In the operating room, a removed tumour can look deceptively uniform — like any other piece of tissue. But within it lies a bustling city of cancer cells, blood vessels, and connective tissue, invisible to the naked eye. Dr. Ralph DaCosta’s research team at UHN’s Princess Margaret Cancer Centre turns this hidden world into vivid colour, revealing cancer’s behaviour in real time.
His team discovered a dynamic, constantly changing tumour microenvironment surrounding pancreatic cancer cells (published in Science Advances), that could help oncologists tailor treatment schedules for patients who have one of Canada’s deadliest cancers.
"We saw pockets of pancreatic cancer cells that are inherently hypoxic — in other words, they have low oxygen levels. They are enveloped by very dense layers of connective tissue called collagen fibers, preventing blood vessels from getting inside,” Ralph describes.
To detect pockets of oxygen-starved (hypoxic) cancer cells, the team, led by former doctoral student Dr. Timothy Samuel, used a sophisticated combination of fluorescent labelling and advanced optical microscopy in living models of cancer to light up different components in the tumour microenvironment.
Cancer cells in preclinical models were engineered to glow red (DsRed) at all times, while a built-in hypoxia sensor made them glow green (GFP) only under low-oxygen conditions. Blood vessels were highlighted in cyan using a fluorescent antibody, allowing the team to measure oxygen access relative to blood supply. Meanwhile, collagen fibers—key components of the tumour’s stiff, fibrotic structure—were visualized using second harmonic generation microscopy, a special form of laser light that makes collagen fibers shine like white snow under a spotlight.
These rigid, oxygen-starved pockets of cancer emerge, persist, and can contribute to tumour progression: they may fuel a vicious cycle of tumour growth and spread by cutting off oxygen, reshaping collagen and the microenvironment over time, and helping cancer cells evade treatment.
In a follow-up study published in Scientific Reports, the team used this imaging platform to track how patient pancreatic tumour cells responded to radiation. After radiation treatment, fewer cells continued to glow red, indicating reduced viability of cancer cells, and there was a reduction in green fluorescence, signalling less hypoxia. The presence of DNA damage markers and slowed cell growth confirmed that the treatment was effective. Through quantitative analysis, the study also offered insights into optimizing treatment timing and dosing to improve treatment outcomes.
This imaging system gained widespread recognition that led to a collaboration with Drs. Mark Minden, John Dick, Stephanie Xie, and Tak Mak (and collaborators abroad), to illuminate how blood cancers interact with the immune system and respond to immunotherapy. This time, the team needed ways to visualize whether cancer cells were alive or dead to better track treatment response, as the bone marrow microenvironment is remodelled during disease progression. They developed a new marker for tumour cell death — a pink fluorescent signal that is emitted when the treatment kills a leukemia cell.
“We have also found ways to visualize different immune cell populations in the bone marrow where leukemia cells develop,” Ralph adds. “It will let us see an entirely different cellular landscape with complex microarchitecture, and the interaction between leukemia cells and immune cells. I’m very excited by this new frontier where imaging can play a key role in improving our understanding of tumour biology. This type of work has never been done before.”
Ralph’s obsession with the optical world started when he was a child, building a ruby crystal laser in his garage. The resulting laser beam was invisible — until he sprinkled talcum powder in the air and saw it glow red. For the first time, he felt the magic of visualizing the unseeable. That moment inspired him to learn more about light through physics and math.
From a summer job in Dr. Brian Wilson’s Lab at the Princess Margaret Cancer Centre, he redirected his path to cancer research.
“I came upon a newspaper article that stated how a star scientist, Dr. Brian Wilson, was coming from Hamilton to Toronto to start a whole new field of bio-photonics.” Ralph cold-called Brian to express his interest in studying light for medical applications, which led to his first job and eventually a PhD. In 2014, Ralph started his own independent research lab and became a colleague alongside his mentor.
From tinkering with a simple laser device in his garage, Ralph went on to design advanced optical tools for medicine, including confocal microscopes that reveal details in tissue and cell biopsies, and fluorescence-based endoscopes now used in clinics to help detect early cancers and guide surgeries with greater precision.
“It was also mind-blowing to me that the curious kid with a garage-built laser is now solving clinical problems that can affect people around the globe.”
One of his early projects in Brian’s Lab was to detect precancerous lesions in the gastrointestinal tract that could lead to colon cancer. Ralph built an imaging device using blue light to excite molecules inside cancerous tissues that would give off signals for flat adenomas, dangerous precursor lesions that are near impossible to detect by the unaided eye of the clinician.
“If there was a sign of colon cancer, it would light up green, but all I saw was red,” Ralph recalled one particularly serendipitous night when he was examining one tissue sample in the lab.
The red signal turned out to be bacteria, not cancer-related, which unleashed a whole new field of application for the use of fluorescence light imaging technology in wound care. Bacterial hotspots are known to delay wound healing and lead to infection. Ralph modified the technology into a novel handheld device to detect elevated bacteria levels and provide real-time wound care monitoring and treatment guidance. Based on this innovative research, he founded MolecuLight Inc. in 2012, to commercialize the patented product and help patients globally through its Toronto and U.S. offices, for which he was awarded UHN Inventor of the Year in 2013. For more information, Ralph shared his innovation journey on the Behind the Breakthrough Podcast.
Ralph’s curiosity extends far beyond the cancer research laboratory. He is an avid gardener who conducts botany experiments on his kitchen table to investigate how different plants can talk to each other at night, examining leaves under fluorescence light. He is also a fisherman who ties and tests his own flies.
“Many things that inspire me are not directly related to cancer,” says Ralph. “If you look at other systems in the world, biological or non-biological, it can teach you a wide range of different things.”
Ralph excels in drawing analogies from one field and applying them in a different place. He also encourages his students to “look beyond the desk” to broaden their perspective, avoid tunnel vision, and inform scientific thinking.
“I want my two young daughters to also become people who have this ability to look at something completely unrelated to their profession, and look at it from different perspectives to extract the information that matters to them,” says Ralph. “That is the art of discovery.”
Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.
Hosted by UHN’s Princess Margaret Cancer Centre (PM), the Allan Slaight Breakthrough Forum marked the first-ever C8 Symposium, uniting top cancer researchers from eight premier global cancer research institutes.
Held on September 15 and 16, 2025, at the MaRS Auditorium in Toronto, the C8 Symposium brought together leading scientists from cancer research institutions across Canada, Australia, France, Israel, Japan, the UK, and the USA. The event was made possible by the generous support of La Fondation Emmanuelle Gattuso and The Slaight Family Foundation through the Allan Slaight Breakthrough Fund.
The two-day symposium featured over 30 expert talks, moderated discussions, poster presentations, and networking sessions focused on cutting-edge topics such as chemotherapy resistance, synthetic lethality—a treatment approach that targets specific lethal mutations in cancer cells, novel therapeutic targets, and tumour microenvironment dynamics.
The sessions were led by internationally renowned researchers including Drs. Aaron Schimmer and Brad Wouters (PM), Dr. Ricky Johnstone (Peter MacCallum Cancer Centre), Dr. Robert Bristow (Manchester Cancer Research Centre), Dr. Kevin Haigis (Dana-Farber Cancer Institute), Dr. Shai Izraeli (Tel Aviv University), Dr. Steven Le Gouill (Institut Curie), and Dr. Wakako Toga (National Cancer Center Japan).
Opening remarks from Dr. Schimmer, Senior Scientist and Director of PM, set the tone for the symposium, emphasizing the importance of global collaboration in tackling the complexity of cancer. Throughout the event, speakers shared insights into newly discovered cancer-driving mechanisms, innovative therapeutic strategies, emerging technologies, and translational research platforms aimed at improving patient outcomes.
(Pictured from left to right) Panel discussion with Dr. Hiroyuki Mano, Dr. Steven Le Gouill, and Dr. Marianne Koritzinsky, moderated by Dr. Brad Wouters.
A highlight of the symposium was a panel discussion on accelerating cancer target discovery and drug development, inspired by Dr. Hiroyuki Mano’s (National Cancer Center, Japan) presentation on a novel model that has transformed cancer drug discovery. The session featured Dr. Marianne Koritzinsky (PM), who introduced a promising new protein target for cancer, and Dr. Le Gouill, who shared insights into targeted therapy in Mantle Cell Lymphoma, emphasizing biology-driven treatment design.
“We are excited about the potential of collaborating at the institutional level to tackle the biggest problems and biggest opportunities in cancer,” said Dr. Wouters, PM Senior Scientist and Executive Vice President of Science and Research at UHN. “By aligning our institutional strengths, we can create environments that foster innovation, streamline discovery, and deliver impact at scale.”
The symposium also featured a poster session designed to spotlight the work of postdoctoral and emerging researchers, providing a valuable platform for the next generation of cancer scientists to showcase their research to an international audience.
The symposium concluded with a Leadership Summit focused on strategic planning for future C8 initiatives, including mentorship, capacity-building, and global alignment of comprehensive cancer centres. Discussions led by institutional leaders explored ways to support the cancer research workforce and foster international team science.
“This inaugural C8 Symposium marks a pivotal moment in global cancer collaboration,” said Dr. Schimmer. “By bringing together diverse expertise and perspectives, we are laying the foundation for transformative research that will shape the future of cancer care.”
Participants from the Allan Slaight Breakthrough Forum: Inaugural C8 Symposium
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 Grading for Brain Cancer: Study identifies a biomarker that improves grading of the most common brain tumours.
● Race Matters in Recovery: Researchers find that Black patients face more complications following urologic cancer surgery.
● Pinpointing Chatty Cells: New AI tool maps complex conversations between cells in cancer and other diseases.
● New Cell Therapy for Type 1 Diabetes: Early trial at UHN shows that new diabetes treatment may restore insulin production.
Read these stories and more online here. To read previous issues, see the newsletter archive.
Dr. John Dick, Senior Scientist at UHN’s Princess Margaret Cancer Centre and University Professor at the University of Toronto, has been named a 2025 Clarivate Citation Laureate. Clarivate’s selection process recognizes influential, highly cited researchers — an international recognition often associated with future Nobel Prize recipients. He is the only Canadian among this year’s 22 laureates, split among the fields highlighted by the four Nobel Prizes.
Dr. Dick’s research identified leukemia stem cells, a small group of leukemic cells that have stem cell properties that allow them to sustain long-term leukemia cell growth, survive treatment, and drive future disease relapse. This work helped explain why many cancers return after therapy. By showing that these stem cells play a role in disease recurrence, his research influenced the discovery of cancer stem cells in many solid cancers and shaped how scientists approach cancer biology and treatment strategies.
Further underscoring his stature in the scientific community, Dr. Dick also received the 2024 Lifetime Contribution Prize from the Canadian Cancer Society earlier this year and was elected as an International Member of the National Academy of Sciences, among other recognitions.
At UHN, Dr. Dick holds the Helga and Antonio De Gasperis Chair in Blood Cancer Stem Cell Research. He is also a Professor in the Department of Molecular Genetics and holds the distinction of University Professor at the University of Toronto. His laboratory continues to study the sequence of events that lead from the normal cell of origin to leukemia stem cells, why these stem cells resist treatment, and how they might be targeted to improve long-term outcomes.
Clarivate, the organization behind the Citation Laureates, has recognized only 465 researchers worldwide since 2002, and 75 Citation Laureates have later received Nobel Prizes.
See here for the full announcement.
The CenteR for Advancing Neurotechnological Innovation to Application (CRANIA) held a ceremony for its inaugural Dean Connor and Maris Uffelmann CRANIA Innovation Awards in Neuromodulation earlier this year at the Krembil Discovery Tower at UHN’s Toronto Western Hospital.
These awards were established through a generous donation from Dean Connor and Maris Uffelmann to foster collaboration and innovation in research on neuromodulation—using electrical or magnetic signals to regulate nerve activity and treat neurological conditions. “These awards foster interdisciplinary partnerships in neuromodulation and accelerate the translation of innovative research into solutions that profoundly improve patient outcomes," said Dr. Luka Milosevic, CRANIA co-Director.
As the inaugural recipients, the following projects received up to $75,000 to support innovative research in neural repair, deep brain stimulation (DBS), and shockwave therapy:
Project A | Title: Examining the Activation and Integration of Resident Neural Stem Cells in the Stroke-Injured Brain Following Electrical Stimulation: A Novel Approach to Promote Neural Repair
Dr. Cindi Morshead, Affiliate Scientist at UHN’s KITE Research Institute (KITE), and Dr. Bojana Stefanovic, Senior Scientist at Sunnybrook Research Institute, co-lead a project investigating how electrical stimulation can activate neural stem and progenitor cells (NSPC) for neural repair following a stroke. Using advanced imaging techniques, this research supports the development of new therapeutic strategies for stroke rehabilitation.
Project B | Title: Advanced Mid-Field (0.5T) MRI for Enhanced DBS Targeting and Lead Localization Improving Patient Care
Dr. Ian Connell, Affiliate Scientist at KITE, and Dr. Jürgen Germann, Assistant Scientist at UHN’s Krembil Brain Institute, co-lead a study to improve the precision of DBS procedures—a critical treatment for Parkinson disease and other neurological conditions. By using advanced magnetic resonance imaging (MRI), the project aims to enhance surgical imaging and electrode placement accuracy, ultimately improving patient outcomes.
Project C | Title: The Safety and Efficacy of Extracorporeal Shock Wave Therapy in Individuals Living with Chronic Spinal Cord Injury: A Prospective Pilot Study
Dr. Julio Furlan, Scientist at KITE, and Dr. José Zariffa, Senior Scientist at KITE, co-lead a study exploring the use of extracorporeal shockwave therapy (ESWT)—a non-invasive neuromodulation treatment using soundwaves—to improve neurological and functional recovery and mitigate secondary health conditions in individuals with chronic spinal cord injury. The research seeks to confirm the safety and collect preliminary data on the efficacy of ESWT and provide a foundation for future clinical trials.
“These awards mark a key milestone in our commitment to supporting bold new ideas and collaborative excellence, paving the way for future discoveries and major research initiatives,” said CRANIA co-Director, Dr. Taufik Valiante. The second round of applications has closed, and the adjudication process is currently underway.
During the ceremony, Dean Connor and Maris Uffelmann were also presented with UHN Foundation’s Gold Upper Canada Medal. This medal recognizes distinguished service and generous support.
Read more about the establishment of the CRANIA Awards here.
The Upper Canada Medal, originally created by the Loyal and Patriotic Society of Upper Canada, recognized the service of volunteer soldiers in the War of 1812. Recognizing an even greater need, the Society decided in 1819 to reduce the medals to gold bullion and establish a trust fund to support the construction of the original Toronto General Hospital, which opened to patients in 1829. Today, UHN Foundation honours special donors by awarding these medals in recognition of their distinguished philanthropic support.
"If we want to better help patients’ recovery, we need to broaden the way we evaluate them following treatment for autoimmune encephalitis. Mental health is a critical part of long-term recovery that has long been underappreciated in studies,” says Dr. Julien Hébert, lead author of a new study from UHN’s Krembil Brain Institute (KBI) looking at how to better evaluate mental health outcomes after autoimmune encephalitis (AE).
AE is a serious condition in which the immune system mistakenly attacks the brain, leading to inflammation of brain tissue. This inflammation disrupts normal brain function and can lead to memory problems, changes in mood or behaviour, and psychiatric symptoms such as anxiety or depression.
Although the psychiatric effects of AE are recognized, widely used standards for measuring them have not existed until now. To address this gap, the KBI team compared three patient-completed questionnaires with a structured, clinician-led interview—the Mini Neuropsychiatric Inventory 7.0.2 (MINI)—in 35 individuals recovering from AE.
The study found the MINI identified psychiatric symptoms in 71% of participants, compared with only 23% to 50% when using self-report measures. Adapting the threshold used in these questionnaires to diagnose mental health concerns did pick up more cases, but it came at the cost of decreased accuracy. Among the tools tested, the Profiles of Mood States-2 (POMS-2) questionnaire struck the best balance between accuracy and practicality after adjustments.
The researchers also noted that while the MINI is thorough, it takes much longer to complete than self-report forms. “We must balance sensitivity and specificity with feasibility,” notes the study’s senior author, Dr. David Tang-Wai. “Combining clinician-led and self-report assessments may be the best approach, and refining how we use self-report tools can help ensure fewer patients with psychiatric needs are missed.”
These findings highlight that recovery after AE is not just about regaining physical independence—it’s also about restoring mental health. By closing these gaps, this research lays the groundwork for more timely interventions—helping prevent suffering and improving long-term recovery for survivors.
The first author of this study is Dr. Julien Hébert, a Clinician Investigator at the Krembil Brain Institute and an Assistant Professor in the Temerty Faculty of Medicine at the University of Toronto.
The senior author of this study is Dr. David Tang-Wai, a Clinician Investigator at the Krembil Brain Institute, Co-Director of UHN’s Memory Clinic, a Professor in Neurology and Geriatric Medicine at the University of Toronto, and Division Director of Neurology in the Department of Medicine at the University of Toronto.
Dr. Dilip Koshy also contributed invaluably to this study. Dr. Koshy is a psychiatrist in the Neuropsychiatry Clinic with UHN’s Mental Health Program, and an Assistant Professor in the Department of Psychiatry with the Temerty Faculty of Medicine at the University of Toronto.
This work was supported by UHN Foundation.
Dr. Hébert receives funding from the International Autoimmune Encephalitis Society outside of the work herein. For a list of other competing interests, see the publication.
Hébert J, Gabarin R, Lee S, Koshy D, Day GS, Lapointe S, Climans SA, Muccilli A, Patel PS, Pleshkevich M, Xia D, Steriade C, Tang-Wai DF. Measuring long-term psychiatric outcomes in post-acute autoimmune encephalitis. J Affect Disord. 2025 Jul 27;391:119978. doi: 10.1016/j.jad.2025.119978.
I am currently a postdoctoral researcher in the Environments Aging Biomechanics Lab (EnABL) at UHN’s KITE Research Institute. As a postdoctoral researcher, I am responsible for conducting independent research and mentoring students.
I started this role in October 2024, a week after defending my PhD thesis.
For my postdoctoral research, I am leading a study that tests the impact of different aftermarket non-slip products—such as bathmats—on slipping risk, as well as movement strategies that young and aging adults could use to help prevent slips while bathing depending on how slippery they perceive their environment to be. With this project, we hope to be able to make practical recommendations that can help people select non-slip products to improve bathing safety.
Prior to starting at UHN, I completed my PhD at the University of Saskatchewan, where my research examined the influence of the individual, task, and environment on balance control while walking. We used an inertial measurement unit-based motion capture system to take complex measurements of balance control outside of the lab. My graduate research has led to multiple peer-reviewed publications that emphasize the importance of considering factors such as location (e.g., walking in a lab versus outside) and sex in walking assessments.
Outside of my postdoctoral and graduate research, I have been involved in a research project aimed at establishing the current state of sex- and gender-based analysis in standing and walking research. Ultimately, this research aims to improve the inclusivity of current practices in standing and walking biomechanics research.
In my role, I have the opportunity to lead research that could have a positive impact on the health and well-being of others. Additionally, my role has afforded me the opportunity to mentor several undergraduate students. Making an impact through research and mentorship is something I am passionate about. Health research is very important to me, and with Canada's aging population, researching ways to improve the health and well-being of others is vital.
My research testing the effectiveness of non-slip products for bathing environments helps advance UHN’s vision because it may lead to recommendations that improve safety and accessibility in the bathroom. The non-slip products tested, such as suction cup bathmats, are affordable in comparison to other options like grab bars and do not require permanent modifications. As a result, these products could offer a way to make bathing safer without being prohibited by cost, space, or living arrangements. This could allow more Canadians to age in place, as bathing is one of the first activities of daily living in which people often lose independence and may require support outside of their current homes or living spaces.
The unique facilities at UHN and its proximity to patient populations allow us to answer complex research questions and translate those findings into meaningful outcomes.
Outside of work, I enjoy trying new foods and attending cultural celebrations with my fiancé, Kaitlyn. As newcomers to Toronto, we have also become quite the pair of Blue Jays fans.
I hope to see more equitable and inclusive research practices. As I continue to learn more about the amazing research at UHN that is moving us in this direction, I feel hopeful and excited about the future of health research.
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).
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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