Decoding a Rare Genetic Heart Threat

Study reveals how mutations can trigger arrhythmias and cardiac arrest in a rare condition.

Image Caption: In short QT syndrome, the electrical recovery of the heart muscle after each heart beat is accelerated and creates a risk of sudden arrhythmia.

Short QT syndrome (SQTS) is a rare, inherited condition that can cause sudden cardiac death. A new study from UHN, the University of Toronto, and collaborators in Germany provides insight into the molecular mechanisms behind SQTS using patient-derived lab models.

In SQTS, problems with the heart’s electrical system increase the risk of heart rhythm problems, called arrhythmias, which can lead to sudden death. Despite improved awareness and diagnosis of SQTS over the years, scientists still do not entirely understand the underlying molecular causes or how to optimally treatment the condition.

Several genes have been implicated in this condition, including SLC4A3 (Solute Carrier Family 4 Member 3)—involved in mediating the exchange of ions (charged atoms) across cell membranes and, ultimately, the pH inside cells. However, analyses of mutations in SLC4A3 have yet to explain how altered pH leads to arrhythmias and cardiac death.

To address this knowledge gap, the team examined two new SLC4A3 mutations by generating lab-grown models of cardiomyocytes—heart muscle cells—from patient samples. They found that in models with mutated SLC4A3, the disruption of ion movement across the cell membrane caused the cells to have a higher pH or be more alkaline. The increased pH resulted in a fewer calcium ions moving into the cells, which led to the shortening of the heart’s electrical recovery after each heart beat and irregular, arrhythmia-like beating.

This study reveals, for the first time, the mechanisms underlying SQTS related to pH imbalance and how SLC4A3 gene mutations lead to heart problems. These findings open the door to potential new, targeted drug treatments.

Dr. Michael Gollob is a Senior Scientist at UHN and a Professor in the Department of Physiology in the Temerty Faculty of Medicine at the University of Toronto. He is the co-senior author of this study.

Dr. Ibrahim Akin, from the University Medical Centre Mannheim (UMM), University of Heidelberg, and Dr. Ibrahim El-Battrawy, from Ruhr University Bochum, are also co-senior authors of the study.

The first authors of the study are:

● Zenghui Meng – University Medical Centre Mannheim (UMM), University of Heidelberg

● Chen Yan – University Medical Centre Mannheim (UMM), University of Heidelberg

● Christina Holscher – University Medical Centre Mannheim (UMM), University of Heidelberg

● Boldizsar Kovacs – Inselspital University Hospital of Bern

● Saltanat Zhazykbayeva – Ruhr University Bochum

● Oliver Jarkas – Ruhr University Bochum

This work was supported by the Ian Copland Arrhythmia and Sudden Death Research Fund at the University of Toronto, the German Center for Cardiovascular Research, the Hector- Stiftung, Else-Kröner-Fresenius Foundation, German Heart Foundation, EU Horizon 2020 research and innovation program, and UHN Foundation.

See the manuscript for competing interests.

Meng Z, Kovacs B, Yan C, Hölscher C, Zhazykbayeva S, Jarkas O, Zou C, Cyganek L, Zorio E, Braza-Boils A, Pablo Ochoa J, Rehbehn N, Fan X, Lei X, Liu R, Tong S, Liu F, Xue Z, Bober SL, Zhao B, Duru F, Aweimer A, Köppel A, Burau K, Mügge A, Berger W, Hamdani N, Zhou X, Saguner AM, Akin I, Gollob MH, El-Battrawy I. SLC4A3-related short QT syndrome assessed in human induced pluripotent stem cell-derived cardiomyocytes: mechanisms of ventricular arrhythmia and sudden cardiac death. Eur Heart J. 2026 Mar 5:ehag068. doi: 10.1093/eurheartj/ehag068. Epub ahead of print.

Canadian Honour for Chem Innovator

UHN researcher awarded SCI’s Canada Medal for lifetime contributions to biotech and pharma.

Image Caption: Dr. Donald Weaver is a Senior Scientist at UHN’s Krembil Brain Institute, a Professor of Neurology at the University of Toronto’s Temerty Faculty of Medicine, and a Professor (Status Only) in the Department of Chemistry at the University of Toronto.

The Society of Chemical Industry (SCI) has awarded its Canada Medal to Dr. Donald Weaver, Senior Scientist at UHN’s Krembil Brain Institute, recognizing his productive career translating chemistry into real-world health solutions. 

The SCI Canada Medal recognizes a scientific business leader whose lifetime contributions have advanced a Canadian industry rooted in chemistry, including fields such as biotechnology and pharmaceuticals, two areas in which Dr. Weaver has had lasting global impact. 

Dr. Weaver is internationally recognized for his research focused on understanding and treating Alzheimer disease (AD). His commitment to medicinal chemistry is rooted in his clinical experience—he is among a small handful of people worldwide with credentials as a medicinal chemist and neurologist. His first encounter with a patient with AD in 1981 sparked a lifelong determination to design drugs capable of altering the course of the condition. Dr. Weaver’s more than 40-year career, grounded in both chemistry and neuroscience, has bridged molecular science, drug development, and patient care.  

“Papers are nice. Products are nicer. Canadian products are nicest of all,” says Dr. Weaver. This motto reflects his philosophy that research should not stop at publications but move decisively toward solutions that benefit patients. 

Throughout his illustrious career, Dr. Weaver has sat at the helm of several innovative organizations. In 1994, Dr. Weaver co‑founded Neurochem Inc., which later became Bellus Health, in Montreal. Here he invented two amyloid-targeting drugs that both eventually went to phase 3 clinical trials: tramiprosate—one of the first drugs ever tested with the intent to modify the disease course of AD—and eprodisate. In 2023, GlaxoSmithKline (GSK) acquired Bellus Health for approximately $2 billion.  

In Halifax in 2006, Dr. Weaver co‑founded DeNovaMed Inc. to develop novel antibiotics. He continues to serve as their Chief Medical Officer.  

Most recently, Dr. Weaver co‑founded Treventis Corporation in Toronto, a spin‑out from his UHN laboratory, where he also serves as Chief Medical Officer. In 2023, Treventis entered a major collaboration and licensing agreement with Takeda to advance small‑molecule therapies targeting toxic tau protein in AD.  

Beyond commercial work, Dr. Weaver has authored more than 400 peer‑reviewed publications, including Medicinal Chemistry (Oxford University Press), a widely used reference in the field. He holds 47 patents, all focused on therapeutic applications. He has received numerous honours for his work, including the Bernard Belleau Award in Medicinal Chemistry, the Merck Frosst Award in Organic Chemistry, and the Oskar Fischer Prize. The SCI Canada Medal adds a distinct recognition celebrating the translation of fundamental science to industry. 

“I am genuinely thrilled to receive the SCI Canada Medal,” says Dr. Weaver. “I have spent my career working at the interface between chemistry and clinical neurology, which is not a typical place to stand; you are never quite sure whether your feet are planted in chemistry or medicine. Recognitions are usually discipline specific, so it is especially meaningful to receive this award from a chemistry society that values translation and real-world outcomes.” 

New Drug for Kidney Health

Trial finds finerenone improves kidney health in adults with diabetes & kidney disease.

Results of an international clinical trial, where UHN was a Canadian site, showed that the drug finerenone may help improve kidney health in adults with type 1 diabetes and chronic kidney disease (CKD).  

Type 1 diabetes affects approximately 9.5 million people worldwide. CKD—the long-term and progressive loss of function in the kidneys—remains a common and serious complication of type 1 diabetes. Some drugs, like finerenone—which blocks the activity of certain hormones that can damage the heart and kidneys—have been shown to help people with CKD caused by type 2 diabetes. But until now, these medications haven’t been used in clinical trials in people with type 1 diabetes and kidney disease.

To address this, a team of international researchers ran a clinical trial to test finerenone on 242 adults with type 1 diabetes and CKD. Dr. David Cherney, Senior Scientist at UHN and Professor at the University of Toronto’s Temerty Faculty of Medicine, was the lead investigator at the UHN site in Toronto.

Published in The New England Journal of Medicine, results showed that participants receiving finerenone had a significantly greater decrease in the urinary albumin-to-creatinine ratio than those who received the placebo, suggesting kidney protection with finerenone. Healthy kidneys prevent albumin—a type of protein in the blood—from being excreted in the urine, resulting in a lower ratio. Therefore, a reduction in urinary albumin levels is consistent with a lower risk of developing worsening kidney disease.

These findings highlight the potential of finerenone as an additional therapeutic option for adults with type 1 diabetes and CKD. More research will be needed to understand long-term effects on diverse populations.

This study was led by the FINE-ONE Investigators, including the following authors:

• Hiddo Heerspink, Andreas Birkenfeld, David Cherney, Helen Colhoun, Per-Henrik Groop, Linong Ji, Niels Jongs, Chantal Mathieu, Richard Pratley, Sylvia Rosas, Peter Rossing, Jay S Skyler, Katherine Tuttle, Robert Lawatscheck, Meike Brinker, Markus Scheerer, Julie Russell, Patrick Schloemer, and Janet B McGill

Dr. David Cherney is a Senior Scientist at UHN and Professor in the Department of Medicine at the University of Toronto. He is also the Gabor Zellerman Chair of Nephrology Research at the University of Toronto. He was a member of the international steering committee for the trial and the lead investigator for the UHN site of the trial.

This study was supported by Bayer.        

Research at UHN is supported by UHN Foundation, and Dr. Cherney was supported by the Canadian Institutes of Health Research.

Heerspink HJL, Birkenfeld AL, Cherney DZI, Colhoun HM, Groop PH, Ji L, Jongs N, Mathieu C, Pratley RE, Rosas SE, Rossing P, Skyler JS, Tuttle KR, Lawatscheck R, Brinker M, Scheerer MF, Russell J, Schloemer P, McGill JB; FINE-ONE Investigators. Finerenone in Type 1 Diabetes and Chronic Kidney Disease. N Engl J Med. 2026 Mar 5;394(10):947-957. doi: 10.1056/NEJMoa2512854.

Fuelling World-Class Research

Provincial government invests more than $2.5 million in projects from UHN researchers.

Image Caption: Recipients of the Ontario Research Fund include (clockwise from top-left) Drs. Mamatha Bhat, Daniel Winer, Jennifer Campos, George Mochizuki, J. Rafael Montenegro Burke, and Kâmil Uludağ.

Six UHN researchers received over $2.5 million in total funding to support research projects improving liver transplant survival, how mechanical force affects immune function, enhancing safer mobility for older adults, reducing fall risk, advancing brain imaging, and accelerating drug discovery.

Through the Ontario Research Fund (ORF), the Ontario government invested over $47 million in 195 research projects from universities, colleges, and research hospitals across the province.

UHN recipients of this funding include the following:

● Mamatha Bhat, Scientist at UHN’s Ajmera Transplant Centre and Assistant Professor at the University of Toronto’s (U of T’s) Temerty Faculty of Medicine, received $396,237 from the ORF Small Infrastructure Fund. This funding will support the advancement of machine learning models to inform precision diagnostics and therapy for liver transplant patients.

● Daniel Winer, Senior Scientist at UHN and Assistant Professor at U of T’s Temerty Faculty of Medicine, received $243,257 from the ORF Small Infrastructure Fund. The funding will support research to understand how the immune system detects and responds to physical changes, like stiffness, in the environment, and how these changes affect immune function. This work could help advance new therapies for disease, improve safety during space travel, and slow the aging process.

● Jennifer Campos, Senior Scientist at UHN’s KITE Research Institute and Professor at U of T’s Temerty Faculty of Medicine, received $408,086 from the ORF Small Infrastructure Fund. The funding will support a research program that uses DriverLab, Canada's most advanced driving simulator, to understand how age-related changes to vision and hearing, cognitive decline, and medication use affect driving performance. The goal of the program is to support safe, independent mobility, inform driving policies, improve vehicle design, and enhance quality of life for older adults.

This funding will be used to cover the cost of state-of-the-art equipment for these critical research projects.

UHN also received more than $1.2 million through projects led by UHN-affiliated Drs. George Mochizuki, Kâmil Uludağ, and J. Rafael Montenegro Burke at collaborating institutions. Dr. Mochizuki, Affiliate Scientist at UHN’s KITE Research Institute and Associate Professor at York University, leads a project that aims to understand markers of fall risk. Dr. Uludağ, Senior Scientist at UHN’s Krembil Brain Institute and Senior Scientist at Sunnybrook Health Sciences Centre, leads a project enhancing the diagnosis and treatment of brain conditions through the acquisition of a new radiofrequency (RF) coil and contrast agent injector for the new 7T MRI scanner. Dr. Montenegro Burke, Affiliate Scientist at UHN’s Princess Margaret Cancer Centre and Principal Investigator at the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research, leads a project that will explore how cancer cells alter metabolism to resist treatment.

“In the face of economic uncertainty, Ontario researchers are bolstering our critical industries with discoveries that cement our province as a global leader,” said Hon. Nolan Quinn, Minister of Colleges, Universities, Research Excellence and Security. “This investment in our world-class colleges, universities and hospitals will advance the sectors that drive our economy, create jobs, and save lives.”

Congratulations to all recipients at UHN!

To read the announcement, click here. To see a full list of funded projects in 2026, click here. 

Imaging the Imagining Brain

Study sheds light on brain activity underlying conscious imaginative processes in athletes.

Image Caption: Visualization, also known as motor imagery, is a common technique used by high-level athletes that involves imagining key movements without physically performing them. This practice is based on the belief that imagined, and real actions activate similar brain regions and that motor imagery may therefore improve athletic performance.

A recent study conducted by a team from UHN’s Krembil Brain Institute (KBI) has revealed the part of the brain responsible for conscious imagining during a process called “visualization” in athletes. Their work could be the first step in revealing the brain activity behind imagination. 

“Imagination plays a critical role in many everyday tasks, yet how the brain generates this process is not well understood," says Dr. Richard Wennberg, senior author of the study and Clinician Investigator at UHN’s Krembil Brain Institute (KBI). "By studying how high-level athletes use visualization techniques to train movement and reactivity, we are able to pinpoint consistent patterns of brain activity, offering new insights into the underlying processes that control imagination.”

High-level athletes, like professional ice hockey players, use motor imagery—also known as visualization—to rehearse movements and train their brain’s ability to perform complex tasks, even when not actively playing a sport. An optimized technique, called PETTLEP (Physical, Environment, Task, Timing, Learning, Emotion, and Perspective), gives players a structured scenario, or script, to guide their visualization practice. While the use of the technique is well established, the underlying brain activity associated with PETTLEP visualization has not been well understood until now.

In a recent study, a KBI team, led by Dr. Wennberg, assessed the brain activity of eight high-level female ice hockey players during PETTLEP visualization using magnetoencephalography (MEG). MEG identifies active parts of the brain by measuring the magnetic signals produced when large groups of neurons in the same area fire simultaneously.

The research team found that the greatest activation during visualization occurred in the back (posterior) of the left hemisphere’s cortex, primarily around the intraparietal sulcus—a fold on the brain’s surface that runs horizontally from the middle to the back of the left hemisphere. This is the first time researchers have identified one specific area activated during visualization. Further, it offers a look at how the brain activity changes millisecond to millisecond. 

Importantly, the activated brain area was consistent in both the goalie and players of other positions, even though the goalie used a different PETTLEP script. This suggests the activation of the posterior left hemisphere cortex may reflect a conscious act of visualization—or imagination itself.

The study’s findings provide preliminary insight into the brain activity associated with visualization, laying the groundwork for future research into imaginative processes. Further studies will be needed to determine whether these results are replicable in non-athletes and extend to other forms of conscious or unconscious imagining, such as dreaming. 

Dr. Audrey Alice Potts, first author of the study, is a Family and Sports Medicine physician at the Mayo Clinic in Rochester, Minnesota, USA.

Dr. Richard Wennberg, senior author of the study, is a Clinician Investigator at UHN’s Krembil Brain Institute, Director of UHN’s Mitchell Goldhar Magnetoencephalography (MEG) Unit, and Professor of Neurology at the University of Toronto’s Temerty Faculty of Medicine.

This work was supported by UHN Foundation

Potts AA, Garcia Dominguez L, Gold D, McAndrews MP, Wennberg R. Complex motor imagery in elite female ice hockey players: a cortical arena of imagination revealed by magnetoencephalography. Front Hum Neurosci. 2026 Feb 27;20:1754371. doi: 10.3389/fnhum.2026.1754371.

Powering Physician Innovation

SUMO and UHN are strengthening physician‑led research to transform care across Ontario.

Image Caption: The SUMO team gathered during a recent planning session focused on supporting clinician‑scientists.

For nearly two decades, SUMO (Sinai‑UHN Medical Organization) has been strengthening Ontario’s academic medicine ecosystem by ensuring physicians have the support they need to transform health care delivery. As the governance organization responsible for administering the Academic Health Science Centre (AHSC) Alternative Funding Plan agreement, SUMO plays a vital role in enabling physicians at Sinai Health and UHN to balance clinical care, education, and research. 

Over the past decade alone, sustained multi‑million‑dollar investment through SUMO’s funding programs has helped clinician‑scientists build an extraordinary record of achievement. With multiple rounds of support totalling about $25 million, investigators have produced more than 8,600 peer‑reviewed publications—research that carries roughly twice the scholarly influence of comparable studies. Within that output, more than 1,860 papers rank among the most highly cited in their fields, highlighting both reach and relevance.

This investment has also generated far‑reaching impact beyond academia. Academic publications from SUMO‑funded investigators have informed more than 3,000 policy documents in 69 countries, shaping major decisions in areas such as infectious disease response, stroke care, and palliative medicine. Together, these results show how sustained, targeted funding for clinician‑scientists can ripple across health systems, improving care locally while influencing practice and policy around the world.

This year marks an exciting first for SUMO: a partnership with Canada Leads to co-fund the SUMO-UHN Distinguished Physician Investigator Award, supporting a single outstanding mid-career physician with a $500,000 salary commitment over five years. Unlike traditional project‑based funding, this award invests in a person, not a proposal—reflecting SUMO’s belief that the most meaningful health care improvements begin with exceptional people.

● Related: Apply now to the SUMO-UHN Distinguished Physician Investigator Award [internal connection required]

SUMO also administers other initiatives under its Innovation Fund program. These initiatives allow physicians across UHN and Sinai Health to pilot new models of care, expand their professional skills, and build capacity for system‑wide change.

The result is a powerful combination of talent, opportunity, and institutional partnership. As one of SUMO’s founding parties, UHN plays a central role in advancing this work by enabling research environments where innovation thrives. Together, SUMO and UHN are cultivating the next generation of clinician‑investigators whose discoveries will shape a more efficient, equitable, and resilient health care system.

With almost two decades of measurable impact behind it and a renewed commitment to physician‑led innovation, SUMO continues to strengthen Ontario’s health care landscape—one investigator, one idea, and one innovation at a time.

Building Fairer AI for Health Care

Researchers propose a framework for more equitable health care AI systems.

Image Caption: As the use of AI in health care grows, there are concerns that AI models trained on real-world clinical data could perpetuate or amplify existing disparities between patient populations. Clinical AI systems must be designed for accuracy but also ensure equitable treatment for all patients.

In a new study, researchers from UHN and North York General examined how AI models can predict race based on clinical notes written by health care providers and how these models can be designed to perform more equitably across race, sex, and age. This research provides insight into developing fair and accurate clinical AI systems.

Racial discrimination in health care plays a significant role in patient outcomes and health care utilization, and there is a need for equity-focused research and care that reflects diverse communities. As digital health tools, like AI, are increasingly used to support clinical care and research, there is a need to ensure that these systems perform consistently across diverse patient populations. If not carefully designed, these systems may amplify existing inequities.

One challenge in addressing bias in clinical AI is the inconsistency of racial data in medical records. Information about a patient's race is often missing or incomplete in electronic health records, making it difficult for researchers to evaluate the performance of AI models for different patient groups.

To better understand these challenges, the research team evaluated how well AI models could predict race from health care providers’ clinical notes. They compared several advanced language models, including a widely used transformer-based system, which analyzes text or images as one continuous section, with another type of model, called a hierarchical convolutional neural network. This model is designed to better reflect the layered structure of clinical notes.

They also applied specific rules to these models to optimize fairness—the ability of AI algorithms to make decisions without prejudice against individuals or groups based on characteristics like race, gender, or age.

The study found that the AI model designed to mirror the structure of clinical notes was more accurate and fairer than the other models. Additionally, including fairness rules helped some AI models perform with less bias across groups, but in others, it reduced accuracy. This showed that fairness tools did not work the same way for every AI system.

The researchers also found that many of the disparities in AI performance seen across patient groups were linked to how the health care providers wrote their notes. This showed that bias in how information is documented can also impact how AI systems interpret and use information.

The study highlights that fairness can be built into clinical AI systems, but approaches must be carefully matched to the model. These findings offer a practical framework for developing more equitable language-based AI tools in health care and underscore the need to address systemic gaps in how health information is recorded.

Dr. Rawan Abulibdeh is a Postdoctoral Researcher at UHN and first author of the study.

Dr. Ervin Sejdić is an Affiliate Scientist at KITE Research Institute and a Professor in the Rogers Sr. Department of Electrical and Computer Engineering at the University of Toronto. He is the Research Chair in Artificial Intelligence for Health Outcomes at North York General, and he is the corresponding and co-senior author of the study.

Dr. Karen Tu, Clinician Scientist at UHN and Professor in the Department of Family and Community Medicine at the University of Toronto. She is also a Research Scientist at North York General and the co-senior author of the study.

This work was supported by the Canadian Institutes of Health Research, the North York General TD Smart Technologies for Early Prediction and Prevention (STEPP) Lab funded by TD Bank Group, the University of Toronto, the National Institute of Health, the National Science Foundation, and UHN Foundation.

Dr. Tu is a Chair in Family and Community Medicine Research in Primary Care at UHN

Abulibdeh R, Lin Y, Ahmadi S, Sejdić E, Celi LA, Zhao Q, Tu K. Integration of fairness-awareness into clinical language processing models. Commun Med (Lond). 2026 Feb 24;6(1):178. doi: 10.1038/s43856-026-01433-9