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.
A new study from researchers at UHN has found that activating a protein called Takeda G protein-coupled receptor 5 (TGR5) in a specific brain region—the nucleus of the solitary tract (NTS)—can reduce food intake and improve signalling pathways disrupted in obesity.
Eating increases the levels of bile acid in the blood. Bile acids are made in the liver from cholesterol and undergo several chemical changes, eventually aiding fat digestion, regulating cholesterol levels, and signalling through specific receptors (like TGR5) that influence metabolism. Parts of the brainstem—such as the NTS, which processes signals from internal organs, and the area postrema (AP), which detects hormones related to hunger and nausea—help regulate appetite. However, it is unclear whether bile acids activate TGR5 in these brain regions to regulate feeding.
Obesity is often linked to leptin resistance, a condition where the hormone leptin no longer signals the brain effectively to suppress appetite. While leptin action in the NTS is known to affect food intake, the underlying pathways are poorly understood.
Using lab models, a research team led by Dr. Tony Lam investigated the relationship between TGR5 and leptin, examining whether activating the TGR5 receptor in the NTS or AP could influence appetite and leptin sensitivity.
In collaboration with Dr. Allison Xu from the University of California, San Francisco, they found that stimulating TGR5 in the NTS lowered food intake without causing nausea. Additionally, activating TGR5 in the NTS enhanced the brain’s sensitivity to leptin by boosting a key leptin-related signalling pathway (leptin-STAT3).
Findings also revealed that in these models, a high-fat diet interfered with natural signals to TGR5 in the NTS that normally help control appetite. When they directly added this signal back into the brain, it improved leptin signalling and reduced appetite.
Overall, this study indicates that TGR5 in the NTS plays a key role in regulating food intake by enhancing leptin signalling. TGR5 could be a promising target for treating obesity by combating leptin resistance.
Kyla Bruce, Doctoral Candidate at the Institute of Medical Science at the University of Toronto and UHN, is co-first author of the study.
Dr. Song-Yang Zhang, former Postdoctoral Researcher at UHN and current Assistant Professor at McGill University, is co-first author of the study
Dr. Tony Lam, Senior Scientist at Toronto General Hospital Research Institute and Professor in the Department of Physiology and Medicine at the University of Toronto, is the corresponding author of the study.
This work was supported by the Canadian Institutes of Health Research, the Banting and Best Diabetes Centre, the Government of Ontario, the Joseph and Vera Long Foundation, and UHN Foundation.
Dr. Tony Lam is a Tier 1 Canada Research Chair in Obesity
Bruce K, Zhang SY, Garrido AN, Wang MT, Bachor TP, Wang P, Xu AW, Yang Z, Lam TKT. Pharmacological and physiological activation of TGR5 in the NTS lowers food intake by enhancing leptin-STAT3 signaling. Nat Commun. 2025 May 29. doi: 10.1038/s41467-025-60331-1.
The results of the Spring 2025 Canadian Institutes of Health Research (CIHR) Project Grant funding competition have been announced. The Project Grant program is designed to offer scientists, at any stage of their careers, funding for ideas with the greatest potential to advance health-related knowledge, research methodologies, patient care, and overall outcomes.
The results of this round of funding were significant—31 research teams at UHN were awarded more than $27 million through 26 full research grants and 5 priority announcement grants. Totalling $411 million, 435 full research grants were awarded across Canada. An additional investment of $5.1 million supported 46 priority announcement grants, and 9 supplemental prizes totalling $310,000 were also awarded.
Some of the funded projects from UHN researchers include:
● Dr. Gregory Schwartz, who is investigating ways to identify and target cell-to-cell communication in colorectal cancer
● Dr. Sowmya Viswanathan, along with Drs. Slava Epelman and Igor Jurisica, for a project exploring the role of immune cells in osteoarthritis
● Drs. Mamatha Bhat, Michael Brudno, and Divya Sharma, to develop DynaGraft—an AI tool designed to detect fibrosis in liver transplants
● Dr. Isaac Bogoch, for a public health-centric project that aims to reduce infections by analyzing patterns of pathogen spread
● Dr. James Shiraz Khan, with co-Principal Investigator Dr. Keyvan Karkouti, to explore the potential benefits of vitamin C before knee replacement surgery through clinical trials
Thanks in part to the generous support of the CIHR, UHN researchers are breaking barriers across the full spectrum of health research. From improving our understanding of cancer biology to creating wearable devices that can help detect heart failure remotely, UHN is proud to see its researchers’ dedication and contributions recognized on a national level. Congratulations to all the awardees for their continued contributions to advancing health research.
See the full list of winners here.
Clinicians often face difficult discussions about serious illness, prognosis, and care preferences, yet many lack formal training in the communication skills needed to navigate these conversations. This gap can lead to challenges in care delivery and clinical education. Researchers from The Institute for Education Research (TIER) at UHN explored how training clinicians in serious illness communication can build confidence in teaching and support a scalable approach to spreading these skills across health care teams.
Led by Dr. Warren Lewin, a TIER Clinician Investigator, the research team explored the experiences of 15 physicians and nurse practitioners from family medicine, palliative care, neurosurgery, internal medicine, and geriatrics as they completed an evidence-based course designed to help them learn and teach others to communicate effectively about serious illness.
Following the course, researchers administered surveys and interviews in which participants reported feeling more confident and comfortable both in having serious illness conversations and in teaching these skills. Many began using what they learned in their bedside teaching and clinical workshops. They valued the course’s structured approach and felt better equipped to teach serious illness communication skills and techniques. The course also fostered a sense of community across departments, laying the foundation for a shared teaching culture and continued skill development.
Participants noted that key supports—such as dedicated time for teaching, administrative assistance, access to ready-to-use teaching materials, and institutional support—are critical for applying the knowledge in clinical teaching and care settings.
These findings suggest that investing in clinician education can have a broad impact. As clinicians become more confident in teaching and using serious illness communication skills, patients and caregivers benefit from greater trust, reduced uncertainty, and more informed decision-making.
Dr. Helen James, first author of the study, was a former Palliative Medicine Clinical and Research Fellow at UHN.
At UHN, Dr. Warren Lewin, senior author of the study, is a Clinician Investigator at The Institute for Education Research, the Palliative Care Site Lead, and Director of The Conversation Lab at Toronto Western Hospital. He is also an Associate Professor in the Temerty Faculty of Medicine at the University of Toronto.
This work was supported by UHN Foundation.
James H., Forsey J., Albuquerque-Boutilier K., Gustin J., Lewin WH. An Educational Initiative Describing Clinician Teachers’ Experiences Following Serious Illness Communication Skills Faculty Development Training. Palliative Medicine Reports. 2025 May 26. DOI: 10.1089/pmr.2024.0073.
A research team at UHN is working to improve surgical outcomes for older adults by highlighting the specific needs and challenges of this group. In three recent studies, the team led by Dr. Frances Chung, a Clinician Investigator at Krembil Brain Institute (KBI), explored how preoperative attitudes, cognition, and mental health affect postoperative recovery.
Older adults—people aged 65 or older—undergo more surgical procedures than younger patients and experience higher rates of adverse outcomes. Previous studies have shown that preoperative factors such as mental health, cognitive function, and stress contribute to these outcomes.
Although the current standard of care includes some preoperative assessments, they often fail to fully capture the complex needs unique to older adults. Without an accurate understanding of these needs, appropriate improvements to care are unlikely, and adverse outcomes may persist.
To address this gap, Dr. Chung and her team conducted three studies in older adults undergoing non-cardiac surgery—two longitudinal, prospective studies and one single-time point, survey-based study:
● The first study used a 15-question survey in 307 patients to examine the role of depression.
● The second study assessed cognition in 394 patients using several short, clinically relevant cognitive tools, including the Montreal Cognitive Assessment (MoCA)—a 30-question assessment that can identify cognitive impairment.
● The third study surveyed 236 patients on five domains: surgery, anesthesia, functional disability, cognition, and finances.
Findings from the first two studies reinforced existing evidence linking mental and cognitive health to surgical outcomes. Notably, they revealed how many older adults are affected by depression and cognitive impairment. Preoperative depression affected 20% of participants, while cognitive impairment affected up to 35%. If left unaddressed, both conditions that may contribute to poor outcomes. Indeed, patients with cognitive impairment were found to have higher rates of adverse events such as emergency room visits 90-days post-surgery.
Despite the prevalence and clear impact of depression and cognitive impairment found in the first two studies, the third study found that many patients expressed limited concern about cognitive issues and showed low interest in preoperative assessments even though such screening before surgery could help guide care and prevent adverse outcomes.
Dr. Chung and her team’s research highlights the need to better align clinical care with patients’ needs and values. Improving patient education about the benefits of these interventions is critical. Without patient buy-in, even enhanced care standards may not improve outcomes.
Incorporating assessments for mental health and cognition into standard care offers a chance to intervene early and prevent complications. As the older adult population grows in Canada and beyond, reducing adverse outcomes may improve quality of life and reduce pressure on the health care system.
The first author of the study assessing depression, published in the British Journal of Anaesthesia, is Yasmin Alhamdah, a medical student at St. George’s University and a former master’s student in Dr. Chung’s lab.
The first author of the study assessing preoperative concerns and prehabilitation, published in the Journal of Clinical Anesthesia, is Melanie Li, a medical student at the University of Toronto.
The first author of the study assessing the role of cognitive impairment—presented as an abstract at the 2025 IARS & SOCCA Annual Meeting—is Ellene Yan, a PhD candidate at the Institute of Medical Sciences at the University of Toronto.
The senior author of all three publications is Dr. Frances Chung, a Krembil Clinician Investigator with the Krembil Brain Institute, ResMed Chair in Anesthesia, Sleep and Perioperative Medicine Research at UHN, and a Professor in the Department of Anesthesiology and Pain Medicine in the Temerty Faculty of Medicine at the University of Toronto.
This work was supported by the Ontario Long-Term Care Innovation Fund, the ResMed Foundation, Canadian Institutes of Health Research, and UHN Foundation.
For a complete list of competing interests, see the publications.
Alhamdah Y, Yan E, Butris N, Kapoor P, Lovblom LE, Rajji TK, Fischer CE, Mah L, Wong J, Islam S, Saripella A, He D, Chung F. Depression in older surgical patients: a multicentre prospective longitudinal study. Br J Anaesth. 2025 May 21. doi: 10.1016/j.bja.2025.04.016.
Li M, Yan E, Saripella A, Alhamdah Y, Nabipoor M, Alibhai SMH, Wong J, Chung F. Understanding preoperative concerns and attitudes towards prehabilitation in older surgical populations: A survey study. J Clin Anesth. 2025 Jun 5. doi: 10.1016/j.jclinane.2025.111895.
Yan E, Alhamdah Y, He D, Lovblom LE, Campbell S, Wong J, Chung F. Is poor performance on ultra-rapid cognitive screening tools associated with clinical outcomes? Findings from the Detection of Cognitive Impairment (Detect CI) study. Abstract presented at: 2025 Annual Meeting. 14th Annual Meeting of the International Anesthesia Research Society (IARS) & Society of Critical Care Anesthesiologists (SOCCA); 2025 Mar 20-23; Honolulu, Hawaii, USA.
A list of other publications from Dr. Chung’s group can be found here.
Researchers from UHN’s Princess Margaret Cancer Centre have demonstrated how specific cancer cells in a tumour are responsible for driving its growth and spread (also known as cancer propagation).
Despite advances in molecular profiling of cancer cells, disease progression and treatment resistance remain major challenges. This is due in part to the ability of cancer cell clones—groups of cancer cells derived from a single cell—to change their identity and behaviour, a phenomenon known as plasticity.
Scientists have long known that not every cell in a tumour has the ability to regrow the cancer. Only a small number of special cells—called clonogenic cells—can actually start new tumours and keep the cancer going. To cure the disease, these cells must be eliminated. In solid tumours (like breast or lung cancer), finding and studying these key cells has been difficult because they do not have clear markers.
In this study, researchers used a new technique involving genetic barcodes—unique DNA tags that allow scientists to track the descendants of individual cancer cells. Using this method along with advanced single-cell sequencing techniques, they studied over 20,000 individual breast cancer cell clones from 26 patient-derived breast cancer laboratory models.
By tracking these barcoded cells as they divided, the team discovered that fewer than 0.01% of clones were able to regrow tumours. These rare clones divided rapidly and expanded to become the dominant cell type. These clones were also able to reproduce the full gene expression profile of the original cancer model, indicating their ability to drive tumour growth.
In models of basal breast cancer—an aggressive subtype—the tumour-propagating clones showed high plasticity, changing their function and gene activity. The team also identified two distinct cell populations with different clonal growth behaviours and biological features. These results show that propagating clones have the ability to evolve, adapt, and grow into dominant clones that eventually become the majority, all originating from a single barcoded cell.
These findings deepen our understanding of how cancers evolve and resist treatment. This work could lead to therapies that better target these tumour-driving clones, with the approach used here potentially applicable to other solid cancers.
Dr. Long Nguyen, Scientist at Princess Margaret Cancer Centre and Assistant Professor in the Department of Medicine and Medical Biophysics at the University of Toronto, is the first and lead corresponding author of the study.
Dr. Carlos Caldas, Professor of Cancer Medicine at the University of Cambridge, is the co-corresponding author of the study.
This work would not have been possible without the generosity of all the patients who donated samples for the development of breast cancer laboratory models.
This work was supported by The Princess Margaret Cancer Foundation, the Hold’em for Life Early Career Professorship in Cancer Research from the Temerty Faculty of Medicine at the University of Toronto, the European Society For Medical Oncology, Conquer Cancer, The ASCO Foundation, the J.P. Bickell Foundation, the Marathon of Hope Cancer Centres Network, Cancer Research UK, UK Research and Innovation, the National Institute for Health and Care Research, European Research Council, and the Cambridge Commonwealth, European and International Trust.
Dr. Carlos Caldas received research grants (administered by the University of Cambridge) from Genentech, Roche, AstraZeneca, and Servier.
Nguyen LV, Eyal-Lubling Y, Guerrero-Romero D, Kronheim S, Chin SF, Manzano Garcia R, Sammut SJ, Lerda G, Lui AJW, Bardwell HA, Greenwood W, Shin HJ, Masina R, Kania K, Bruna A, Esmaeilishirazifard E, Kolyvas EA, Aparicio S, Rueda OM, Caldas C. Fitness and transcriptional plasticity of human breast cancer single-cell-derived clones. Cell Rep. 2025 May 27;44(5):115699. doi: 10.1016/j.celrep.2025.115699. Epub 2025 May 12.
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