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.
In the operating room, a removed tumour can look deceptively uniform — like any other piece of tissue. But within it lies a bustling city of cancer cells, blood vessels, and connective tissue, invisible to the naked eye. Dr. Ralph DaCosta’s research team at UHN’s Princess Margaret Cancer Centre turns this hidden world into vivid colour, revealing cancer’s behaviour in real time.
His team discovered a dynamic, constantly changing tumour microenvironment surrounding pancreatic cancer cells (published in Science Advances), that could help oncologists tailor treatment schedules for patients who have one of Canada’s deadliest cancers.
"We saw pockets of pancreatic cancer cells that are inherently hypoxic — in other words, they have low oxygen levels. They are enveloped by very dense layers of connective tissue called collagen fibers, preventing blood vessels from getting inside,” Ralph describes.
To detect pockets of oxygen-starved (hypoxic) cancer cells, the team, led by former doctoral student Dr. Timothy Samuel, used a sophisticated combination of fluorescent labelling and advanced optical microscopy in living models of cancer to light up different components in the tumour microenvironment.
Cancer cells in preclinical models were engineered to glow red (DsRed) at all times, while a built-in hypoxia sensor made them glow green (GFP) only under low-oxygen conditions. Blood vessels were highlighted in cyan using a fluorescent antibody, allowing the team to measure oxygen access relative to blood supply. Meanwhile, collagen fibers—key components of the tumour’s stiff, fibrotic structure—were visualized using second harmonic generation microscopy, a special form of laser light that makes collagen fibers shine like white snow under a spotlight.
These rigid, oxygen-starved pockets of cancer emerge, persist, and can contribute to tumour progression: they may fuel a vicious cycle of tumour growth and spread by cutting off oxygen, reshaping collagen and the microenvironment over time, and helping cancer cells evade treatment.
In a follow-up study published in Scientific Reports, the team used this imaging platform to track how patient pancreatic tumour cells responded to radiation. After radiation treatment, fewer cells continued to glow red, indicating reduced viability of cancer cells, and there was a reduction in green fluorescence, signalling less hypoxia. The presence of DNA damage markers and slowed cell growth confirmed that the treatment was effective. Through quantitative analysis, the study also offered insights into optimizing treatment timing and dosing to improve treatment outcomes.
This imaging system gained widespread recognition that led to a collaboration with Drs. Mark Minden, John Dick, Stephanie Xie, and Tak Mak (and collaborators abroad), to illuminate how blood cancers interact with the immune system and respond to immunotherapy. This time, the team needed ways to visualize whether cancer cells were alive or dead to better track treatment response, as the bone marrow microenvironment is remodelled during disease progression. They developed a new marker for tumour cell death — a pink fluorescent signal that is emitted when the treatment kills a leukemia cell.
“We have also found ways to visualize different immune cell populations in the bone marrow where leukemia cells develop,” Ralph adds. “It will let us see an entirely different cellular landscape with complex microarchitecture, and the interaction between leukemia cells and immune cells. I’m very excited by this new frontier where imaging can play a key role in improving our understanding of tumour biology. This type of work has never been done before.”
Ralph’s obsession with the optical world started when he was a child, building a ruby crystal laser in his garage. The resulting laser beam was invisible — until he sprinkled talcum powder in the air and saw it glow red. For the first time, he felt the magic of visualizing the unseeable. That moment inspired him to learn more about light through physics and math.
From a summer job in Dr. Brian Wilson’s Lab at the Princess Margaret Cancer Centre, he redirected his path to cancer research.
“I came upon a newspaper article that stated how a star scientist, Dr. Brian Wilson, was coming from Hamilton to Toronto to start a whole new field of bio-photonics.” Ralph cold-called Brian to express his interest in studying light for medical applications, which led to his first job and eventually a PhD. In 2014, Ralph started his own independent research lab and became a colleague alongside his mentor.
From tinkering with a simple laser device in his garage, Ralph went on to design advanced optical tools for medicine, including confocal microscopes that reveal details in tissue and cell biopsies, and fluorescence-based endoscopes now used in clinics to help detect early cancers and guide surgeries with greater precision.
“It was also mind-blowing to me that the curious kid with a garage-built laser is now solving clinical problems that can affect people around the globe.”
One of his early projects in Brian’s Lab was to detect precancerous lesions in the gastrointestinal tract that could lead to colon cancer. Ralph built an imaging device using blue light to excite molecules inside cancerous tissues that would give off signals for flat adenomas, dangerous precursor lesions that are near impossible to detect by the unaided eye of the clinician.
“If there was a sign of colon cancer, it would light up green, but all I saw was red,” Ralph recalled one particularly serendipitous night when he was examining one tissue sample in the lab.
The red signal turned out to be bacteria, not cancer-related, which unleashed a whole new field of application for the use of fluorescence light imaging technology in wound care. Bacterial hotspots are known to delay wound healing and lead to infection. Ralph modified the technology into a novel handheld device to detect elevated bacteria levels and provide real-time wound care monitoring and treatment guidance. Based on this innovative research, he founded MolecuLight Inc. in 2012, to commercialize the patented product and help patients globally through its Toronto and U.S. offices, for which he was awarded UHN Inventor of the Year in 2013. For more information, Ralph shared his innovation journey on the Behind the Breakthrough Podcast.
Ralph’s curiosity extends far beyond the cancer research laboratory. He is an avid gardener who conducts botany experiments on his kitchen table to investigate how different plants can talk to each other at night, examining leaves under fluorescence light. He is also a fisherman who ties and tests his own flies.
“Many things that inspire me are not directly related to cancer,” says Ralph. “If you look at other systems in the world, biological or non-biological, it can teach you a wide range of different things.”
Ralph excels in drawing analogies from one field and applying them in a different place. He also encourages his students to “look beyond the desk” to broaden their perspective, avoid tunnel vision, and inform scientific thinking.
“I want my two young daughters to also become people who have this ability to look at something completely unrelated to their profession, and look at it from different perspectives to extract the information that matters to them,” says Ralph. “That is the art of discovery.”
Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.
Hosted by UHN’s Princess Margaret Cancer Centre (PM), the Allan Slaight Breakthrough Forum marked the first-ever C8 Symposium, uniting top cancer researchers from eight premier global cancer research institutes.
Held on September 15 and 16, 2025, at the MaRS Auditorium in Toronto, the C8 Symposium brought together leading scientists from cancer research institutions across Canada, Australia, France, Israel, Japan, the UK, and the USA. The event was made possible by the generous support of La Fondation Emmanuelle Gattuso and The Slaight Family Foundation through the Allan Slaight Breakthrough Fund.
The two-day symposium featured over 30 expert talks, moderated discussions, poster presentations, and networking sessions focused on cutting-edge topics such as chemotherapy resistance, synthetic lethality—a treatment approach that targets specific lethal mutations in cancer cells, novel therapeutic targets, and tumour microenvironment dynamics.
The sessions were led by internationally renowned researchers including Drs. Aaron Schimmer and Brad Wouters (PM), Dr. Ricky Johnstone (Peter MacCallum Cancer Centre), Dr. Robert Bristow (Manchester Cancer Research Centre), Dr. Kevin Haigis (Dana-Farber Cancer Institute), Dr. Shai Izraeli (Tel Aviv University), Dr. Steven Le Gouill (Institut Curie), and Dr. Wakako Toga (National Cancer Center Japan).
Opening remarks from Dr. Schimmer, Senior Scientist and Director of PM, set the tone for the symposium, emphasizing the importance of global collaboration in tackling the complexity of cancer. Throughout the event, speakers shared insights into newly discovered cancer-driving mechanisms, innovative therapeutic strategies, emerging technologies, and translational research platforms aimed at improving patient outcomes.
(Pictured from left to right) Panel discussion with Dr. Hiroyuki Mano, Dr. Steven Le Gouill, and Dr. Marianne Koritzinsky, moderated by Dr. Brad Wouters.
A highlight of the symposium was a panel discussion on accelerating cancer target discovery and drug development, inspired by Dr. Hiroyuki Mano’s (National Cancer Center, Japan) presentation on a novel model that has transformed cancer drug discovery. The session featured Dr. Marianne Koritzinsky (PM), who introduced a promising new protein target for cancer, and Dr. Le Gouill, who shared insights into targeted therapy in Mantle Cell Lymphoma, emphasizing biology-driven treatment design.
“We are excited about the potential of collaborating at the institutional level to tackle the biggest problems and biggest opportunities in cancer,” said Dr. Wouters, PM Senior Scientist and Executive Vice President of Science and Research at UHN. “By aligning our institutional strengths, we can create environments that foster innovation, streamline discovery, and deliver impact at scale.”
The symposium also featured a poster session designed to spotlight the work of postdoctoral and emerging researchers, providing a valuable platform for the next generation of cancer scientists to showcase their research to an international audience.
The symposium concluded with a Leadership Summit focused on strategic planning for future C8 initiatives, including mentorship, capacity-building, and global alignment of comprehensive cancer centres. Discussions led by institutional leaders explored ways to support the cancer research workforce and foster international team science.
“This inaugural C8 Symposium marks a pivotal moment in global cancer collaboration,” said Dr. Schimmer. “By bringing together diverse expertise and perspectives, we are laying the foundation for transformative research that will shape the future of cancer care.”
Participants from the Allan Slaight Breakthrough Forum: Inaugural C8 Symposium
Research at UHN takes place across its research institutes, clinical programs, and collaborative centres. Each of these has specific areas of focus in human health and disease, and work together to advance shared areas of research interest. UHN's research spans the full breadth of the research pipeline, including basic, translational, clinical, policy, and education.
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