Researchers at UHN reveal how a molecule known as circular RNA (circRNA) drives the transformation of specific prostate and lung cancers into more aggressive, treatment-resistant forms, highlighting new potential therapeutic targets.
Prostate and lung adenocarcinomas are cancers that form in glands that line these organs. Interference of gene regulatory programs in neurons can transform these cancers into more aggressive types: neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC), respectively. Both NEPC and SCLC are neuroendocrine tumours, forming from neuroendocrine cells—nerve cells that also produce hormones. NEPC and SCLC are more difficult to treat and share similar genetic changes.
CircRNAs are a form of RNA, genetic material that generally does not produce proteins but instead helps regulate gene activity. Previous evidence has identified a link between circRNAs and the regulation of various biological processes important for cancer development. However, their role in driving cancer transformation remains unexplored.
Through gene expression analysis, a research team from the Princess Margaret Cancer Centre identified a specific circRNA, circRMST, which is highly active in NEPC and SCLC. They found that circRMST is essential for tumour growth and the expression of ASCL1—a key regulator for turning a cell into a neuroendocrine cell.
Using genetic tools in experimental models, the research team found that circRMST is also essential for the transformation of adenocarcinoma into aggressive neuroendocrine tumour types. Further analysis revealed that circRMST interacts with two other key proteins, SOX2 and NKX2-1, to promote ASCL1 expression and drive the development of neuroendocrine cell characteristics.
This research underscores the direct regulatory role of circRMST in the progression of prostate and lung adenocarcinoma. By highlighting an essential player in the changes of these cancers, the findings reveal potential new insights into therapeutic strategies for targeting neuroendocrine tumours.
Dr. Mona Teng, a former doctoral student at Princess Margaret Cancer Centre (PM) is the co-first author of the study.
Jiacheng Guo from the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China, is the co-first author of the study.
Dr. Xin Xu, a Postdoctoral Researcher at PM, is the co-first author of the study.
Dr. Housheng (Hansen) He, a Senior Scientist at PM, and Professor in the Department of Medical Biophysics at the University of Toronto is the lead corresponding author of the study.
Dr. Himisha Beltran, Associate Professor of Medicine at Dana Farber Cancer Institute and Harvard Medical School is a co-corresponding author of the study.
Dr. Jun Quin, Professor and Principal Investigator at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, is a co-corresponding author of the study.
This work was supported by the Canadian Institutes of Health Research, the Terry Fox Research Institute, the Marathon of Hope Cancer Centres Network, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer at Princess Margaret Cancer Centre, the Canada Foundation for Innovation, Cancer Research Society, National Institutes of Health/National Cancer Institute, the Clinical and Translational Science Center at Weill Cornell Medical Center, National Natural Science Foundation of China, Prostate Cancer Foundation (PCF) and the United States Department of Defense.
Dr. Housheng (Hansen) He is a Tier 1 Canada Research Chair in RNA Medicine.
Co-author Dr. Benjamin Lok reports grants from Pfizer; and grants, personal fees, and non-financial support from AstraZeneca outside the submitted work.
Teng M, Guo J, Xu X, Ci X, Mo Y, Kohen Y, Ni Z, Chen S, Guo WY, Bakht M, Ku S, Sigouros M, Luo W, Macarios CM, Xia Z, Chen M, Ul Haq S, Yang W, Berlin A, van der Kwast T, Ellis L, Zoubeidi A, Zheng G, Ming J, Wang Y, Cui H, Lok BH, Raught B, Beltran H, Qin J, He HH. Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation. Cancer Cell. 2025 May 12. doi: 10.1016/j.ccell.2025.03.027. Epub 2025 Apr 17.
For Dr. Lisa Boivin, a member of the Deninu Kųę́ First Nation in Denendeh (Northwest Territories) and an Indigenous Educator, making art is more than an act of creative expression. It is a chance to share knowledge in the way her ancestors have for centuries and help people understand the importance of cultural safety and Indigenous Peoples’ experiences in health care and research.
On Wednesday, May 28, members of the UHN community gathered in the De Gasperis Conservatory at Toronto General Hospital for an Arts-Based Education Open House to learn more about how Lisa educates through art. The afternoon promised a taste of the workshops Lisa hosts for UHN and Indigenous Peoples in the city.
Participants were encouraged to create their own artwork, leave their mark in the guestbook, and add to a large group collage. The space was filled with laughter, thoughtful conversations, and moments of connection as people explored their creativity together. Lisa shared the meanings behind the animals in the collage, explaining the important lessons they carry in Indigenous knowledge.
Throughout the afternoon, laughter and thoughtful conversation filled the air as participants’ creativity flourished, and Lisa shared Indigenous teachings on what people can learn from the various animals that were included in the collage.
Several of Lisa’s artworks were also on display at the event, including a print of her work entitled Unravelling the Whispers of Ancestors, which was raffled to one lucky attendee. Other winners took home copies of Lisa’s books: I Will See You Again and I Dream Medicine Dreams.
Events like this Open House bring the UHN community one step closer to decolonizing research and health care spaces. Centering the voices, teachings, and experiences of Indigenous communities is the first step toward ensuring research at UHN reflects their needs, but it is certainly not the last. With the help of incredible members of the community like Dr. Lisa Boivin, UHN is committed to the continued learning and work necessary to make UHN spaces safe for and welcoming to Indigenous Peoples.
The UHN community thanks all those who helped make this event such a success, including the UHN Research IDEA team.
To learn more about Lisa and her work, read her You @TeamUHN feature here.
To find out more about or book one of Lisa’s workshops, email Lisa at lisa.boivin@uhn.ca.
A new study from UHN shows how chronic liver inflammation alters the liver’s immune cells, making it more vulnerable to damage and influencing disease progression.
Chronic liver disease (CLD), including chronic hepatitis B, causes ongoing inflammation and leads to over two million deaths each year from cirrhosis (liver scarring) and a form of liver cancer called hepatocellular carcinoma.
Liver damage triggers changes in immune cells called macrophages—activating and recruiting them, as well as altering their composition. Macrophages normally protect the liver against damage. They originate from the embryo or from monocytes—white blood cells that are recruited after injury or infection.
In short-term infections, an influx of macrophages derived from monocytes helps clear out disease-causing microbes. However, in chronic infections, these same cells can fuel inflammation. Replacing the liver’s original macrophages with monocyte-derived ones may drive disease progression.
Studying this process is challenging because it is difficult to collect tissue samples over time during specific periods of inflammation. The research team, led by Dr. Adam Gehring, Senior Scientist at Toronto General Hospital Research Institute, overcame this by studying patients with chronic hepatitis B starting antiviral treatment.
Liver inflammation usually drops within six months of starting antiviral treatment. By taking small liver samples over time and using advanced single-cell analysis, scientists tracked immune changes during treatment. Even though inflammation and viral levels decreased, some immune cells remained altered—an unexpected finding.
They identified a unique group of monocyte-derived macrophages—called “inflammatory macrophages” or iMacs—found only in inflamed livers. These iMacs had a strong pro-inflammatory gene signature and remained altered even four years after treatment.
These findings suggest that inflammation and changes in macrophages are not transient and can have long-term effects—possibly pushing chronic liver disease toward cirrhosis or altering how patients respond to immunotherapy. Learning how iMacs form could help improve treatments for chronic liver disease and refine approaches for immunotherapy.
Dr. Juan Diego Sanchez Vasquez, Postdoctoral Researcher at UHN, is the first author of the study.
Dr. Adam Gehring, Senior Scientist at Toronto General Hospital Research Institute and Associate Professor in the Department of Immunology, is the senior author of the study.
This work was supported by the Canadian Institutes of Health Research, Gilead Sciences, and UHN Foundation.
Dr. Adam Gehring receives research funding from Aligos Therapeutics, Bluejay Therapeutics, GSK, Roche, Vir Biotechnology, and EVOQ Therapeutics and reports compensation from consulting and scientific advising for Aligos Therapeutics, Arbutus Biopharma, Assembly Biosciences, Bluejay Therapeutics, Gilead Sciences, GSK, Roche, Vir Biotechnology, and Virion Therapeutics.
See the manuscript for more competing interests.
Sanchez Vasquez JD, Nkongolo S, Traum D, Sotov V, Kim SC, Mahamed D, Mehrotra A, Patel A, Chen DY, Fung S, Gaggar A, Feld JJ, Chang KM, Wallin JJ, Wang BX, Janssen H, Gehring AJ. Virus-associated inflammation imprints an inflammatory profile on monocyte-derived macrophages in the human liver. J Clin Invest. 2025 Apr 15;135(8):e175241. doi: 10.1172/JCI175241.
The third annual International Conference on Aging, Innovation, and Rehabilitation (ICAIR), hosted by UHN’s KITE Research Institute, took place on May 1 and 2, 2025 at The Carlu in downtown Toronto.
The conference highlighted the latest innovations in aging and rehabilitation technology, showcasing advancements designed to improve the lives of individuals living with disabilities, injuries, and the effects of aging. This year’s event welcomed 500 attendees from around the world, fostering cross-disciplinary collaboration and the exchange of research and academic insights.
Keynote speakers delivered engaging and thought-provoking presentations that explored the future of technology, health care, and social impact. Featured speakers included the following:
● Dr. Helen Papagiannis, globally recognized expert on immersive technologies and bestselling author of Augmented Human: How Technology is Shaping the New Reality.
● Dr. Chet Moritz, Professor and Co-Director for the Center for Neurotechnology at the University of Washington.
● Dr. Andrew Boozary, Clinician Investigator at the Toronto General Hospital Research Institute, primary care physician, and founding executive director of the Gattuso Centre for Social Medicine at UHN.
The program also featured notable events, including the KITE Power Play Pitch Competition, the Three-Minute Talk (3MT) Competition, and the ICAIR Scientific Spotlight Series. These sessions provided a platform for emerging researchers and innovators to present their work and engage with peers across disciplines.
Learn more about the competitions and their winners here.
For thousands of liver transplant recipients worldwide, routine follow-up can quickly turn uncertain when liver enzyme levels rise—an early signal of potential graft injury. The diagnostic gold standard, a liver biopsy, is invasive and often delayed. Additionally, physicians may adjust management and immunosuppression based on intuition, sometimes before receiving biopsy results, which can lead to complications. A new AI-driven tool called GraftIQ provides a safer approach to the early management of patients with elevated liver enzymes.
Developed at the University Health Network (UHN), GraftIQ is a first-of-its-kind hybrid model that blends clinician expertise with machine learning to provide a multi-class prediction, meaning it can distinguish between several causes of liver graft injury. This “human-in-the-loop” approach enables the system to learn from both data and domain knowledge, thereby enhancing its ability to detect six major causes of graft injury.
Trained and validated on more than 8,000 biopsies across three continents, GraftIQ consistently outperformed traditional models, showing strong generalizability and clinical relevance. In trials, it helped identify conditions like acute cellular rejection, biliary obstruction, and recurrent hepatitis C with high accuracy—without the need for invasive testing.
Importantly, international partners collaborated on the external validation, including Drs. Joseph Ahn (Mayo Clinic, USA), Richard Taubert (Hannover Medical School, Germany), and Eunice Tan (National University Health System, Singapore). GraftIQ performed strongly in these validations, demonstrating a level of generalizability across three continents that is rare for health care AI tools.
“This kind of technology does not replace clinical judgment—it enhances it,” says Dr. Mamatha Bhat, Hepatologist and Co-Lead of the Transplant AI initiative and Scientist at UHN, who envisioned and led this project. “GraftIQ is a step toward faster diagnosis and more timely treatment decisions.”
By integrating seamlessly into clinical workflows, GraftIQ represents a scalable, multi-class decision-support tool for transplant programs worldwide. Its success underscores the value of global collaboration in evaluating health care AI tools. UHN stands at the forefront of applying responsible AI in medicine.
Dr. Divya Sharma, Senior Biostatistician at Princess Margaret Cancer Centre, and Assistant Professor in the Department of Mathematics and Statistics at York University, is co-first author of the study.
Dr. Neta Gotlieb, from the Department of Medicine at the University of Ottawa and Dr. Daljeet Chahal, from the Vancouver General Hospital, are co-first authors of the study.
Dr. Wei Xu, Clinician Scientist at the Princess Margaret Cancer Centre, and Professor at the Dalla Lana School of Public Health at the University of Toronto, is co-senior author of the study.
Dr. Mamatha Bhat, Clinician-Scientist and Hepatologist at Ajmera Transplant Centre, Scientist at the Toronto General Hospital Research Institute (TGHRI), and Associate Professor in the Department of Medicine at the University of Toronto, is co-senior author of the study.
This work was supported by grants to UHN investigators from the Canadian Society of Transplantation, the American Society of Transplantation (AST), the Canadian Institutes of Health Research (CIHR), and UHN Foundation.
Sharma D, Gotlieb N, Chahal D, Ahn JC, Engel B, Taubert R, Tan E, Yun LK, Naimimohasses S, Ray A, Han Y, Gehlaut S, Shojaee M, Sivanendran S, Naghibzadeh M, Azhie A, Keshavarzi S, Duan K, Lilly L, Selzner N, Tsien C, Jaeckel E, Xu W, Bhat M. GraftIQ: Hybrid multi-class neural network integrating clinical insight for multi-outcome prediction in liver transplant recipients. Nat Commun. 2025 May 28;16(1):4943. doi: 10.1038/s41467-025-59610-8. PMID: 40436838.
The UHN community mourns the loss of Dr. James Till, whose impactful research demonstrated the existence of stem cells, fundamentally transforming the future of medical science.
Born and raised on a farm in Lloydminster, Alberta, Dr. Till pursued his passion for science at the University of Saskatchewan, earning a B.Sc. in 1952 and an M.Sc. in physics in 1954. He then obtained a Ph.D. in biophysics from Yale University in 1957. Shortly thereafter, he was recruited to the Ontario Cancer Institute, now known as the Princess Margaret Cancer Centre (PM) at UHN.
At the Ontario Cancer Institute, Dr. Till collaborated with Dr. Ernest McCulloch, forming a partnership that would revolutionize biology. In 1961, through experiments involving the injection of bone marrow cells into irradiated experimental models, they provided the first description of blood-forming stem cells. Their 1963 publication in Nature further demonstrated that each spleen colony generated from these experiments originated from a single cell, offering the first functional definition of stem cells. Collaborating with Dr. Lou Siminovitch, they further showed that these marrow cells possessed the capacity for self-renewal.
Dr. Till continued to advance stem cell research for over 15 years, exploring the potential of stem cells to differentiate into various cell types and the feasibility of isolating viable stem cells.
The impact of this work has been profound, laying the groundwork for bone marrow transplants and forming the basis for numerous stem cell therapies and regenerative medicine approaches aimed at repairing or regenerating damaged tissues and organs.
In the 1980s, Dr. Till expanded his research interests to encompass various aspects of cancer care, including quality of life, research ethics, and the decision-making capacities of cancer patients. He also explored the role of the Internet as a source of information, support, and advocacy, and examined the impact of this information on patient care.
Dr. Till served as a Professor Emeritus at the University of Toronto. His numerous accolades include the Canada Gairdner International Award in 1969, appointment as an Officer of the Order of Canada in 1994, election as a Fellow of the Royal Society in 2000, and induction into the Canadian Medical Hall of Fame in 2004.
Dr. Till’s legacy endures through the transformative research he inspired and the many scientists he mentored, whose work continues to advance stem cell science and improve lives worldwide.
"Dr. James Till’s work was not only essential to the discovery and conception of stem cells but also set a new standard for scientific rigour and collaboration,” said Dr. Brad Wouters, Executive Vice President of Science and Research at UHN. “His contributions will continue to resonate through the generations of scientists he mentored and the countless patients who have benefited from his discoveries.”
For more on Dr. Till’s work and enduring legacy, please see the following videos from UHN that marked the 50th anniversary of the discovery that confirmed the existence of stem cells: Till and McCulloch tribute "Mentors"; Till and McCulloch tribute “Legacy”.
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:
● Better Care for Movement Disorders: UHN researchers highlight the potential of a non-invasive treatment option for deep-brain stimulation for movement disorders like Parkinson Disease.
● Improving the Safety of Ventilation: Early trial finds nerve stimulation may protect breathing muscles in ventilated patients.
● AI Chatbot Enhances Cancer Care: A new AI chatbot offers on-demand support to people living with advanced breast cancer.
● Rhythms in Rehabilitation: Researchers explore dance as a form of physical rehabilitation during stroke recovery.
Read these stories and more online here. To read previous issues, see the newsletter archive.
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.
Learn more about our institutes by clicking below:
