Researchers at UHN are part of a team evaluating a potential new therapy for people with long-standing and hard-to-manage type 1 diabetes (T1D) who experience frequent, severe low blood sugar events. Results from an early-stage clinical trial, recently published in the New England Journal of Medicine, show promise for an approach to restore insulin production using stem cell–derived islets—clusters of cells in the pancreas that produce and secrete hormones.
More than 8 million people worldwide live with T1D, where the body's immune system destroys insulin-producing cells in the pancreas. Managing T1D remains difficult due to specific insulin therapy and glucose monitoring requirements. Even with the best tools, the disease can lead to serious long-term health complications.
A multi-site trial that includes UHN as one of the clinical sites has investigated a new therapy called zimislecel, which uses lab-grown insulin-producing islets derived from pluripotent stem cells—cells that can develop into any tissue type. These cells are infused into the liver through the portal vein, a blood vessel that carries blood from organs in the abdomen to the liver. Participants also received immunosuppressive medications to help prevent rejection of the transplanted cells.
Dr. Trevor Reichman, Surgical Director of the Pancreas and Islet Transplant Program at UHN’s Ajmera Transplant Centre and Clinician Investigator UHN, is the study’s lead Canadian author.
The study included 14 adults with longstanding T1D who had impaired ability to perceive the onset of hypoglycemia and recurrent severe hypoglycemia. Hypoglycemia occurs when blood sugar drops too low and can cause symptoms such as confusion, dizziness, seizures, or loss of consciousness. Severe cases require help from another person and can be life-threatening.
Before treatment, none of the participants produced measurable insulin on their own. One year after a single infusion of zimislecel, all participants who received the full dose experienced improved blood sugar control and no severe hypoglycemic events. Ten of these participants (83%) were insulin-independent at the one-year mark. Most reported side effects were mild or moderate and consistent with those seen in transplant recipients.
While these results are early and based on a small group, they suggest that stem cell–derived islets may help restore natural insulin production and improve safety for people with high-risk T1D. Ongoing studies will provide more insight into the long-term effectiveness, safety, and accessibility of this approach. The study is now in Phase 3, which will take the total participant number to 50.
UHN continues to play a key role in research that supports the safe and evidence-based advancement of new therapies for diabetes and other chronic diseases.
Dr. Trevor Reichman, Clinician Investigator at UHN and Associate Professor in the Department of Surgery at the University of Toronto, is the first author of this study that includes investigators in the VX-880-101 (zimislecel) FORWARD Study Group.
This study was funded by Vertex Pharmaceuticals and supported by UHN Foundation.
Reichman TW, Markmann JF, Odorico J, Witkowski P, Fung JJ, Wijkstrom M, Kandeel F, de Koning EJP, Peters AL, Mathieu C, Kean LS, Bruinsma BG, Wang C, Mascia M, Sanna B, Marigowda G, Pagliuca F, Melton D, Ricordi C, Rickels MR; VX-880-101 FORWARD Study Group. Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes. N Engl J Med. 2025 Jun 20. doi: 10.1056/NEJMoa2506549. Epub ahead of print. PMID: 40544428.
In neurodegenerative diseases (ND), such as Alzheimer disease or Amyotrophic Lateral Sclerosis (ALS), early diagnosis is critical for the most effective—or disease-modifying—treatments. Neuroinflammation, which is defined by increased levels of inflammation-causing proteins in the brain, is a key feature of these conditions.
Previous studies suggest neuroinflammation can be detected before other brain changes that are typically used to diagnose NDs appear. This means it could be a marker for earlier diagnosis. Unfortunately, many current diagnostic tools cannot detect signs of neuroinflammation—or they require invasive procedures.
A recent study from UHN’s Krembil Brain Institute (KBI) suggests free-water diffusion (FWD) MRI could fill this diagnostic gap. Free water is water in the brain that is not contained inside brain cells. FWD MRI measures how much of this water is present and how it moves. Changes in its amount, location, or movement can signal processes like neuroinflammation and cell death.
The KBI team analyzed MRI data and blood samples from 367 patients with various NDs collected through the Ontario Neurodegenerative Research Initiative (ONDRI) database. They assessed FWD patterns in brain scans and measured blood levels of two protein markers—GFAP (linked to neuroinflammation) and NfL (linked to cell damage).
Using machine learning, the researchers found that specific FWD patterns could predict GFAP levels, suggesting the technique may detect neuroinflammation. They also identified differences in FWD patterns between different NDs—hinting that FWD MRI could be used to help identify not only the presence of neuroinflammation but also the type of ND in its early stages.
“Further studies in larger and more diverse groups are needed to confirm reliability and effectiveness,” says the study’s senior author and a Krembil Clinician Investigator, Dr. Carmela Tartaglia. “But we believe FWD MRI has great potential as a diagnostic tool.”
As a non-invasive technique that uses existing technologies, FWD MRI offers a way to make ND diagnosis at an earlier stage easier and more widely available. For more patients, this could mean a better chance at effective management of and a life less impacted by neurodegeneration.
The first author of this study is Vishaal Sumra, a PhD candidate at the University of Toronto’s Institute of Medical Science.
The senior author is Dr. Carmela Tartaglia, a Clinician Investigator at UHN’s Krembil Brain Institute and a professor at the University of Toronto’s Tanz Centre for Neurodegenerative Diseases.
This work was supported by UHN Foundation. The ONDRI study was supported by the Ontario Brain Institute (OBI).
The authors report no competing interests for this work. For a full list of financial and personal interests, see the publication.
Sumra V, Hadian M, Dilliott AA, Farhan SMK, Frank AR, Lang AE, Roberts AC, Troyer A, Arnott SR, Marras C, Tang-Wai DF, Finger E, Rogaeva E, Orange JB, Ramirez J, Zinman L, Binns M, Borrie M, Freedman M, Ozzoude M, Bartha R, Swartz RH, Munoz D, Masellis M, Black SE, Dixon RA, Dowlatshahi D, Grimes D, Hassan A, Hegele RA, Kumar S, Pasternak S, Pollock B, Rajji T, Sahlas D, Saposnik G, Tartaglia MC; ONDRI Investigators. Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration. J Neurol. 2025 Jun 25;272(7):478. doi: 10.1007/s00415-025-13201-1.
Three UHN research teams have received a total of $1.2 million through the 2025 Canadian Cancer Society-UHN Research Grants on Neurofibromatosis and Cancer: Probing the Links. This grant was enabled through the generosity of the Elisabeth Raab Foundation.
This joint funding initiative—supported by the Canadian Cancer Society, UHN, and the Toronto Elisabeth Raab Accelerator of Science to End Neurofibromatosis (To-ERASEnf)—aims to advance the understanding and treatment of neurofibromatosis type 1 (NF1), a genetic disorder associated with an increased risk of cancer. The program fosters collaboration between cancer researchers and experts in NF1 and related fields to uncover the genomic and molecular drivers of cancer in NF1. This research is part of a growing field of investigation into the relationship between cancer and the nervous system.
The following three projects received funding:
Project Title: Understanding and improving health care for people with NF1
Lead Investigator: Dr. Carolina Barnett-Tapia, Clinician Scientist at UHN
Dr. Barnett-Tapia and her research team are examining cancer development patterns in individuals with NF1. Using data from a registry of over 2,000 patients with NF1, the research team will assess screening practices, cancer types, and patient outcomes. The findings will help inform testing guidelines to support early detection and improve care delivery.
Project Title: Finding new ways to treat nerve tumours
Lead Investigators: Dr. Dalia Barsyte-Lovejoy, Affiliate Scientist at UHN’s Princess Margaret Cancer Centre (PM), and Dr. Suganth Suppiah, Clinician Scientist at PM.
This project investigates why some nerve tumours in people with NF1 become cancerous. By studying and altering tumour cell pathways in the lab, the team will shed light on how these cancers develop and test new treatments that could prevent or stop tumour progression.
Project Title: Testing tumour immunotherapy in models of neurofibromatosis type 1
Lead Investigator: Dr. David Kirsch, Senior Scientist at PM.
Dr. Kirsch is exploring whether immunotherapy—a type of treatment that helps the immune system fight cancer—can be effective for people with NF1 who develop aggressive soft tissue tumours. Using experimental models, the research team will test immunotherapy alone and in combination with radiation to identify safer and more effective treatment options.
Congratulations to the awardees. Read more on the grants here.
Air pollution, generated from sources such as burning fossil fuels and wildfire smoke, is a leading environmental health threat worldwide. In a new study from UHN, researchers found that long-term exposure to air pollution is associated with myocardial fibrosis—scarring of heart muscle that can lead to poor outcomes for cardiovascular disease.
The majority of the global population lives in areas with air pollution levels exceeding World Health Organization air quality limits. Fine particulate matter with a 2.5-μm or smaller diameter (PM2.5) is the most thoroughly studied component of air pollution. These tiny airborne particles can be inhaled deep into the lungs and are associated with an increased risk of cardiovascular diseases such as heart attack and stroke. However, exactly how PM2.5 affects the heart’s structure and function remains unclear.
A team led by Dr. Kate Hanneman used cardiac MRI to non-invasively measure fibrosis in the heart muscle and determine its relationship to long-term exposure to PM2.5. They analyzed cardiac MRI scans from 694 patients, including 493 with dilated cardiomyopathy—a condition where the heart becomes enlarged and weakened—and 201 with healthy hearts.
The team measured diffuse myocardial fibrosis—when scar tissue abnormally accumulates throughout the heart muscle—using a specialized MRI technique called T1 mapping. They also calculated each person’s average daily PM2.5 exposure in the year preceding MRI imaging, based on air quality measurements near their homes.
Results showed a clear trend: for every small increase in PM2.5 levels, both patients with heart disease and healthy individuals had more heart muscle scarring. The effect was strongest in women, smokers, and people with high blood pressure.
These findings suggest that long-term air pollution exposure could damage heart tissue, potentially increasing the risk of future heart problems. With wildfires becoming more frequent, these results highlight the need for public health measures to reduce air pollution and for individuals to limit exposure whenever possible.
Dr. Jacques Du Plessis, who was a clinical cardiovascular imaging fellow at the University of Toronto, is the first author of the study.
Dr. Kate Hanneman, Clinician Scientist at UHN and Associate Professor in the Department of Medical Imaging at the University of Toronto, is the corresponding author of the study.
This work was supported by UHN Foundation.
Dr. Kate Hanneman has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi, and is an associate editor for Radiology and Radiology: Cardiothoracic Imaging. For a full list of competing interests, see the manuscript.
Du Plessis J, DesRoche C, Delaney S, Nethery RC, Hong R, Thavendiranathan P, Ross H, Castillo F, Hanneman K. Association between Long-term Exposure to Ambient Air Pollution and Myocardial Fibrosis Assessed with Cardiac MRI. Radiology. 2025 Jul;316(1):e250331. doi: 10.1148/radiol.250331.
Welcome to the latest issue of Research Spotlight.
As Canada’s largest research hospital, UHN is a national and international source for discovery, education, and patient care. This newsletter highlights top research advancements from over 5,000 members of TeamUHN—a diverse group of trainees, staff, and principal investigators who conduct research at UHN.
Stories in this month’s issue:
● Cell Lineage Linked to Leukemia Type: Study explores human blood cell development and why certain blood cancers can switch lineages.
● Precision Diagnosis for Liver Grafts: New AI tool helps identify liver graft injuries early, enabling faster treatment decisions.
● Better Recovery Starts in the Mind: Three studies examine how targeting mental health and cognition may improve surgical outcomes.
● Adapting Care for Complex Needs: Assessing the need for more flexible care systems to better support complex recovery.
Read these stories and more online here. To read previous issues, see the newsletter archive.
Researchers at the Princess Margaret Cancer Centre (PM) have developed a new AI tool to better understand how cells communicate with each other in diseases such as cancer.
Cells communicate to coordinate essential functions and build tissues. When this communication breaks down, it can contribute to diseases like cancer by promoting tumour-related inflammation, encouraging the growth of blood vessels, and triggering metastasis. Understanding how cells communicate during various cell and tissue functions may help researchers develop better treatments for cancer.
Detecting cell-to-cell communication at a large scale remains challenging. Current techniques use sequencing to identify pairs of molecules involved in communication. However, these techniques can mistakenly detect interactions, do not capture signals between individual cells, and only identify single pairs of interacting molecules, as opposed to complex networks composed of many interacting molecules across multiple cells.
To address these challenges, a team led by Dr. Gregory Schwartz, a Scientist at PM, developed Cell Neural Networks on Spatial Transcriptomics (CellNEST)—an AI-based tool that identifies complex cell-cell communication patterns between individual cells using advanced machine learning.
CellNEST can detect “relay-style” signalling, where messages pass through chains of cells via multiple molecular messengers called ligands and receptors.
To evaluate CellNest, the team applied the tool to five biological situations across different tissues, species, and technologies. They found that CellNEST outperformed existing techniques, consistently capturing known communication patterns in both healthy and diseased conditions, while also identifying new potential relay networks.
The method detected guiding signals in human lymph nodes, identified aggressive cancer communication in lung and colorectal tumours, and uncovered new patterns of communication in pancreatic cancer. Specifically, in a cohort of patients with pancreatic cancer, CellNEST revealed key cell–cell communication linked to disease progression, treatment response, and survival, and mapped these signals to known cancer subtypes.
CellNEST is also paired with a user-friendly online platform that allows scientists to explore these cellular conversations in real tissue samples. This innovation could open new avenues for understanding how diseases spread and for blocking harmful cellular interactions through targeted therapies.
CellNEST is available at https://github.com/schwartzlab-methods/CellNEST.
Dr. Fatema Tuz Zohora, a Postdoctoral Researcher at Princess Margaret Cancer Centre, is a co-first author of the study.
Deisha Paliwal, a Master's student at Princess Margaret Cancer Centre, is also a co-first author of the study.
Dr. Gregory Schwartz, a Scientist at Princess Margaret Cancer Centre and Assistant Professor in the Department of Medical Biophysics at the University of Toronto, is the corresponding author of the study.
This work was supported by The Princess Margaret Cancer Foundation, the Canadian Cancer Society, the Natural Sciences and Engineering Research Council of Canada, the Social Sciences and Humanities Research Council, the Canada Foundation for Innovation, the Ontario Institute for Cancer Research, the University of Toronto, the Government of Ontario, and Schmidt Sciences.
Dr. Gregory Schwartz is a Tier 2 Canada Research Chair in Bioinformatics and Computational Biology.
Zohora FT, Paliwal D, Flores-Figueroa E, Li J, Gao T, Notta F, Schwartz GW. CellNEST reveals cell-cell relay networks using attention mechanisms on spatial transcriptomics. Nat Methods. 2025 Jul;22(7):1505-1519. doi: 10.1038/s41592-025-02721-3. Epub 2025 Jun 6.
Listening while completing complex tasks—such as driving and talking with a passenger—can become more difficult with age due to gradual changes in hearing and cognition. Researchers from the KITE Research Institute (KITE) at UHN found that older adults experience more difficulty multitasking while driving than younger adults and identified strategies to help improve driving safety.
The study led by Katherine Bak, first author and PhD student in the lab of Dr. Jennifer Campos, analyzed the driving performance of 48 licensed drivers—including younger adults with an average age of 26 and older adults with an average age of 68. Using an advanced driving simulator located at the KITE DriverLab, participants navigated both simple rural roads and complex city environments while listening to phrases spoken with varying levels of background noise. Listening accuracy was measured by how well participants could repeat the phrases, while driving performance was assessed by tracking how well they maintained their lane position.
The results showed that older adults had poorer listening accuracy than younger adults, particularly when driving in city environments and under noisier conditions. Both age groups showed some decline in driving performance when listening and driving; however, older adults had more variability in their lane positioning.
These findings suggest that as people age, multitasking on the road becomes more mentally demanding. Everyday distractions—such as conversations, navigation systems, and background noise—may increase mental load and pose safety risks for older drivers.
Future work should explore how improving in-vehicle acoustics, reducing auditory distractions, or providing cognitive training could help reduce multitasking strain—supporting older adults in staying mobile, independent, and safe behind the wheel.
Katherine Bak, first author of the study, is a PhD student in the lab of Dr. Jennifer Campos.
Dr. Jennifer Campos, senior author of the study, is a Senior Scientist at the KITE Research Institute and the Associate Director of Academics at the Toronto Rehabilitation Institute. At the University of Toronto, she is a Professor at the Rehabilitation Sciences Institute and the Department of Psychology.
This work was supported by UHN Foundation and the Natural Sciences and Engineering Research Council of Canada. Dr. Campos also holds a Tier 2 Canada Research Chair in Multisensory Integration and Aging.
Bak K, Arnold K, Darakjian L, Pichora-Fuller MK, Russo FA, Campos JL. Dual-task costs of listening while driving in older and younger adults. PLoS One. 2025 May 29. doi: 10.1371/journal.pone.0324657.
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.
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