzero preservation) could potentially expand organ sharing and even lead to organ banking.
In this study, the team tested a subzero preservation technique (subzero storage without freezing), designed to keep kidneys colder for longer without the damaging effects of freeze-thawing and ice crystal formation. Using research models, they compared kidneys stored for up to 48 hours using the subzero method against those kept in standard cold storage.
Results showed that kidney function and tissue health were comparable across all groups, and there were no signs of freeze-related injury. These findings provide evidence, for the first time in transplantation models, that subzero storage could be a safe and feasible way to extend organ preservation time. Future studies are needed to refine protocols further for improved outcomes.
Together, these studies show how technologies like EVLP and subzero kidney preservation can safely expand donor organ availability and improve access to life-saving transplants.
The Journal of Thoracic and Cardiovascular Surgery manuscript
Dr. Shaf Keshavjee is the first and corresponding author of the study. He is a Senior Scientist and Chief of Innovation at UHN. He is also a Professor of Thoracic Surgery and Biomedical Engineering, and Vice Chair for Innovation in the Department of Surgery the University of Toronto.
Dr. Shaf Keshavjee and several other co-authors are shareholders in Traferox Technologies Inc. Dr. Keshavjee serves as Chief Medical Officer and Chief Scientific Officer of the company. He and other co-authors also receive consulting fees from Lung Bioengineering and are listed as inventors on patents relevant to this work.
For a full account of competing interests, see the manuscript.
American Journal of Transplantation manuscript
Dr. Francisco Calderon Novoa is the first and corresponding author of the study. He is a Postdoctoral Researcher at UHN.
Dr. Markus Selzner is the co-senior author of the study. He is a Scientist at UHN and a Professor in the Department of Surgery at the University of Toronto.
Dr. Lisa Robinson is the co-senior author of the study. She is a Senior Scientist in the Cell and Systems Biology program at the SickKids Research Institute, Professor in the Departments of Paediatrics and Biochemistry, and Institute of Medical Science, and Dean of the Temerty Faculty of Medicine at the University of Toronto.
For a list of competing interests, please see the manuscripts.
These works were supported by UHN Foundation.
Keshavjee S, Sage AT, Borrillo T, Yeung JC, Piyasena D, Wakeam E, Donahoe L, Waddell TK, de Perrot M, Pierre A, Balachandran S, Ghany R, Ali A, Yasufuku K, Cypel M. One thousand cases of ex vivo lung perfusion for lung transplantation: A single-center experience. J Thorac Cardiovasc Surg. 2025 Sep 3:S0022-5223(25)00738-X. doi: 10.1016/j.jtcvs.2025.08.036. Epub ahead of print.
Calderon Novoa F, Chu TP, Lees K, Ganesh S, Martinez-Arenas L, Pollman N, Parmentier C, Kawamura M, Hobeika C, Ray S, Nogueira E, John R, Gupta A, Loizides P, Allen T, Reichman T, Robinson L, Selzner M. Kidney storage at subzero temperature is safe for porcine kidney autotransplantation: A world first in vivo study. Am J Transplant. 2025 Sep 9:S1600-6135(25)02947-8. doi: 10.1016/j.ajt.2025.08.033. Epub ahead of print.
Researchers from UHN’s KITE Research Institute (KITE), in collaboration with the Praxis Spinal Cord Institute, have found that, when all patients receive optimal care, biological sex does not significantly influence recovery after traumatic spinal cord injury. These findings reinforce the importance of ensuring equitable access to evidence-based treatment protocols to support consistent outcomes.
Traumatic spinal cord injury can lead to long-term disability and complex health care needs. Males are more likely to experience these injuries, often due to greater exposure to high-risk activities. However, biological differences between sexes, such as the influence of hormones, have raised questions about sex-based differences in recovery. Age-related hormonal changes, particularly in females, may also play a role in differences in recovery outcomes.
Previous studies have suggested that sex hormones, such as estrogen and progesterone, may help protect nerve cells and reduce inflammation, but clinical findings have been inconsistent.
To explore this further, a research team led by Dr. Julio Furlan, a KITE Scientist, analyzed health data from 1,968 individuals in a Canadian spinal cord injury registry (the Rick Hansen Spinal Cord Injury Registry). The study explored access to care and recovery outcomes between males and females, grouping participants by biological sex, age, and injury severity. Age categories were designed to reflect female hormonal stages: premenopausal (up to 40 years), perimenopausal (41–50 years), and postmenopausal (over 50 years).
The study found that males and females had comparable access to standard treatments, including rehabilitation services, specialized spine centres, and clinical assessments to measure neurological function and nerve recovery. Across all age groups, there were no significant differences in survival rates, neurological recovery, or the ability to regain independence.
Interestingly, females up to the age of 40 years were more likely to undergo surgical treatment than males with similar injury severity. While this did not lead to differences in recovery outcomes, further research is needed to understand whether non-clinical factors, such as unconscious bias, may influence treatment decisions.
Overall, the study highlights that when access to care is equitable, recovery outcomes are consistent across sexes. These findings support ongoing efforts to improve access to high-quality care and promote inclusive research that reflects the diversity of individuals affected by spinal cord injury.
Dr. Julio Furlan, Scientist at UHN’s KITE Research Institute, is the lead author of the study. Dr. Furlan is also an Associate Professor at the Department of Medicine at the University of Toronto.
This work was supported by the Praxis Spinal Cord Institute, with operational support provided by UHN Foundation to the KITE Research Institute.
Furlan JC, Shen T, Kurban D. Effects of Biological Sex on Access to Care and Outcomes After Acute Spinal Cord Injury: A Series of Propensity Score-Matched Cohort Studies. Neurology. 2025 Sep 9. doi: 10.1212/WNL.0000000000213996.
Hand function is central to independence and quality of life, yet current rehabilitation and clinical assessments rarely capture the complexity and variability of real-world hand use. Researchers at UHN’s KITE Research Institute are using AI to assess hand movements in individuals with spinal cord injury—an approach that could lead to tailored rehabilitation strategies with real-world applications.
The research team analyzed hand movements in 19 individuals with cervical spinal cord injuries using home-based video recordings. Participants wore small cameras while performing everyday tasks like cooking, cleaning, or getting dressed. These point-of-view videos showed how people used their hands in natural settings. AI was then used to study the footage and group similar hand movements together.
Unlike traditional assessments conducted in controlled clinical settings with standardized objects, this approach used deep learning models—a type of AI capable of recognizing complex patterns—to identify each person’s unique grasping styles. The AI looked at both posture data (how the hand is shaped) and appearance data (what the hand is interacting with) to identify common grasping patterns. The model was able to group similar movements with 68% accuracy, showing how people adapt their hand use after injury.
This personalized analysis provides clinicians and rehabilitation specialists a better understanding of how individuals adjust their hand movements in daily life. It could help design rehabilitation programs and technologies that focus on hand function used at home. This method may also be useful in fields such as robotics, sports science, and ergonomics, where understanding hand movement is essential.
Dr. Mehdy Dousty, first author of the study, was a former PhD candidate in the labs of Drs. Jose Zariffa and David Fleet.
Dr. Jose Zariffa, senior author of the study, is a Senior Scientist at UHN’s KITE Research Institute (KITE) and holds the KITE Chair in Spinal Cord Injury Research. At the University of Toronto, Dr. Zariffa is an Associate Professor in the Institute of Biomedical Engineering, a Faculty Member of the Rehabilitation Sciences Institute, and a Cross-Appointed Professor in the Edward S. Rogers Sr. Department of Electrical & Computer Engineering.
This work was supported by the Natural Sciences and Engineering Research Council of Canada, Praxis Spinal Cord Institute, the Ontario Ministry of Colleges, Universities, Research Excellence and Security, Craig H. Neilsen Foundation, Healthcare Robotics (HeRo), the NVIDIA Corporation, and UHN Foundation.
Dousty M, Fleet DJ, Zariffa J. Personalized Video-Based Hand Taxonomy Using Egocentric Video in the Wild. IEEE J Biomed Health Inform. 2025 Sep. doi: 10.1109/JBHI.2024.3495699.
A team led by Dr. Philippe Monnier at UHN’s Krembil Brain Institute (KBI) has uncovered a promising new target that could help limit brain injury following an ischemic stroke—a type of stroke caused by a blood clot.
In a healthy brain, the blood-brain barrier acts like a filter, controlling which substances can enter or leave the brain, thereby protecting the brain from harmful substances. After a stroke, some proteins—like one called RGMa—can change the structure of blood vessel walls in the brain. These changes compromise the vessels’ integrity and make them more permeable, or “leaky”, allowing harmful substances in the blood to enter the brain where they cause damage.
The proteins responsible for these changes must first be activated by enzymes such as pro-protein convertases (PPCs). These enzymes act like a switch to turn on other proteins. While PPC inhibitors have been used in other diseases, and blocking RGMa has shown benefits in stroke models, scientists still don’t fully understand how PPCs affect stroke. Among PPCs, subtilisin kexin isozyme-1 (SKI-1) is one of the least understood, but it may play a key role in how blood vessels respond after stroke.
To study SKI-1’s role, the team used preclinical stroke models and blocked the enzyme with a drug called PF-429242. The results were promising: genes that help keep blood vessels strong became more active, while those linked to damage were turned off. Inhibition of SKI-1 also resulted in reduced cell death and smaller areas of brain tissue damage. Importantly, these changes led to better brain function in models.
Building on these findings, the team also discovered that removing a protein called Neogenin had similar protective effects as blocking SKI-1. Without Neogenin, RGMa couldn’t make the blood vessels leaky.
These findings shed light on the molecular mechanisms that contribute to brain damage after ischemic stroke, specifically the role of RGMa, Neogenin, and SKI-1 in compromising blood-brain barrier integrity. By identifying SKI-1 and Neogenin as potential therapeutic targets, this research opens the door to new treatment strategies aimed at protecting brain tissue and improving cognitive outcomes. With further validation in human studies, these discoveries could pave the way for more effective, targeted therapies that transform stroke recovery and reduce long-term disability.
Dr. Alireza Shabanzadeh is the first author of this study. He is a scientific associate in the Monnier Lab at UHN’s Krembil Brain Institute.
The senior author of this study is Dr. Philippe Monnier, a Senior Scientist at UHN’s Krembil Brain Institute and a Professor in the Department of Physiology in the Temerty Faculty of Medicine at the University of Toronto.
This work was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation, and UHN Foundation.
The authors declare no competing interests.
Shabanzadeh AP, Ringuette D, Syonov M, Wu Q, Tassew NG, Mun EK, Meek A, Lively S, Suntharalingham SE, Mojica M, Olijnyk L, Qiang B, Foltz WD, Reed M, Moya I, Brown C, Feng J, Qin X, Akula PS, Wälchli T, Carlen PL, Alcaide-Leon P, Monnier PP. Inhibition of proprotein convertase SKI-1 prevents blood vessel alteration after stroke. Nat Cardiovasc Res. 2025 Sep;4(9):1094-1113. Epub 2025 Aug 26.
Dr. David Kirsch, Director of the Radiation Medicine Program, Head of the Department of Radiation Oncology, and Senior and Allan Slaight Scientist at UHN’s Princess Margaret Cancer Centre, has been elected to the National Academy of Medicine—one of the highest honours in health and medicine.
Dr. Kirsch was elected as a member for his contributions to advancing the understanding and treatment of sarcomas, a rare and complex group of bone and soft tissue cancers. His research has helped reveal how these tumours develop, spread, and respond to therapies—work that has directly influenced care for patients around the world.
Using sophisticated genetically engineered lab models and human sarcoma cell lines, Dr. Kirsch’s team studies the biological mechanisms of cancer and tests new therapeutic approaches. His research has informed international clinical trials that combine radiation therapy and immunotherapy to improve patient outcomes.
“It’s a privilege to work with such a talented and dedicated team of scientists and researchers, whose accomplishments are recognized by this award.” said Dr. Kirsch. “At UHN’s Princess Margaret Cancer Centre, we have an extraordinary environment where research, education, and patient care come together to advance cancer treatment and to make a difference for patients globally.”
Since joining UHN in 2023, Dr. Kirsch has strengthened the integration of discovery research with clinical care in radiation oncology. Supported by UHN’s collaborative research ecosystem and state-of-the-art infrastructure, his work continues to build bridges between laboratory discoveries and better outcomes for patients.
Peter and Shelagh Godsoe Chair in Radiation Medicine, Dr. Kirsch is recognized internationally as a leader in sarcoma research and clinical care. Over his career, he has mentored more than 60 trainees and received multiple awards for research excellence and mentorship.
The National Academy of Medicine elected 90 regular members and 10 international members this year, bringing its total membership to more than 2,500. Members are chosen by their peers for exceptional professional achievement and commitment to advancing health and medicine.
Dr. Kirsch’s election reflects not only his personal accomplishments, but also UHN’s global leadership in cancer research, innovation, and care.
Read the full announcement here.
Researchers at UHN’s Princess Margaret Cancer Centre (PM) have identified a new target that could enhance the effectiveness of radiation therapy for small cell lung cancer (SCLC).
SCLC is an aggressive form of lung cancer, and most patients are diagnosed when the disease is already at an advanced stage, when treatment options are limited. The current standard of care includes chemotherapy and immunotherapy. While initial response rates are often high, many patients relapse due to acquired treatment resistance.
Radiation therapy, when used in combination with chemotherapy (and sometimes immunotherapy), can improve survival for some patients. This benefit might be further enhanced by combining radiation therapy with drugs called radiosensitizers, which increases cancer cells' vulnerablity to radiation.
To identify potential radiosensitizers for SCLC, researchers led by Dr. Benjamin Lok, Clinician Scientist at PM, performed a genetic screen using a gene-editing tool called CRISPR to create mutations in genes of known cancer drug targets.
From this screen, the gene HDAC3 (histone deacetylase 3) emerged as a promising candidate. HDAC3 encodes a protein involved in modifying DNA and regulating gene expression, DNA replication, and repair. It is also known to be implicated in various cancers, including gastric and ovarian cancers.
When researchers removed HDAC3 function, either by silencing the gene or using a drug called RGFP96, SCLC cells became more sensitive to radiation. This radiosensitizing effect was also observed in cancer models, where tumour growth was inhibited.
The team also explored the mechanism underlying HDAC3’s role in radiation sensitivity. They found that loss of HDAC3 resulted in DNA that was more accessible, or open, to radiation, leading to increases in DNA damage. These cells also had more DNA breaks and a reduced ability to repair them, resulting in persistent damage.
Together, these findings suggest that targeting HDAC3 could improve the effectiveness of existing cancer treatments for SCLC, potentially serving as a radiosensitization strategy.
Ujas A. Patel, is a former Master’s student at the University of Toronto and co-first author of the study.
Mary Y. Shi, is a former Master’s student at the University of Toronto and co-first author of the study.
Dr. Benjamin Lok, Clinician Scientist at UHN's Princess Margaret Cancer Centre and Associate Professor in the Department of Medical Biophysics, Radiation Oncology, and Institute of Medical Science at the University of Toronto, is the corresponding author of the study.
This work was supported by the Terry Fox Research Institute, Canada Foundation for Innovation, Cancer Research Society, Canadian Institutes of Health Research, National Cancer Institute, Clinical and Translational Science Center at Weill Cornell Medical Center/Memorial Sloan Kettering Cancer Center, Government of Ontario, and The Princess Margaret Cancer Foundation.
Dr. Benjamin Lok reports institutional grants from Pfizer and institutional grants, personal fees, and nonfinancial support from AstraZeneca, and personal fees from Daiichi-Sankyo outside the submitted work. For a complete list of competing interests, see the manuscript.
Patel UA, Shi MY, Kazan JM, Nixon KCJ, Ran X, Nair SN, Huang O, Song L, Aparnathi MK, He MY, Bakhtiari M, Krishnan R, Hessenow RK, Philip V, Ketela T, Jendrossek V, Hakem R, He HH, Kridel R, Lok BH. CRISPR Screen Identifies HDAC3 as a Novel Radiosensitizing Target in Small Cell Lung Cancer. Mol Cancer Ther. 2025 Sep 25:OF1-OF13. doi: 10.1158/1535-7163.MCT-24-0861. Epub ahead of print.
In a new study from UHN, researchers used machine learning models to predict the severity of chronic thromboembolic pulmonary hypertension (CTEPH)—a rare but treatable condition where there is abnormally high blood pressure in the lungs due to old blood clots and scar tissue. Their findings could help clinicians better assess risk and guide treatment.
CTEPH can develop after a pulmonary embolism (PE)—a blood clot that travels to the lungs. The condition can be cured with surgery, known as pulmonary endarterectomy, which removes the old clots and scar tissue.
To decide if a patient is a good candidate for this surgery, clinicians rely on CT Pulmonary Angiogram (CTPA) scans to assess the extent and location of the blockages. However, current methods for analyzing CTPA results, such as scoring blood vessel obstruction, are not reliable for predicting the severity of the patient’s disease.
To address these gaps and re-examine the link between PE and CTEPH, researchers tested whether machine learning, a form of AI that finds patterns in data, could use detailed blood clot data from CTPA scans to find better links to severe lung high blood pressure (pulmonary hypertension) observed in patients with CTEPH.
The team studied 184 patients with CTEPH who had surgery at UHN between 2017 and 2022, led by Dr. Marc de Perrot, Senior Scientist and Thoracic Surgeon and Dr. Laura Donahoe, Thoracic Surgeon. They found that about 22% of patients had severe pulmonary hypertension. As in earlier studies, the amount of clotting seen on scans alone did not predict how severe the pulmonary hypertension was.
Instead, the most reliable indicator was the right-to-left ventricle ratio—a simple and easy-to-use measurement comparing the size of the heart’s two main pumping chambers. A ratio above 1.4 was strongly associated with severe disease.
The machine learning models tested were also able to identify severe cases of CTEPH by combining this heart measurement with factors such as patient age, sex, and blood clot details from the CTPA scans. This shows that multiple factors influence how serious the condition becomes.
For radiologists, clinicians, and patients, these results provide a new reference point to help identify patients with severe disease and highlight how combining imaging data and machine learning can support better care.
Dr. Micah Grubert Van Iderstine, a former medical student at the University of Manitoba and current resident in the UBC Diagnostic Radiology Residency Program, is the first author of the study.
Dr. Micheal McInnis is a Clinician Investigator at UHN and Assistant Professor in the Department of Medical Imaging at the University of Toronto. He is the corresponding author of this study.
This work was supported by UHN Foundation.
Dr. Micheal McInnis receives speaker fees from Boehringer Ingelheim and AstraZeneca (ongoing) and formerly sat on an advisory board for Boehringer Ingelheim and AstraZeneca (concluded).
Grubert Van Iderstine M, Kim S, Karur GR, Granton J, de Perrot M, McIntosh C, McInnis M. Utility of machine learning for predicting severe chronic thromboembolic pulmonary hypertension based on CT metrics in a surgical cohort. Eur Radiol. 2025 Aug 23. doi: 10.1007/s00330-025-11972-9. Epub ahead of print.
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