Expanding the Reach of CAR T

New approach to specialized cancer immunotherapy may improve precision and broaden impact.

Image Caption: Cancer immunotherapies, like CAR T, train immune cells to recognize cancer-specific targets. One way they do this is by targeting small pieces of cancer proteins that are displayed on the cell surface by molecules called HLA. Researchers are trying to improve the specificity and effectiveness of this approach.

Chimeric antigen receptor T cell therapy (CAR T) has transformed the treatment of certain blood cancers. However, this approach has been difficult to apply to other cancers, such as solid tumours. Researchers at UHN’s Princess Margaret Cancer Centre (PM) have identified a new CAR T strategy that can target a protein found in many cancer cells, potentially broadening its application to more cancer types.

CAR T is a cancer immunotherapy that works by harnessing and reprogramming a patient’s own immune cells to recognize and attack cancer cells. A major challenge of these therapies is identifying suitable targets that are also unique to cancer cells.

CAR T therapies are designed to recognize and target specific proteins on the surface of cancer cells (surface antigens). This can be a limitation of the therapy as it is challenging to identify surface targets that are specific to cancer cells. In addition, these therapies often target protein fragments presented by human leukocyte antigen (HLA) Class I molecules on cell surfaces. However, HLA Class I molecules are found on most cells, making it difficult to distinguish cancer cells from healthy cells, increasing the risk that these therapies will also affect healthy tissue.

Researchers have begun exploring protein fragments presented by HLA Class II molecules—which are found on fewer healthy cells but can be present at higher levels on some cancer cells.

Wilms tumour 1 (WT1) is a protein found inside cells that has been associated with many cancers, including leukemia. Because conventional CAR T cells typically recognize proteins on cell surfaces, WT1 has been difficult to target using this approach. PM researchers have developed a new approach, designing CAR T cells that recognize WT1 protein fragments presented by HLA Class II molecules.

In laboratory studies, the engineered CAR T cells successfully identified and attacked leukemia cells that presented WT1 fragments through HLA Class II molecules. The therapy showed strong anti-cancer activity both in cell-based experiments and preclinical models, while selectively targeting cancer cells. The WT1-CAR T cells only recognized and attacked cancer cells when both WT1 and HLA Class II molecules were present together.

Most immune therapies that target proteins presented by HLA molecules are restricted to a specific HLA type, limiting the patients who may be eligible for treatment. However, this new WT1-CAR T was able to recognize the WT1 protein fragment when it was presented by 18 of the 20 HLA Class II molecules tested. This could make the approach applicable to a broader and more genetically diverse group of patients.

While further research and clinical testing are needed, this approach could expand CAR T cell therapy beyond its current applications, offering new treatment possibilities for people with myeloid leukemia and other cancers, such as ovarian cancers and mesothelioma, that have remained difficult to treat.

Evey Zheng, a Doctoral Candidate at UHN’s Princess Margaret Cancer Centre, is the co-first author of the study.

Dr. Chung-Hsi Wang, a Postdoctoral Research at UHN’s Princess Margaret Cancer Centre at the time of the study, is the co-first author of the study.

Dr. Naoto Hirano is a Senior Scientist at UHN’s Princess Margaret Cancer Centre and a Professor in Immunology at the University of Toronto. He is the corresponding author of the study.

This work was supported by the Canadian Institutes of Health Research, the Longo Family Cancer Foundation, the Ira Schneider Memorial Cancer Research Foundation, and The Princess Margaret Cancer Foundation.

Dr. Naoto Hirano is Tier 1 Canada Research Chair in Immunology to Immunotherapy.

Dr. Hirano reports a patent for Anti-WT1 Antigen-Binding Proteins and Uses Thereof pending.

Zheng EYF, Wang CH, Ochi T, Ohashi Y, Ihara F, Fukao S, Ito Y, Boukhaled GM, Wang BX, Han DH, Wei X, Yolmo P, Burt BD, Saso K, Matsunaga Y, Ly D, Kagoya Y, Butler MO, Minden MD, Hirano N. CAR T Cells Targeting an Intracellular Leukemia Antigen Promiscuously Presented by Diverse HLA-II Alleles. Blood Cancer Discov. 2026 Sep 3;7(5):813-828. doi: 10.1158/2643-3230.BCD-25-0230.
(link is externalBlood Cancer Discov. 2026 Sep 3;7(5):813-828. doi: 10.1158/2643-3230.BCD-25-0230. Blood Cancer Discov. 2026 Sep 3;7(5):813-828. doi: 10.1158/2643-3230.BCD-25-0230. Blood Cancer Discov. 2026 Sep 3;7(5):813-828. doi: 10.1158/2643-3230.BCD-25-0230.

Exploring Safer Hospital Discharges

New study shows how community warming centres have the potential to reduce hospital burden.

Image Caption: Overcrowding in emergency departments can lead to issues such as increases in mortality and staff distress. Inadequate sheltering options contribute to overcrowding as hospital discharge for those experiencing unsheltered homelessness is unsafe during the winter.

People experiencing homelessness often visit emergency departments (EDs) as a source of shelter, particularly during the colder months. Researchers at UHN found that hospital-affiliated warming centres, operated in collaboration with community partners, have the potential to reduce ED length of stay for people experiencing homelessness.

In Toronto, rates of non-urgent ED visits by people experiencing homelessness during winter months have been increasing. This is often due to limited sheltering options, as people experiencing homelessness may seek care in the ED for a range of concerns, including access to shelter.

Following an ED visit, people experiencing unsheltered homelessness may face barriers to accessing shelter beds and other safe discharge locations. Due to the medical risks associated with discharge to an unsafe environment, this can result in patients remaining in the ED even after their medical needs have been addressed. This delay contributes to ED overcrowding, which causes reduced service quality, increased risk of mortality, and greater staff distress.

As the number of people experiencing homelessness continues to rise, identifying safe discharge options is becoming increasingly important to help reduce ED overcrowding while ensuring patients receive appropriate support after leaving the hospital. To address this need, UHN’s Social Medicine program worked with community partners to establish a hospital-affiliated warming centre in Toronto in 2023 to provide a safe location for discharges during the winter months.

To examine the impact of this warming centre, the researchers looked at the relationship between ED visits by people experiencing homelessness and the operation of the Toronto-based hospital-affiliated warming centre. This warming centre were operated in collaboration with a community partner with expertise in supporting people experiencing homelessness. The team analyzed administrative data on ED and hospital-affiliated warming centre utilization from the winter seasons between November 2022 and April 2025.

The research team found that the hospital-affiliated warming centre supported 1,196 visits during its first year and 638 visits during the second year. In the second year, when a referral pathway from the ED to the warming centre was open, it was associated with decreased ED lengths of stay. This suggests that the referral pathway may have helped facilitate faster discharges.

The study also found that in the second year, municipal shelter system volumes correlated with ED length of stay, suggesting that shelter capacity may influence patient flow in the ED.

Overall, the researchers say that hospital-affiliated warming centres have the potential to reduce ED burden. More research and monitoring of these interventions are needed to ensure optimal outcomes.  The researchers note that improved access to emergency shelter beds and affordable and supportive housing is necessary to improve the health of people experiencing homelessness.

Dr. Nick Kerman, Research Associate with the Gattuso Centre for Social Medicine at UHN, and Clinical Psychologist at UHN, is the first author of the study.

Dr. Kate Hayman, Clinician Investigator and emergency physician at UHN, is the corresponding author of the study. She is an Assistant Professor in the Department of Medicine at the University of Toronto.

This work was supported by UHN’s STAR-EM (Summer Training and Research in Emergency Medicine) program and UHN Foundation. The warming centre was developed and delivered through collaboration among UHN Emergency Medicine, the Gattuso Centre for Social Medicine at UHN, and a community partner with expertise supporting people experiencing homelessness.

Kerman N, Yanikomeroglu S, Ragusila A, Vitkin N, Coyle S, Steer L, Boozary A, Hayman K. Development of a hospital-affiliated warming centre to reduce emergency department pressures among patients experiencing homelessness. CJEM. 2026 Aug 10. doi: 10.1007/s43678-026-01250-y. Epub ahead of print. 

Excellence in Physician-Led Research

Drs. Bhat and Howe receive SUMO–UHN Distinguished Physician Investigator Awards.

Image Caption: Dr. Mamatha Bhat is a transplant clinician–scientist at UHN’s Ajmera Transplant Centre, and Dr. Kathryn Howe is a vascular surgeon–scientist at UHN’s Peter Munk Cardiac Centre.

Two outstanding clinician–scientists—Dr. Mamatha Bhat and Dr. Kathryn Howe—have been named the inaugural recipients of the SUMO–UHN Distinguished Physician Investigator Award, a strategic salary support award designed to retain exceptional mid-career physician-researchers while accelerating health innovation at UHN.

Dr. Bhat, a transplant hepatologist and clinician-scientist at UHN’s Ajmera Transplant Centre, leads an internationally recognized research program focused on developing and translating artificial intelligence (AI) into clinical practice in transplantation. Her research aims to make access to liver transplantation more equitable and to improve outcomes across the transplant journey, from supporting complex decisions about transplant candidacy and organ allocation to predicting post-transplant complications and detecting early graft injury before irreversible damage occurs. With support from the SUMO–UHN Award, Dr. Bhat will accelerate the prospective evaluation and clinical deployment of AI-powered decision-support systems, integrating these tools into real-world transplant workflows and evaluating their safety, effectiveness, and impact on patient care. This work will provide a framework for the responsible implementation and scaling of AI across transplant programs in Canada and internationally, while strengthening UHN’s position as a global leader in translating AI innovation into clinical care.

Dr. Howe is pursuing a bold new approach to treat atherosclerosis, a buildup of plaque in blood vessels that underlies cardiovascular diseases such as heart attacks and stroke. As a vascular surgeon–scientist at UHN’s Peter Munk Cardiac Centre, Dr. Howe leads an innovative research program aimed at improving our understanding of how the cells that line blood vessels communicate with surrounding tissues. Her team is developing a novel precision medicine platform to deliver targeted treatments directly into diseased blood vessel walls. Funding from the award will support this work, ultimately aiming to prevent the development of cardiovascular disease, which remains one of the leading causes of disease burden worldwide.

This award was established as a unique partnership between the Sinai–UHN Academic Medical Organization (SUMO) and UHN's Canada Leads initiative to strengthen UHN's leadership in translational research, clinical innovation, commercialization, and knowledge mobilization. It was designed to support visionary clinician–scientists whose work bridges scientific discovery and patient care, while helping to strengthen UHN's leadership in translational research, clinical innovation, commercialization, and knowledge mobilization.

“Initially designed to support only one award, the exceptional caliber of these two applicants motivated SUMO and the Canada Leads program to double their commitments and recognize both awardees,” says Dr. Paul Tenenbein, Chair of SUMO. “This demonstrates the research excellence among our physicians at UHN, and their dedication to advancing the development of novel, high-impact approaches to healthcare delivery. SUMO is pleased to partner with UHN on this award, and hope that it serves as a model for future opportunities to support academic physicians.”

• Related: Read more about SUMO’s impact “Powering Physician Innovation | UHN Research”

A key focus of the award is supporting mid-career researchers, who play a vital role in driving innovation and mentoring the next generation of scientists but often have fewer dedicated funding opportunities. “By investing in researchers at this pivotal stage in their careers, the award helps them expand the scope and impact of their work while strengthening UHN's long-term research capacity and leadership,” says Dr. Brad Wouters, Executive Vice President of Science & Research at UHN. “It also creates the conditions for bold ideas to move more quickly from the laboratory and clinic into real-world solutions that benefit patients and health systems alike, reflecting a core goal of the Canada Leads program and UHN's unique opportunity to translate made-in-Canada discoveries into global impact.”

Drs. Bhat and Howe will each receive $500,000 over five years to dedicate more time to research that can transform patient care and generate long-term impact for the health system. As the co-recipients of this award, Drs. Bhat and Howe exemplify the excellence of UHN’s world-class research community, and the dedication that it has towards tackling complex health care challenges through interdisciplinary and collaborative science. Congratulations to Drs. Bhat and Howe.

For more information on SUMO’s commitment to supporting academic physicians, visit the SUMO website.

Research Spotlight

Read the latest bi-monthly newsletter that highlights advancements from UHN researchers.

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:

● A New Avenue for Bipolar Depression: Researchers report rapid symptom relief with repeated ketamine infusions.

● Assessing Kidney Disease Globally: Kidney disease worsens outcomes for patient hospitalized with cirrhosis; study finds.

● Unlocking Therapeutic Potential: Establishing a new AI tool to identify cancer-responsive T cell receptors.

● Retaining a Vital Nursing Workforce: Clearer roles and stronger career support could help retain registered practical nurses.

Read these stories and more online here. To read previous issues, see the newsletter archive.

Fernanda @TeamUHN

Dr. Fernanda Yamamoto Ricardo da Silva is a Postdoctoral Researcher at UHN.

Tell us about your role at UHN.

I am a Postdoctoral Researcher in Dr. Mingyao Liu’s lab at UHN's Latner Thoracic Research Laboratories at the Ajmera Transplant Centre. We focus on cellular and molecular mechanisms of tissue damage that occurs in lung transplantation due to the return of blood flow to areas deprived of oxygen—a process known as ischemia reperfusion injury. Using cell culture and experimental models, we are developing new organ preservation solutions, as well as a new perfusion solution for Ex Vivo Lung Perfusion (EVLP)—a procedure in which the lungs are preserved outside of the body and assessed for transplantation.

How long have you been at UHN and what led you to this role?

I started my position at UHN around a year ago. I'm a Brazilian biologist with a Master's degree in Pharmacology from the Universidade de São Paulo in Brazil, where I studied the role of the estradiol hormone in the inflammatory effects of ischemia-reperfusion injury. I then completed a double PhD through the Universidade de São Paulo and the University Medical Center Groningen in the Netherlands. My work focused on sex differences and lung inflammation, specifically in lung transplantation.

What are you passionate about in your role at UHN? What does health research mean to you?

It’s rewarding to know that all of the research we do, whether big or small, is part of a larger effort to improve patient care. Even when experiments don’t go as planned, we push through and can get amazing discoveries.

How does your work help to advance UHN's vision of A Healthier World?

Lung transplantation is a potentially lifesaving procedure for certain patients, but there is a shortage of acceptable donor lungs, as well as other complications that can limit the success of these procedures. My work aims to improve lung transplantation in the hopes of achieving better patient outcomes.

What makes UHN an ideal place to advance health research?

There is such a diverse group of people who work at UHN. When people with different backgrounds and specialties come together, it leads to new ideas and solutions in ways that might not emerge otherwise.

Tell us an interesting fact people don’t know about you.

When I was a kid, I learned how to do acrobatics like those seen in Cirque du Soleil. I could do trapeze, aerial silks, and even juggling.

What do you see for the future of health research, and what gets you excited about it?

In the future, I believe that we will have more tailored and personalized medicine that takes into account individual characteristics. This has the potential to lead to more effective and patient-centred health care.

How to Participate in You @TeamUHN

You @TeamUHN is a campaign to highlight the important scientific contributions that research lab staff, trainees and learners, administrative staff, core facilities staff, Research Solutions & Services staff, and volunteers make towards A Healthier World through discovery and innovation. If you’re interested in sharing your story, we invite you to complete this form here (Open to UHN staff, trainees, and volunteers).

Ambika @TeamUHN

Dr. Ambika Bansal is a Postdoctoral Researcher at UHN’s KITE Research Institute.

Tell us about your role at UHN.

I am a Postdoctoral Researcher at UHN’s KITE Research Institute (KITE) and a recruit from the Canada Leads program. I am in Dr. Behrang Keshavarz’s lab where I specialize in neuroscience with expertise in motion sickness, multisensory integration, and driving safety.

My day-to-day work involves designing and conducting behavioural research studies in collaboration with other researchers and clinicians, analyzing and interpreting data, and translating our findings into knowledge that can ultimately help improve human health.

How long have you been at UHN and what led you to this role?

I have been at UHN for around nine months. I have my master’s and PhD in Neuroscience from the Centre for Vision Research at York University, where I studied how the brain uses sensory information to perceive our movement and navigate through the world.

My past research ranged from understanding how we learn and adapt our movements to exploring how our perception of self-motion changes in different environments, including how astronauts perceive their movement aboard the International Space Station. This work sparked my interest in how conflicts in sensory information can affect how we feel and function, particularly through experiences like motion sickness. My role at UHN was a natural next step, giving me the opportunity to build on this research while exploring its real-world applications.

What are you passionate about in your role at UHN? What does health research mean to you?

I am passionate about advancing sensory-motor research that can be applied to areas such as aging and rehabilitation technology. What excites me most about health research is the opportunity to take fundamental questions about how the brain works and connect them to challenges that affect people’s everyday lives. I am particularly passionate about understanding how our sensory systems shape perception and movement, and how emerging technologies can help us better understand, assess, and potentially rehabilitate these systems. To me, health research means combining curiosity with a clear purpose of generating knowledge that can ultimately improve people's health and quality of life.

How does your work help to advance UHN's vision of A Healthier World?

My work contributes to UHN’s vision of A Healthier World by aiming to understand the brain and the sensory processes that allow us to safely perceive, navigate, and interact with our surroundings. By studying these processes and exploring how technologies such as virtual reality and driving simulators can be used in research and rehabilitation, I hope to bridge the gap between our understanding of the brain and practical approaches that support healthy aging, rehabilitation, and mobility.

What makes UHN an ideal place to advance health research?

UHN, and in particular KITE, provides a unique environment where rehabilitation science, technology, and clinical expertise come together to address real-world health challenges. I am particularly excited to work within KITE’s Challenging Environment Assessment Laboratory (CEAL), where state-of-the-art facilities enable us to safely recreate complex, real-world conditions and study how people perceive, move, and respond to their environments.

For my research in multisensory integration, motion sickness, and driving safety, having access to these facilities alongside an interdisciplinary community of scientists, clinicians, engineers, and trainees creates opportunities to translate fundamental neuroscience into meaningful solutions for aging and rehabilitation.

Tell us an interesting fact people don’t know about you. Do you have any hobbies or interests outside of work?

One interesting fact people might not know about me is that I was on the varsity squash team during my undergraduate and master's programs. Outside of work, I love hiking, gardening, and exploring Toronto's incredible food and music scenes.

What do you see for the future of health research, and what gets you excited about it?

I see the future of health research becoming increasingly interdisciplinary, with new technologies enabling us to study human health in ways that were not previously possible. I am particularly excited by the potential of emerging technologies to create more precise ways of understanding, assessing, and supporting brain and sensory function.

How to Participate in You @TeamUHN

You @TeamUHN is a campaign to highlight the important scientific contributions that research lab staff, trainees and learners, administrative staff, core facilities staff, Research Solutions & Services staff, and volunteers make towards A Healthier World through discovery and innovation. If you’re interested in sharing your story, we invite you to complete this form here (Open to UHN staff, trainees and volunteers).

Francesco @TeamUHN

Dr. Francesco Rugolo is a Postdoctoral Researcher at UHN.

Tell us about your role at UHN.

I am a Postdoctoral Researcher in Dr. Moumita Barua’s lab at UHN’s Organ Systems & Integrated Health Sciences Research Institute. My research combines molecular and cellular biology, experimental models, and genomic and bioinformatics analyses to investigate the mechanisms underlying genetic kidney disorders.

How long have you been in this role?

I have been in the Barua lab since July 2025. Before joining the lab, I held my first Postdoctoral Researcher position in Dr. Tak Mak’s lab at UHN’s Princess Margaret Cancer Centre, studying how a specific signalling molecule from immune cells regulates skin inflammation, tumour development, and liver regeneration. I completed my PhD in Biochemistry and Molecular Biology from the University of Rome Tor Vergata, where my research examined how the metabolism of fats and the regulation of gene expression influence cancer development and cell differentiation, including the identification of a prognostic marker for neuroblastoma.

What are you working on at UHN?

At UHN, I am studying the molecular mechanisms of genetic kidney disorders, with a particular focus on the repair of the tiny filtering units of the kidney, called glomeruli, and the regeneration of podocytes—specialized kidney cells that form a barrier for blood filtration. I am also working on identifying potential biomarkers and therapeutic targets of kidney disorders.

What are you passionate about in your role at UHN? What does health research mean to you?

What excites me most about working at UHN is being in an environment where fundamental biological questions remain closely connected to patients and their needs. Our work begins with a simple but important question: when the kidney is damaged, what mechanisms support its repair, and how can proper function be restored?

I especially enjoy moving between laboratory experiments and complex datasets, following small clues until they begin to reveal a larger biological story. To me, health research means pursuing those clues with curiosity and rigour until they can improve our understanding of disease and how we treat it.

What makes UHN an ideal place to advance health research?

UHN is an ideal place to advance health research because you have the opportunity to work and collaborate with people who have different experience and expertise. UHN brings together world-leading scientists, clinicians, trainees, and patients within a highly collaborative research hospital network. I particularly value the opportunity to connect fundamental genetic discoveries with clinical expertise and patient needs, helping accelerate the translation of research findings into improved diagnosis, treatment, and care.

UHN’s multidisciplinary environment, advanced research infrastructure, and strong culture of innovation provide the resources and partnerships needed to address complex health challenges.

How does your work help to advance UHN's vision of A Healthier World?

My work contributes to UHN’s vision of A Healthier World by trying to understand why the kidney loses its ability to repair itself and whether that capacity can be restored. In the Barua Lab, we study how the gene PAX2 (Paired box gene 2) and related molecular pathways influence podocyte regeneration and the progression of genetic glomerular disease.

By combining experimental models with genomic data, we hope to uncover mechanisms that could lead to better biomarkers and, eventually, new therapeutic strategies. For me, advancing A Healthier World means turning discoveries at the bench into possibilities that could one day improve the lives of people living with kidney disease.

Do you have any interests outside of work?

Outside of science, I enjoy playing video games and reading books—I think of these as “active” hobbies because they require active engagement. If you fall asleep during a movie, it continues without you, but a book or video game cannot move forward unless you are engaged.

Over the past few years, I have also become increasingly interested in experimenting with new AI tools. AI has changed the way I approach everyday problems: when I need something, my first instinct is now to see whether I can build it myself, and I often enjoy the process of creating it as much as the final result.

What do you see for the future of health research, and what gets you excited about it?

I see the integration of AI with biology and health research as one of the greatest opportunities we have had in recent decades to advance our understanding of human health and disease. AI can help us identify patterns across complex genetic, molecular, and clinical data that would be difficult to recognize through traditional approaches alone. What excites me most is its potential to not only make research faster, but help us ask better questions and uncover connections that we might otherwise miss. I believe the greatest advances will come from combining these capabilities with biological expertise, rigorous experimentation, and a clear focus on meaningful outcomes for patients.

How to Participate in You @TeamUHN

You @TeamUHN is a campaign to highlight the important scientific contributions that research lab staff, trainees and learners, administrative staff, core facilities staff, Research Solutions & Services staff, and volunteers make towards A Healthier World through discovery and innovation. If you’re interested in sharing your story, we invite you to complete this form here(link is external) (Open to UHN staff, trainees, and volunteers).