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An international source for discovery, education and patient care.
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State-of-the-art research facilities in the heart of downtown Toronto.
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University Health Network (UHN) is a research hospital affiliated with the University of Toronto and a member of the Toronto Academic Health Science Network. The scope of research and complexity of cases at UHN have made it a national and international source for discovery, education and patient care.

Recent News

New Molecular Clues to Artery Health

Study finds that maintaining endothelial cell identity protects arteries from plaque buildup.

Image Caption: Endothelial cells that line arteries help protect against plaque buildup. Over time, factors such as improper blood flow and cholesterol accumulation can damage these cells, causing them to change in ways that contribute to atherosclerosis.

Atherosclerosis, a narrowing of the arteries caused by plaque buildup, can lead to stroke and heart attack. In a new study published in Nature Communications, researchers at UHN’s Peter Munk Cardiac Centre (PMCC) show that the protein ERG (ETS-related gene), which regulates gene activity, helps protect blood vessel cells, called endothelial cells, from changing their identity to a highly migratory cell type that can promote atherosclerosis.

The plaques that cause atherosclerosis are made up of cholesterol and inflammatory cells. Endothelial cells, the thin layer of cells that line the inside of blood vessels, perform many functions that guard against plaque buildup. Lining the 96,000 kilometers of blood vessels in the human body, endothelial cells have a vital role to play in preventing cardiovascular disease.

In parts prone to plaque buildip, this endothelial cell lining becomes damaged, allowing fats and immune cells to accumulate and form the artery-clogging plaques. At the cellular level, endothelial cells undergo a transition where they lose their typical identity and adopt features of migratory cells, called mesenchymal cells. This identity change is called the endothelial-to-mesenchymal transition (EndMT). Although this cell transformation has been linked to atherosclerosis, scientists still do not fully understand how it contributes to blood vessel damage and plaque buildup.

The protein ERG is a key regulator of endothelial cell function by controlling the expression of genes that define their identity, reducing inflammation, and supporting the growth of new blood vessels. Previous studies have linked ERG with EndMT. However, the role of ERG in atherosclerosis has yet to be examined.

Researchers at PMCC investigated the role of ERG using laboratory models of atherosclerosis in which ERG expression was removed from endothelial cells. They found that without ERG, there was a signficiant increase in plaque buildup in these lab models with high cholesterol.

Without ERG, endothelial cells began to lose their normal characteristics and transformed into mesenchymal cells through EndMT. These altered cells migrated into plaques and expanded to promote artery disease.

The loss of ERG also weakened the connections between endothelial cells, which serve as important barrier between the blood and tissues, enabling more cholesterol and fat to enter the arteries. This led to an increase in the accumulation of cholesterol-containing cells in areas normally resistant to plaque formation.

These findings were supported by analyses of human plaque samples, where ERG expression was reduced in cells that appeared to be migrating into plaques, suggesting that loss of ERG may be an early change in a disease process develops over decades. Additionally, restoring ERG in endothelial cells reversed many of the harmful changes and helped the cells regain their normal endothelial identity.

The researchers conclude that ERG acts as a key regulator of blood vessel health. By preventing endothelial cells from losing identity and undergoing EndMT, ERG may help slow or limit the development of atherosclerosis, raising the possibility of future therapeutic approaches.

Dr. Steven R. Botts is an MD PhD student at the University of Toronto and completed this work while a Physician-Scientist Trainee at UHN. He is the first author of the study.

Dr. Kathryn Howe, Scientist at UHN’s Peter Munk Cardiac Centre and Associate Professor, Department of Surgery, University of Toronto, is the co-senior author of this study.

Dr. Jason Fish, Senior Scientist at UHN’s Peter Munk Cardiac Centre and Professor, Department of Laboratory Medicine & Pathobiology, University of Toronto, is the co-senior author of the study.

See www.howeandfishlabs.com for more information about this laboratory.

Medicine by Design, which received funding from the Canada First Research Excellence Fund, the Canadian Institutes of Health Research, the National Institutes of Health, the Ontario Graduate Scholarship Program, the Heart and Stroke Foundation of Canada, the University of Toronto, the Canada Foundation for Innovation, the Foundation to Advance Vascular Cures, the Chan Zuckerberg Initiative, and UHN Foundation.

Botts SR, Scipione CA, Schulz K, Breda LCD, Ellis K, Ho C, Raju S, Prajapati K, Yu K, Khan AB, Polenz CK, Prattas SZ, Hyduk SJ, Cao C, Wythe JD, Robbins CS, Miller CL, Cybulsky MI, Fish JE, Howe KL. ERG preserves endothelial identity to limit atherosclerosis. Nat Commun. 2026 Jul 13;17(1):8615. doi: 10.1038/s41467-026-75287-z.

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A New Avenue for Bipolar Depression

Researchers report rapid symptom relief with repeated ketamine infusions.

Image Caption: A UHN-led trial has found that repeated ketamine infusions reduced symptoms of treatment-resistant bipolar depression without triggering mania or psychosis.

For many people living with bipolar depression, standard treatments do not provide enough relief. Even after trying multiple medications, symptoms can persist, disrupting work, relationships, and daily life. New treatment options are urgently needed.

Researchers led by Dr. Joshua Rosenblat at UHN’s Krembil Brain Institute, Ontario Shores Centre for Medical Health Sciences, and the University of Toronto have found that ketamine may help fill that gap. In a randomized clinical trial published in JAMA Psychiatry, the team found that repeated ketamine infusions significantly reduced symptoms in adults with treatment-resistant bipolar depression.

While ketamine has been studied extensively in major depressive disorders, evidence in bipolar depression has remained limited. Previous randomized trials in bipolar disorder examined only a single infusion. This study is the first randomized controlled trial to evaluate a short course of repeated ketamine infusions for treatment-resistant bipolar depression.

The trial enrolled 68 adults with bipolar I or II disorder who were experiencing a moderate to severe depressive episode despite at least two previous treatment attempts. Participants received four intravenous infusions over two weeks, either ketamine or midazolam, a sedative used as an active comparison treatment. They continued taking their prescribed mood stabilizers or antipsychotic medications throughout the study.

By the end of treatment, participants who received ketamine had significantly lower depression scores than those who received midazolam. More than one-third of participants in the ketamine group met the study's definition of a clinical response, compared with about 12 per cent of those in the comparison group. The benefits continued for approximately one week after the final infusion.

The study also addressed a challenge that has complicated earlier ketamine research. Because ketamine can produce noticeable short-term effects, participants may be able to guess which treatment they received. To help maintain blinding, the researchers used midazolam as an active placebo. Participants identified their treatment assignment only about half the time after the first infusion, suggesting treatment expectations were unlikely to explain the findings.

Equally important were the safety results. Researchers observed no cases of mania, hypomania, or psychosis in either treatment group; concerns that have often limited the use and study of ketamine in people with bipolar disorder.

"Currently available treatments are often ineffective for treatment-resistant bipolar depression, with new treatments urgently needed," says Dr. Rosenblat. "The present trial supports the antidepressant efficacy, safety, and tolerability of serial ketamine infusions for treatment-resistant bipolar depression."

The researchers note that larger studies with longer follow-ups are still needed. However, the findings provide important evidence that ketamine could become an additional treatment option for people living with one of the most difficult-to-treat forms of depression.

Dr. Joshua Rosenblat is a Clinician Investigator in the Poul Hansen Family Centre for Depression, UHN’s Krembil Brain Institute and Centre for Mental Health, and an Associate Professor in the Department of Psychiatry and the Department of Pharmacology and Toxicology at the University of Toronto.

Co-first authors of the study are Diana K. Orsini and Sara Di Luch. The study was conducted by researchers at UHN and Ontario Shores Centre for Mental Health Sciences.

This research was supported by the Canadian Institutes of Health Research and UHN Foundation.

Orsini DK, Di Luch S, Tomlinson G, Lovell G, Vasudeva S, Rodrigues NB, Johnson DE, Flint AJ, Llach CD, McIntyre RS, Mansur RB, Karkouti K, Burhan AM, Kaczmarek E, Chisamore N, Bhatia A, Soneji N, Joshi A, Grewal D, Laframboise R, Rosenblat JD. Serial Ketamine Infusions for Treatment-Resistant Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. Published online September 2, 2026. doi:10.1001/jamapsychiatry.2026.2658.

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A New Class of RNA Therapies

RNA-based approach shows potential for treating genetic diseases like cystic fibrosis.

Approximately 11% of genetic disorders are caused by mutations that prematurely halt messages encoded in DNA. One such condition is cystic fibrosis, a genetic disorder that can result from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In a new study published in Science, researchers at UHN’s Princess Margaret Cancer Centre (PM) developed an RNA-based therapeutic strategy to treat diseases caused by these mutations and successfully corrected a premature CFTR stop mutation in laboratory models.

When DNA is copied into messenger RNA (mRNA), the mRNA is then used as a template to make proteins that carry out the body's functions. Some DNA mutations can create a premature ‘stop’ signal, causing the cell to stop producing a protein too soon, which can contribute to disease. This faulty ‘stop’ signal is called a premature termination codon (PTC).

Therapeutic approaches have been developed to overcome PTCs through engineered molecules known as suppressor transfer RNAs (sup-tRNAs), which can bypass these faulty stop signals and enable the production of full-length, functional proteins. However, engineering safe and effective sup-tRNAs, delivering them efficiently to target cells, and achieving sufficient activity in living cells remain major challenges.

To address these challenges, a team co-led by Dr. Bowen Li, Affiliate Scientist at PM, tested chemical modifications of sup-tRNAs. They identified a modification that increased sup-tRNA stability and efficiency, improved protein production, and reduced unwanted immune system responses.

The researchers also improved delivery of sup-tRNAs to cells by developing a lipid nanoparticle (LNP)—small, lipid-based delivery vehicles that safely carry genetic medicines into cells—specifically tailored to carry sup-tRNAs. Analysis revealed that these LNPs efficiently delivered sup-tRNAs to lung tissue via inhalation.

Cystic fibrosis is a hereditary condition that causes progressive lung damage. Approximately ten percent of patients have mutations that cause a premature ‘stop’ signal and cannot benefit from current therapeutics. The team tested their approach in cystic fibrosis laboratory models and patient-derived tissue samples carrying these mutations and successfully restored the CFTR protein function.

Researchers say the findings could pave the way for a new platform of genetic medicines capable of treating a wide range of diseases caused by mutations that lead to these premature stop signals.

Doctoral Candidate Jingan Chen and Postdoctoral Researchers Dr. Muye Zhou and Dr. Songtao Dong are co-first authors of the study in Dr. Bowen Li’s lab.

Dr. Bowen Li, Affiliate Scientist at UHN’s Princess Margaret Cancer Centre and Associate Professor at the Leslie Dan Faculty of Pharmacy at the University of Toronto, is a co-corresponding author of the study.

Dr. Haissi Cui, Assistant Professor in the Department of Chemistry at the University of Toronto, is a co-corresponding author of the study.

This work was supported by the Leslie Dan Faculty of Pharmacy, the Connaught Fund, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Cystic Fibrosis Canada, Harrington Discovery Institute, the National Institutes of Health, the Government of Canada, Cystic Fibrosis Foundation, PRiME, Next Generation Precision Medicine initiative, and The Princess Margaret Cancer Foundation.

Dr. Li is a Tier 2 Canada Research Chair in RNA Vaccines and Therapeutics and the GSK Chair in Pharmaceutics and Drug Delivery.

Jingan Chen, Dr. Haissi Cui, and Dr. Bowen Li are inventors on an invention disclosure that covers compositions, methods, and uses of the engineered/modified sup-tRNAs. Jingan Chen, Dr. Muye Zhou, Dr. Songtao Dong, and Dr. Bowen Li are inventors on an invention disclosure that covers the described ionizable lipids.

Chen J, Zhou M, Dong S, Gong F, Tennakoon R, Seto BY, Chen ZR, Zhou ZP, Pan J, Xu Y, Luozhong S, Macarios CM, Tijaro-Bulla S, Gonska T, Hu J, Cui H, Li B. Nonviral delivery of chemically modified tRNA rescues nonsense mutations in cystic fibrosis. Science. 2026 Aug 27;393(6814):eaeb0054. doi: 10.1126/science.aeb0054.

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Navigating Uncertainty in ALS

Exploring how people with ALS make care decisions amid uncertainty about symptom progression.

Image Caption: Amyotrophic lateral sclerosis (ALS) is a fast-progressing neurological disease that affects movement and brain function. As symptoms change over time, patients and families often face complex decisions about managing care and maintaining quality of life.

For people living with amyotrophic lateral sclerosis (ALS), everyday activities such as speaking, eating, and swallowing can become increasingly difficult as the disease progresses. Researchers from UHN’s KITE Research Institute, Sunnybrook Health Sciences Centre, and the University of Toronto found that uncertainty about ALS progression can make it challenging for patients to decide when and how to manage their symptoms, highlighting the need for better support and communication from health care providers.

ALS is a progressive disease, and over time, many patients develop bulbar symptoms, which affect speech and swallowing functions. These symptoms are associated with reduced quality of life and can worsen rapidly once they appear. Therefore, early and timely intervention, such as communication aids, dietary changes, or feeding tubes, may help patients maintain function and independence. However, the unpredictable nature of ALS can make it difficult for patients to know when to act.

To better understand these challenges, the research team interviewed 12 adults with ALS, including people with and without bulbar symptoms. Using in-depth interview techniques, the researchers explored how patients approached decisions about symptom management and what support they wanted from health care professionals.

After analyzing participant responses, three key themes emerged: disease uncertainty; quality of information; and personal values and beliefs. Uncertainty about when symptoms might appear or worsen often delayed discussions about treatment options. Some participants preferred to wait until symptoms developed, while others wanted to learn about future options early to plan ahead. Participants also emphasized the importance of receiving clear, personalized information tailored to their individual circumstances, including how symptoms might progress and when interventions should be considered. This helped patients feel more prepared to make decisions. Finally, personal values and beliefs played a key role in decision-making. Priorities included maintaining quality of life, preserving independence, supporting family relationships, and reducing burdens on loved ones, which often influenced decisions.

The findings highlight the need for more person- and family-centered ALS care. Providing timely individualized information and incorporating patients’ values and family perspectives may help patients navigate the complex care decisions that come with living with ALS.

Anna Huynh, first and corresponding author of the study, is a PhD Candidate at the Rehabilitation Sciences Institute at the University of Toronto in the lab of Dr. Yana Yunusova.

Dr. Yana Yunusova, senior author of the study, is a Senior Scientist at UHN’s KITE Research Institute and the Sunnybrook Research Institute. Dr. Yunusova is also a Professor in the Department of Speech-Language Pathology and Director of the Rehabilitation Sciences Institute at the University of Toronto.

This work was supported by the National Institutes of Health, KITE-Toronto Rehabilitation Institute, Fondation Vincent Bourque, ALS Canada, and Brain Canada. Operational support for the KITE Research Institute was provided by UHN Foundation.

The research team is grateful to the research participants—patients living with ALS—as well as ALS neurology partners, Drs. Lorne Zinman and Agessandro Abrahao.

Huynh A, Cranley L, Barnett-Tapia C, Abrahao A, Zinman L, Yunusova Y. Understanding patients' experiences and needs around decision-making for bulbar symptom management at a multidisciplinary ALS clinic. Disabil Rehabil. 2026 Jul 1. doi: 10.1080/09638288.2026.2693395.

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Shaping Canadian Health Sciences

Four UHN researchers elected as Fellows of the Canadian Academy of Health Sciences.

Image Caption: (Pictured clockwise from the top left) Drs. Niall Ferguson, Jennie Johnston, Gang Zheng, and Michael Milosevic.

Four UHN researchers were elected as Fellows of the Canadian Academy of Health Sciences (CAHS)—one of the highest honours in Canadian health sciences. Fellows are nominated from diverse disciplines and recognized for excellence in advancing academic research and improving health and health systems in Canada.

Congratulations to the following UHN researchers, who were among the 59 newly elected Fellows:

● Dr. Niall Ferguson is a Senior Scientist at UHN’s Lung and Respiratory Research Institute. His research focuses on improving outcomes for patients with acute respiratory failure, largely through clinical trials of mechanical ventilation and extracorporeal life support strategies, which temporarily support blood oxygenation outside the body.

● Dr. Jennie Johnstone is a Clinician Investigator at UHN’s Organ Systems and Integrated Health Sciences Research Institute. Her primary area of research is the prevention of hospital-acquired infections.

● Dr. Michael Milosevic is a Clinician Scientist at UHN’s Princess Margaret Cancer Centre. His research examines how advanced, image-guided radiotherapy and biological targeting of hypoxia (low oxygen levels within tumours) and the tumour microenvironment can improve outcomes for patients with gynecologic cancers.

● Dr. Gang Zheng is a Senior Scientist and Associate Research Director at UHN’s Princess Margaret Cancer Centre. Working in the field of cancer nanomedicine, his research develops innovative imaging, diagnostic, and targeted treatment technologies to advance precision cancer care.

For a full list of the 2026 CAHS Fellows, read the press release here.

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Improving Gene Editing Efficiency

New AI method can predict the performance of CRISPR gene editing tools.

Image Caption: CRISPR-Cas9 is a gene-editing tool that enables scientists to modify DNA. The system works by using a short piece of RNA to acts as the guide, directing the Cas9 enzyme to a specific spot where it can cut the DNA.

A study from UHN’s Princess Margaret Cancer Centre (PM) introduces a new AI model that can help scientists design more efficient gene editing tools.

Gene editing enables scientists to make targeted changes to DNA in living cells. These approaches are widely used in biomedical research and have potential applications in treating disease, including correcting disease-causing mutations, identifying potential drug targets, and investigating gene function.

The CRISPR-Cas 9 system is one of the most widely used gene editing tools and uses a short piece of RNA, known as single-guide RNA (sgRNA), to direct the Cas9 protein to a specific location in the genome, where it can cut DNA. However, not all sgRNAs perform equally well, and predicting which guides will be most effective remains a challenge.

As the sequence of the sgRNA affects its gene editing performance, careful guide design is essential. Several AI models have been developed to help predict which RNA sequences will work best. However, these programs often function as "black boxes”, providing little information about how the models work. They also often overlook how the position of patterns within sgRNA sequences influences their effects on Cas9.

To address this problem, the team, co-led by Dr. Sushant Kumar, Scientist at PM, and collaborators developed DeepCC9, a new machine learning framework designed to be both accurate and interpretable. The model identifies position-based sequence patterns for sgRNAs that affect gene editing efficiency. DeepCC9 enables users to learn what sequence features drive this predictive performance.

When tested using datasets for different Cas9 variants, DeepCC9 outperformed existing approaches in predicting how well gene editing would perform. In addition, the researchers identified 74 informative features of sgRNA sequences associated with the prediction of Cas9 genome-editing efficiency. They also found that the position of these features within an sgRNA can significantly affect how well Cas9 binds to and cuts DNA.

These findings provide a clearer picture of the sequence features that contribute to successful gene editing and could help scientists design more effective sgRNAs for research and biotechnology applications. DeepCC9 may help accelerate discoveries in genome engineering and other areas of molecular biology.

Nasim Bakhtiyari, doctoral candidate at Tabriz University of Medical Sciences, is the first author of the study.

Dr. Yosef Masoudi-Sobhanzadeh, from the Department of Computer Engineering, Istanbul Rumeli University and the Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, is a co-corresponding author of the study. He was a Postdoctoral Researcher at UHN’s Princess Margaret Cancer Centre at the time of this study.

Dr. Safar Farajnia, Professor of Biotechnology, Drug Applied Research Center & Biotechnology Research center, Tabriz University of Medical Sciences, is a co-corresponding author of the study.

Dr. Sushant Kumar, Scientist at UHN’s Princess Margaret Cancer Centre and Assistant Professor in the Department of Medical Biophysics at the University of Toronto, is the co-corresponding author of the study.

This work was supported by the Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Drug Applied Research Center, and Tabriz University of Medical Sciences.

Dr. Sushant Kumar is a Tier 2 Canada Research Chair in Genomic Medicine.

Bakhtiyari N, Masoudi-Sobhanzadeh Y, Farajnia S, Kumar S. An interpretable deep learning framework uncovers features governing CRISPR-Cas9 genome-editing efficiency. Bioinformatics. 2026 Jul 2;42(7):btag483. doi: 10.1093/bioinformatics/btag483.

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Celebrating Transplant Research

UHN’s Ajmera Transplant Centre Research Day was a showcase of discovery and collaboration.

Image Caption: Moments from Ajmera Transplant Centre Research Day, featuring scientific sessions, participant engagement, and award recipients.

UHN’s Ajmera Transplant Centre (ATC) brought the transplant community together for its annual Research Day, an energizing forum that spotlighted the ideas, collaborations, and people driving progress in solid-organ transplantation.

Close to 200 clinicians, scientists, trainees, patient partners, and health professionals filled the Transplant Innovation Centre for a day designed to spark discussion and accelerate discovery. The program featured four scientific sessions: New Horizons in Transplantation, Innovations in Transplantation, Nursing, Health Disciplines and Quality Improvement, and Clinical Research at Ajmera Transplant Centre.

The day featured an exciting lineup of speakers, including keynote presenter Dr. Alireza Rabi, cardiac surgeon and Affiliate Scientist at UHN's Peter Munk Cardiac Centre, who shared how innovation in donor heart recovery, preservation, and repair can expand access to heart transplantation. Four invited experts and six recipients of Ajmera grants and fellowships also presented emerging findings that point to new opportunities for impact.

The breadth and depth of transplant research at UHN were on full display through 39 electronic posters and 39 printed posters. Judges recognized Sarayna Bala and Dr. Naga Karthik Enamundram in the Basic/Translational Science category, and Dr. Emmanuel Lafont and Dayana Davoudi in the Clinical Science category.

The event also celebrated the people whose contributions are advancing research, teaching, mentorship, and patient care across the transplant community. Among the award recipients were Dr. Ana Konvalinka and Dr. Juan Montagne, who received the Dr. Gary Levy Award for Excellence in Clinical and Translational Research.

Additional honours recognized excellence in teaching, mentorship, citizenship, and clinical education across faculty, fellows, and health professionals. Dr. Cynthia Tsien and Dr. Melinda Nguyen received the Dr. Paul Greig Award for Excellence in Teaching. The Dr. Heather Ross Award for Exemplary Citizenship and Mentorship in Transplant was awarded to Dr. Vivek Rao and Dr. Mukesh Kumar. Alicia Healey received the Nursing and Health Professions Excellence in Clinical Teaching Award.

Together, the day captured the spirit of ATC: bold science, strong partnerships, and a shared commitment to improving outcomes and quality of life for transplant patients. It also underscored ATC’s leadership in shaping the future of transplant research, education, and care.

The Ajmera Transplant Centre Research Day 2026 was made possible through the generous support of sponsors Astellas, Merck, and Takeda as Gold Sponsors, and Traferox as Silver Sponsor.

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Research Institutes at UHN

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.