Empowering Fair and Responsible AI

A team led by Princess Margaret developed AFFRM-AI, a framework for AI in clinical settings.

Image Caption: AFFRM-AI is designed to guide research teams and clinicians on how to responsibly, safely, and compassionately develop and deploy AI solutions for health care.

Health care is increasingly being transformed by AI, with technologies such as medical scan analysis and cancer risk prediction tools enabling faster diagnosis and treatment. Yet, alongside these advancements comes a critical challenge: how do we translate powerful AI methods into safe, trustworthy, and sustainable clinical tools? To address this, UHN’s Cancer Digital Intelligence (CDI), a research and innovation program within the Princess Margaret Cancer Centre, developed AFFRM-AI, a framework for the fair and responsible use of AI tools.

Bridging a Critical Gap: AFFRM-AI

CDI aims to improve cancer care through technology and AI. As such, it has been actively researching the use of AI in medicine since the technology’s early development. One goal of CDI is to promote a culture of fair and responsible AI and take the steps necessary to mitigate bias in AI solutions caused by social, data-related, methodological or algorithmic factors. Despite the growth of AI use, there has been a lack of accessible and actionable resources on the fair and safe use of AI in clinical settings. 

To address this, CDI assembled a 16-member working group composed of leading experts from various institutions in related fields including AI, bias, ethics, privacy, education and medicine to develop a guidance document.

The CDI team developed, A Framework for Fair and Responsible Machine Learning and AI (AFFRM-AI) that outlines best practices and recommendations for two key goals:  

1. Encouraging responsible, safe, and compassionate AI development and deployment within UHN clinics 

2. Safeguarding patients and care providers from biased and inequitable AI predictions.  

AFFRM-AI provides actionable guidance across four key stages: (1) problem identification and study design, (2) model development and training, (3) silent deployment—testing real-world performance observationally without influencing clinical decisions—and clinical evaluation, and (4) operational deployment and ongoing monitoring. Within each stage, the framework provides concrete recommendations, reflective questions, and documentation prompts addressing how data are used and approved, data readiness and availability, how fairness is measured, selection of appropriate outcome measures, and more.

Designed to adapt to local contexts, AFFRM-AI enables multidisciplinary teams—including clinicians, data scientists, privacy experts, ethicists, and operational leaders—to share a common language and set clear expectations for building safe AI systems that are grounded in equity, fairness, scientific rigor, and transparency.

Driving Responsible AI at UHN and Beyond

The AFFRM-AI framework and the methodology behind its development have been published in The Lancet Digital Health.  The team is now focused on cultivating engagement within the UHN community, including working with the Research Ethics Board (REB) and the AI Deployment team, among others, to encourage organization-wide adoption of standards for equitable and responsible AI use.

By providing concrete, operational guidance, AFFRM-AI aims to put responsible AI into practice and protect patients. Initiatives such as this position UHN at the forefront of responsible innovation, ensuring that powerful AI methods and progress translate into safe, trustworthy, and sustainable clinical tools.

For more information and to view the Framework, see here.

The AFFRM- AI Framework was prepared by Mattea Welch, Benjamin Grant, and Christopher Deutschman, in consultation with Clare McElcheran, Adam Badzynski, Jennifer A.H. Bell, Andrew Hope, Robert C. Grant, Tran Truong, Kelly Lane, Patti Leake, Divya Sharma, Ian Stedman, Mike Lovas, Ale Berlin, Jeremy Petch, Benjamin Haibe-Kains, and James A. Anderson.

Work on AFFRM-AI was partly supported by the Associated Medical Services (AMS) Healthcare, CDI and The Princess Margaret Cancer Foundation.

See the manuscript for additional acknowledgements and competing interests.

Welch ML, Grant B, Deutschman C, McElcheran C, Badzynski A, Bell JAH, Hope A, Grant RC, Truong T, Lane K, Leake P, Sharma D, Stedman I, Lovas M, Petch J, Berlin A, Haibe-Kains B, Anderson JA. A practical framework for operationalising responsible and equitable artificial intelligence in health care: tackling bias, inequity, and implementation challenges. Lancet Digit Health. 2026 Mar;8(3):100957. doi: 10.1016/j.landig.2025.100957. Epub 2026 Mar 20.

Hearing, Balance, and Thinking

Cognitive training improves balance and multitasking with varied benefits to hearing ability.

Image Caption: KITE Research Institute’s StreetLab is an immersive virtual reality facility that allows scientists to study complex interactions between sensory and cognitive processes. Study participants navigated a virtual street-crossing environment while simultaneously completing listening, memory, and standing balance tasks. (Image courtesy of KITE Studios)

Igniting a Love of Science

UHN STEM Pathways co-hosted an event as part of the 2026 Science Rendezvous festival.

Image Caption: Volunteers from UHN’s STEM Pathways led participants in hand-on science-based activities.

On Saturday, May 9, 2026, in collaboration with Sinai Health’s SciHigh program, UHN STEM Pathways took part in Science Rendezvous—a free festival celebrating science through interactive STEM (science, technology, engineering, and mathematics) experiences for youth.

The event was held at Sinai Health’s Hennick Bridgepoint Hospital and welcomed over 200 attendees. Visitors explored a wide range of interactive booths led by volunteers from UHN and Sinai Health. Each booth was designed to make science hands-on and accessible.

Participants tried their hand at coding at the robotics & AI station, guiding mini robots through obstacle courses created with 3D printing. At the brain station, others investigated the human body by crafting “brain hats” and testing prosthetic claws powered by muscle signals.

Several activities invited participants to experiment and observe science in action. The Look Closer booth offered attendees an opportunity to look at cheek cells and blood samples under microscopes. Budding scientists also learned lab basics in Pipetting 101, using micropipettes and pH strips, and followed the body’s defenses in the Microbe Maze, a 3D-printed immune system challenge.

Families folded origami hearts and tested their knowledge at the Pumped Up cardiovascular station, and built cell models and explored germ prevention through chemical reactions at the Trick or Treat station. Through fun, interactive games, adults and youth alike identified organs and body systems.

Together, the interactive booths created an engaging environment where youth could explore science through creativity, experimentation, and play.

This event was made possible by the hard work of UHN and Sinai Health volunteers. Through Science Rendezvous, UHN STEM Pathways emphasizes the value of making science more accessible. 

UHN STEM Pathways is a Toronto-based outreach program that aims to inspire and educate students from kindergarten to grade 12 through interactive tours, scientist panels, hands-on workshops, and classroom visits. For more information on their current offerings, click here or contact stempathways@uhn.ca.

Investing in Research and Innovation

Six UHN researchers receive funding through new or renewed Canada Research Chairs.

The Government of Canada has announced the latest round of funding for the Canada Research Chair (CRC) program. Nearly $140 million will support 165 new and renewed CRCs.

Congratulations to the following UHN researchers who received new or renewed funding from the CRC program:

● Dr. Valerie Wallace, Tier 1 Canada Research Chair in Retina Regeneration (renewal). Dr. Wallace is a Senior Scientist and Research Director at UHN’s Donald K. Johnson Eye Institute and a Professor in the Department of Ophthalmology and Vision Sciences at the University of Toronto (U of T). Dr. Wallace’s research focuses on understanding retinal regeneration and tumour initiation in the brain—work that may uncover new therapeutic targets and strategies for vision loss and brain cancers.

● Dr. Emily Seto, Tier 1 Canada Research Chair in Accessible Virtual Care Innovations (new). Dr. Emily Seto is an Affiliate Scientist at UHN and an Associate Professor at the Institute of Health Policy, Management and Evaluation (IHPME) at U of T. Funding from this Chair will support her research in designing and evaluating virtual care technologies to ensure digital health is accessible for all patients.

● Dr. Shiphra Ginsburg, Tier 1 Canada Research Chair in Health Professions Education (renewal). Dr. Ginsburg is a Clinician Scientist at The Institute for Education Research at UHN, a Clinician Scientist at Mount Sinai Hospital, a Scientist at the Wilson Centre, and a Professor in the Department of Medicine at U of T. Her research advances the knowledge and practice of assessment in medical education, with a particular focus on how clinical supervisors evaluate learner performance, how professionalism is conceptualized and judged across different contexts, and how language, bias, and identity shape the fairness and validity of evaluation of learners and supervisors.

● Dr. Shane Harding, Tier 2 Canada Research Chair in Radiation Biology (new). Dr. Harding is a Senior Scientist at UHN’s Princess Margaret Cancer Centre and an Associate Professor in the Departments of Medical Biophysics, Immunology, and Radiation Oncology at U of T. His research focuses on understanding how to improve DNA-damaging therapeutics, such as radiotherapy, to make these kinds of cancer treatments more effective.

● Dr. Marianne Koritzinsky, Tier 1 Canada Research Chair in Cancer Redox and Radiation Biology (new). Dr. Koritzinksy is a Senior Scientist at UHN’s Princess Margaret Cancer Centre and a Professor in the Departments of Radiation Oncology and Medical Biophysics at U of T. The funding from this Chair will go toward improving cancer therapies by advancing research in redox homeostasis—the balance between oxidative and anti-oxidative molecules in a cell or tissue, which can be a key driver of cancer and a vulnerability for new targeted treatments.

● Dr. Tony Lam, Tier 1 Canada Research Chair in Diabetes and Obesity (renewal). Dr Lam is a Senior Scientist at UHN and a Professor in the Departments of Physiology and Medicine at U of T. He is also Associate Director, Research at the Banting and Best Diabetes Centre at U of T. His work aims to better understand the causes of obesity and diabetes by investigating how nutrients are sensed in the small intestine, kidney, and the brain.

The CRC Program is a national initiative designed to make Canada a global leader in research. Through this program, the federal government invests up to $311 million annually to support world-class researchers across disciplines, enhancing academic excellence, competitiveness, and the training of future skilled professionals.

See here for a full list of results and here for the press release.

Identifying Genetic Modifiers

Rare DNA changes may influence schizophrenia diagnosis in high-risk individuals.

Image Caption: Schizophrenia risk arises from multiple genetic factors, with one well-known risk factor being a deletion in a region of DNA called 22q11.2. However, no single genetic change can predict who will develop the disorder.

About one in four people with a rare genetic change called a 22q11.2 deletion will develop schizophrenia. A study co-led by UHN has uncovered new clues as to why some people with this high genetic risk go on to develop the condition while others do not.

Schizophrenia is a brain disorder that affects how people think and behave and requires lifelong treatment. While several genetic factors are linked to the illness, a missing portion of DNA in a region called 22q11.2 is one of the strongest known risk factors.

Despite this elevated risk, most people with the deletion do not develop schizophrenia. Therefore, these individuals represent a population that can help researchers understand what additional genetic factors may influence whether the condition develops.

Although schizophrenia is influenced by many different genes, none of the genetic changes identified alone can reliably predict who will get schizophrenia. There is evidence that tandem repeats—repeated stretches of DNA—can raise schizophrenia risk when they become unusually long. These repeats, called tandem repeat expansions (TREs), are like when a word in a sentence is accidentally copied many times. This extra repetition can make gene instructions harder for cells to read properly.

The team, co-led by Dr. Anne Bassett, UHN Senior Scientist, set out to test whether TREs could be a significant genetic modifier for schizophrenia in the presence of a high-risk 22q11.2 deletion. This analysis could also help in determining potential molecular mechanisms of disease and new treatment targets.

By analyzing the genomes of 438 unrelated people with this deletion, the team found that TREs were more common in those diagnosed with schizophrenia. These repeats were often located in DNA regions that help control how genes are expressed. Analysis further revealed that the affected genes are active in brain cells in the prefrontal cortex, an area linked to thinking and behaviour. Some of these genes, including DLGAP2 and DMPK, play key roles in brain development and communication between nerve cells.

These findings suggest that TREs may act as additional genetic risk factors, helping explain why schizophrenia develops in some high-risk individuals. They also provide more insight into how schizophrenia develops at the biological level and support the idea that genome sequencing could be used more widely to help detect complex diseases earlier.

Muyang Cheng is a Doctoral Candidate at The Hospital for Sick Children and the first author of the study.

Dr. Ryan Yuen is a Senior Scientist in Genetics & Genome Biology at The Hospital for Sick Children and an Associate Professor in the Department of Molecular Genetics at the University of Toronto. He is the co-corresponding author of the study.

Dr. Anne Bassett is a Senior Scientist at UHN and a Professor in the Department of Psychiatry at the University of Toronto. She is also the Director of the Clinical Genetics Research Program at the Centre for Addiction and Mental Health (CAMH). She is the co-corresponding author of the study.

This work was supported by the Canadian Institutes of Health Research, the National Institute of Mental Health, Brain Canada, the McLaughlin Centre at the University of Toronto Accelerator grants program, the Canada Research Chairs program, and the inaugural Dalglish Chair in 22q11.2 Deletion Syndrome at the University Health Network and University of Toronto to Dr. Bassett, administered through the UHN Foundation.

Cheng M, Yin Y, Engchuan W, Heung T; International 22q11.2 Brain Behavior Consortium (IBBC); Morrow BE, Bassett AS, Yuen RKC. Genome-wide tandem repeat expansions modify schizophrenia risk in the presence of a 22q11.2 deletion. Mol Psychiatry. 2026 Apr 15. doi: 10.1038/s41380-026-03574-8. Epub ahead of print.

Unravelling Myelin Stability

New lab model identifies how brain cells maintain myelin, and how breakdown may lead to MS.

Image Caption: Myelin is critical for efficient electrical signalling in the nervous system. When myelin is lost, like in multiple sclerosis (MS), neuron-to-neuron communication is disrupted, leading to symptoms such as muscle weakness, pain, and mood changes.

Oligodendrocytes—supportive cells in the brain and spinal cord (the central nervous system, or CNS)—play a critical role in maintaining myelin, the protective layer that surrounds nerve fibres. Loss or damage to myelin is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). 

“During myelin formation, oligodendrocytes use a process called vesicle trafficking to deliver materials needed to build the myelin layer in cellular packages,” said first author Chun Hin Chow. “It was not clear whether this same process continues to maintain myelin once formed.”

To address this gap, Dr. Shuzo Sugita and colleagues at UHN’s Krembil Brain Institute (KBI) identified a mechanism by which oligodendrocytes maintain myelin in the adult brain—and how disruption of this process may contribute to disease.

In a new study published in Nature Communications, the team developed an experimental model that enabled them to switch off a protein called SNAP-23 after myelin formation was complete. SNAP-23 is part of a group of proteins called SNAREs. These proteins allow vesicles—small membrane-bound packages that carry materials inside cells—to fuse with their target and release their contents.

When SNAP-23 was turned off, myelin broke down within a few weeks. The loss of myelin was accompanied by structural and functional changes in the CNS similar to those seen in diseases such as MS and Alzheimer disease. The researchers also observed a buildup of myelin-related proteins within oligodendrocytes, suggesting that other SNARE proteins may not compensate for the loss of SNAP-23.

Together, these findings suggest that vesicle trafficking is essential for maintaining myelin in adulthood, and that this process is SNAP-23 dependent.

The team also observed increased inflammation and immune cell activity in the CNS after SNAP-23 was disabled—another hallmark of demyelinating neurodegenerative diseases like MS. Compared with other models, the KBI team’s SNAP-23 model did not require external immune modification and produced an immune response soon after myelin loss, making it more representative of what happens in human neurodegenerative processes.

By uncovering how myelin maintenance breaks down, the study provides new insight into the early stages of diseases like MS. The results also highlight SNAP-23–dependent trafficking as a potential therapeutic target, offering a new strategy that could slow or prevent myelin loss at an early stage of disease.

Chun Hin Chow, Graduate Researcher at UHN’s Krembil Brain Institute and PhD candidate at the University of Toronto, is the first author of this study. 

Drs. Shuzo Sugita and Olga Rojas, Senior Scientist and Scientist, respectively, at UHN’s Krembil Brain Institute, are the senior and corresponding authors on this study. Drs. Sugita and Rojas are also a Professor of Physiologyu and an Assistant Professor of Immunology, respectively, at the University of Toronto’s Temerty Faculty of Medicine. 

This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Krembil Foundation, the University of Toronto, and UHN Foundation.  

Chow CH, Huang M, Regmi A, Rai J, Harada H, Eide S, Sun HS, Feng ZP, Monnier PP, Okamoto K, Zhang L, Rojas OL, Sugita S. SNAP-23 mediated vesicular trafficking in oligodendrocytes is necessary to maintain adult myelin integrity in mice. Nat Comms. 25 May 2026. DOI: 10.1038/s41467-026-73381-w. 

Brain Stimulation to Treat OCD

Large-scale UHN-led study finds brain stimulation treatments may help people with severe OCD.

Image Caption: Obsessive compulsive disorder (OCD) affects 2–3% of people globally, yet is one of the leading causes of disability from mental health conditions. The need for new treatments is critical, particularly for those with severe manifestations of the disorder.

A new study from UHN’s Krembil Brain Institute (KBI) suggests that brain stimulation treatments, also called neuromodulation, may offer new hope for individuals living with severe obsessive-compulsive disorder (OCD). The findings of this meta-analysis, which combines results from many studies, suggest brain stimulation may help people better manage symptoms and improve quality of life.

OCD is a mental health condition characterized by intrusive, distressing thoughts (obsessions) and repetitive behaviours (compulsions) performed to reduce anxiety. These symptoms can take a serious toll and impair daily life. For 30–40% of patients, standard treatments fail to provide relief, and some do not respond even to additional medications used when first-line treatments do not work. This severe form of treatment resistance is known as treatment-refractory OCD.

As researchers learn more about how different parts of the brain communicate in OCD, new treatments have emerged that aim to treat the brain networks directly. These therapies, called neuromodulation, use controlled electrical or magnetic stimulation to adjust activity in specific areas of the brain. Until now, no study has comprehensively compared different brain-stimulating approaches, limiting understanding of which option is most effective.

The KBI team analyzed 142 studies involving 2,960 patients across four approaches: deep-brain stimulation (DBS), lesion-based surgery, transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS). DBS and lesion-based surgery are invasive, while tDCS and TMS are non-invasive.

Results showed that all techniques reduced OCD symptoms. While invasive approaches showed the strongest effects, non-invasive modalities still produced moderate improvements and may be a more accessible option for those with less severe symptoms. Researchers suggest invasive techniques perform better because they can more reliably and precisely target key communication areas deep in the brain, known as hubs.

"Our analysis points to the importance of considering how brain regions are connected when determining whether a region is an ideal candidate for neuromodulation, rather than its location alone," says KBI Assistant Scientist and senior author of the study, Dr. Jürgen Germann.

For people living with OCD for whom standard treatments have failed, this meta-analysis represents a step towards better symptom management and reduced disability as a result. The findings support the use of neuromodulation for severe OCD while also shedding light on the underlying brain circuitry and potential therapeutic targets. Future research that continues to focus on how brain networks function could help make brain stimulation treatments for OCD more precise and personalized.

Dr. Flavia Venetucci Gouveia, Scientist at The Hospital for Sick Children and Assistant Professor in the Department of Medical Biophysics at the University of Toronto, is the first author of this study.

Dr. Jürgen Germann, Assistant Scientist at UHN’s Krembil Brain Institute and Assistant Professor at the University of Toronto’s Institute of Biomedical Engineering, is the senior author of this study.

This work was supported by the Canadian Institutes of Health Research, Brain Canada Foundation, the Shireen and Edna Marcus Foundation, and UHN Foundation.

Dr. Andres Lozano is a co-founder of Functional Neuromodulation and a consultant for Boston Scientific, Medtronic and Abbott.

Gouveia FV, Elias GJB, Wong EHY, Yang A, Beyn M, Mesich A, Omere U, Iskin SA, Bai Y, Hu CK, Boutet A, Lozano AM, Germann J. Neuromodulation for treatment-resistant obsessive–compulsive disorder: a systematic review, meta-analysis and network analysis. Nat Mental Health. 2026 Apr 13. DOI: 10.1038/s44220-026-00586-9.