As a teenager in his home country, Morocco, Razq Hakem watched his grandmother suffer from an agonizing disease.
His family tried to shield him from the sadness of the situation. Years later, he learned she died of ovarian cancer.
While completing his PhD in France at the University of Aix-Marseille II, he also found out that two aunts and other relatives had developed aggressive breast cancers at unusually young ages.
“I didn’t know what subtype of cancer they had,” he recalls, “but it was similar to BRCA1-mutated cancer, which is also my research focus.”
These early encounters planted the seeds of a lifelong mission: to understand the genetic roots of cancer and to find ways to stop it.
Today, Dr. Razq Hakem is a Senior Scientist and the Lee K. and Margaret Lau Chair in Breast Cancer Research at UHN’s Princess Margaret Cancer Centre, recognized globally for his breakthrough work on BRCA1 and BRCA2 mutations and DNA repair mechanisms.
In the 1990s, scientists recognized that women carrying mutations on the BRCA1 or BRCA2 genes had higher risks for cancer, but they lacked conclusive evidence linking the loss of these genes to specific cancers.
At that time, Razq had completed a PhD in immunology in France and a postdoctoral training program in immunology and genetics in the U.S. He arrived in Toronto in September 1994 to study the roles of BRCA genes in preclinical models and to uncover how their mutations are associated with cancer.
“Several top-tier laboratories were racing to publish the earliest discoveries related to BRCA1 mutations,” Razq remembers the fierce competition, and he was undeterred.
He deleted the BRCA1 gene in lab models, and the effects were detrimental. The team discovered that the loss of BRCA1 results in DNA damage, cell cycle arrest, and halted proliferation, rendering cells unable to survive.
Despite the exciting finding, Razq was frustrated as he could not study BRCA1 associated cancers, given that the cells in the lab models were dying prematurely. Therefore, he modified his experiments and deleted BRCA1 only in the mammary glands. After the modification, He observed a high incidence of mammary tumours, clearly indicating that the BRCA1 gene suppresses tumour growth in breast tissue, and that its mutations predispose for breast cancer.
He published these landmark results in Cell in 1996, and Genes & Development in 2004, followed by a series of studies that altered the global research focus toward understanding BRCA1’s role in DNA damage repair, replication stress and tumour suppression, which paved the way for targeted therapies.
“We were among the first groups worldwide to demonstrate the harmful effects of BRCA mutations and their link to breast cancer in preclinical models,” says Razq. “I am very proud of our achievements and grateful to our national and international collaborators.”
Razq’s lab has identified several potential therapeutic targets for treating cancers associated with BRCA1 and BRCA2 mutations, two of which, RNF 8 and RNF168, are moving along the drug development pipeline.
His lab showed that loss of RNF 8 or RNF168 genes can inhibit breast and ovarian tumour development in preclinical models with BRCA mutations. They also revealed the underlying molecular mechanisms, involving the accumulation of DNA–RNA hybrids (R-loops), increased cell replication stress and genomic instability that can eventually lead to the death of BRCA-mutant cancers.
“Currently, BRCA-associated cancers are treated with different approaches, including PARP inhibitors and Platinum-based compounds. However, patients can develop resistance to these therapies, and there’s a need to come up with new treatments. Our discoveries point to novel strategies that can bring hope to those patients.”
The team also discovered a novel DNA repair mechanism that provided new insights for treating BRCA1-deficient cancers, in a collaboration with Dr. Karim Mekhail, a professor of laboratory medicine and pathobiology at the University of Toronto’s Temerty Faculty of Medicine.
They found that microtubule filaments from the cell cytoplasm can push the envelope of the cell nucleus, triggering tiny tubules to reach the DNA inside and catch most double-stranded breaks. BRCA1 mutant cells rely heavily on this mechanism to proliferate, and the team is trying to exploit this vulnerability to stop cancer growth.
Razq did not know what disease his grandmother had. His family tried to shield him from the sadness of the situation. Only years later, he learned she died of ovarian cancer.
This experience not only sparked his interest in cancer research but also in advocating for cancer awareness, especially in communities where cancer remains a taboo subject. “Times are different now—there is improvement in how we treat metastatic cancers, more knowledge of what genes are linked to cancer, and new ways to detect it,” he reflects.
“Keeping it hidden is dangerous,” he says. “Being informed can save lives.”
He remembers his grandmother’s suffering, the quiet agony behind closed doors. That memory reminds him that his work is never abstract. It is about real people, real families.
Razq recalls riding hospital elevators for work, surrounded by patients or families visiting loved ones. He recognizes the look of pain and the weight of fear. “They might be suffering because their parents or family members were at high risk of not surviving the cancer. That drives me to keep working every day.”
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.
Image-guided surgery has transformed surgical procedures by enabling minimally invasive approaches and shorter recovery times. However, surgical precision during these operations depends heavily on the ability to accurately measure distances within the body during surgery. Researchers from The Institute for Education Research at UHN evaluated the feasibility and accuracy of a digital tool that uses artificial intelligence (AI) to support more consistent and accurate surgical measurements.
The research team developed a digital ruler using computer vision technology that allows AI models to analyze surgical video footage. The model identifies the tips of surgical instruments and calculates the distance between them based on the known size of the instruments. The AI model was trained using over 1,200 annotated surgical videos and evaluated against measurements estimated by surgeons and physical rulers used in simulated surgical settings.
The results showed that the AI-based tool had less variability than human estimates, especially over longer distances. The tool performed best when used with human oversight, where manual reviews and corrections were made to help the AI correctly identify instruments.
While the tool remains a proof-of-concept, the researchers anticipate future applications in the operating room through integrating on-screen measurements in surgical video feeds. The tool could also be used after surgery to help surgeons review recorded procedures and refine measurement techniques.
Overall, this study demonstrates the potential for AI-based tools to support more objective and consistent measurement during image-guided surgery, which may help improve standardization and quality of surgical care.
Raphael Kwok, first author of the study, is a research assistant in the lab of Dr. Amin Madani.
Dr. Amin Madani, senior author of the study, is an Education Investigator at The Institute for Education Research at UHN. He is also the Director of the Surgical AI Research Academy (SARA) at UHN and an Assistant Professor in the Department of Surgery at the University of Toronto.
This work was supported by UHN Foundation and the Temerty Centre for AI Research and Education in Medicine at the University of Toronto.
Dr. Amin Madani is a consultant for Johnson & Johnson. Dr. Allan Okrainec is a consultant for Medtronics and MedTech Syndicates, holds equity interests in GT Metabolic Solutions and Qaelon Medical, and receives honoraria from Ethicon.
Kwok R, Yoshida T, Hunter J, Laplante S, Brudno M, Fecso A, Okrainec A, Madani A. Development of an artificial intelligence based virtual tool for measuring distances during image-guided surgery. Surg Endosc. Epub 2025 Dec 9. doi: 10.1007/s00464-025-12461-2.
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 Fresh Way to Treat Depression: UHN researchers see preliminary success with psilocybin for treatment-resistant depression.
● Ice: Winter’s Safety Challenge: Advanced winter footwear can help reduce slips, but extra precautions are still needed on ice.
● Harnessing AI to Decode the Heart: New, publicly available AI model to analyze data from ECGs.
● Linking Genes and Therapy Response: Gene mutation in blood-forming cells may improve cancer immunotherapy results.
Read these stories and more online here. To read previous issues, see the newsletter archive.
The UHN Mission Excellence Awards celebrate individuals and teams whose work advances clinical care, research and education in support of UHN’s mission of A Healthier World. Presented at a ceremony on January 28, the awards recognize exceptional contributions that are shaping the future of health care across the organization.
“These awards honour the dedication, ingenuity, and creativity of TeamUHN, celebrating excellence in clinical care, education, and research,” said Dr. Kevin Smith, President and CEO of UHN. “The work of this year's recipients challenges all of us to raise the bar.”
This year, the UHN Mission Excellence Awards highlighted innovation across the full continuum of health care—from scientific discovery with future therapeutic promise to solutions already improving patient safety and care delivery at scale.
Dr. Pamela Ohashi, recipient of the UHN Inventor of the Year Award (Individual), was recognized for her discovery of a novel immune receptor—the gamma delta (γδ) T-cell receptor—that may enable a new approach to cancer cell therapy. A Senior Scientist at UHN’s Princess Margaret Cancer Centre and Director of the Tumour Immunotherapy Program, Dr. Ohashi and her team identified the T-cell receptor in a patient whose tumour was eliminated, successfully cloned it, and developed a therapeutic platform now in the translational research stage. Unlike conventional T-cell therapies, this approach has the potential to be applicable across a broader patient population. Further research and evaluation are ongoing to better understand its clinical potential and pathway toward commercialization.
The UHN Inventor of the Year Award (Team) also honoured Team HALO, whose innovation has already delivered measurable impact across UHN and beyond. HALO (Human Attended Live Observation) is a two-way audiovisual monitoring system that enables trained observers to monitor patients at risk of falling in real time. Now UHN’s standard of care, HALO has reduced patient falls, prevented adverse events, and supported care teams by easing workload pressures. Its expansion to more than 30 sites across Canada reflects its scalability, safety, and relevance across diverse care settings.
Together, Dr. Ohashi’s research and Team HALO’s system-wide implementation exemplify the intent of the UHN Mission Excellence Awards—recognizing work that responsibly translates ideas into action. By supporting innovation at every stage, UHN continues to advance solutions that strengthen the health system and improve care for patients, families, and communities.
Read the story with a full list of awards and awardees here.
The UHN Inventor of the Year Award is sponsored by Commercialization at UHN and recognizes an individual or team whose invention has made a substantial commercialization impact, contributing to UHN’s mission of ‘A Healthier World’.
Chronic pain affects one in five Canadians and is a heavy burden for individuals and the health care system. Researchers at UHN’s KITE Research Institute (KITE) reviewed the impact of ECHO Pain, a chronic pain and opioid management education program for health care professionals, and identified how it has strengthened chronic pain care across Canada.
People living with chronic pain face higher health care costs, limited access to specialized care, and reduced quality of life. At the same time, the rate of opioid addiction and overdose in Canada continues to rise. Together, these challenges highlight the need for better education and support for health care providers to ensure safe and effective chronic pain management and reduce the risks associated with prescribing opioids.
To address this need, a team at UHN and Queen’s University co-developed ECHO Ontario Chronic Pain and Opioid Stewardship (ECHO Pain). This virtual, case-based health professions education program brings together a team of specialists and primary care providers to discuss real patient scenarios, share best practices, and strengthen chronic pain and opioid management skills. Between June 2014 and June 2024, the program delivered 529 sessions and engaged over 1,500 health care professionals from across Ontario, including many practising in remote communities.
Participants of ECHO Pain reported high program satisfaction and increased confidence and knowledge in both chronic pain and opioid management. When the research team evaluated prescribing patterns, ECHO-trained care providers significantly reduced opioid prescriptions compared to those who did not participate. The program also fostered a strong, interdisciplinary community where health care providers could share knowledge, skills, and resources. Its virtual format provided timely access to education for physicians working in rural, remote, and underserved communities.
The research team identified several components of the program that contributed to its success, including strong administrative support, a dedicated research and education team, and consistent engagement from the multidisciplinary program team. They also emphasized the importance of regular recruitment of participants and patient cases, and ongoing evaluation to ensure the program continues to meet the needs of health care providers.
As the program model continues to be adopted nationwide, ECHO Pain offers a promising approach to strengthening chronic pain management and equipping health care professionals with the necessary skills, resources, and community to improve care for people living with chronic pain.
Dr. Andrea Furlan, first author of the study, is a Senior Scientist at UHN’s KITE Research Institute. Dr. Furlan is also a Professor in the Department of Medicine and the Institute of Medical Science at the University of Toronto.
This work was supported by UHN Foundation, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long-Term Care, the Ontario Medical Association, and the Northern Ontario Academic Medicine Association.
Dr. Furlan has a monetized YouTube channel and receives royalties from two published books for people with chronic pain.
Furlan AD, Zhao QJ, Taenzer P, Smith AJ, Fabico R, Morgan K, Mostyn R, Flannery JF. Ten Years of ECHO Chronic Pain and Opioid Stewardship in Ontario: Impact and Future Directions. Healthcare (Basel). 2025 Dec 8. doi: 10.3390/healthcare13243203.
A recent international, multi-centre study published in JAMA Neurology, coordinated by researchers from UHN’s Krembil Brain Institute (KBI), revealed that repeated head impacts (RHI) have more far-reaching effects that previously thought.
The last few years have seen a resurgence of discourse on the long-term effects of RHI, particularly for professional athletes such as football players and boxers. RHI is associated with an increased risk of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease that can cause behavioural issues and cognitive decline.
CTE can only be diagnosed by examining the brain for CTE neuropathological change (CTE-NC) after an individual dies. CTE-NC is characterized by abnormal accumulations, called aggregates, of a misshapen form of the tau protein in neurons and astrocytes—cells that support neurons—in their brain’s cortex. However, until now, research has focused almost exclusively on the brain, overlooking another vulnerable part of the nervous system: the spinal cord.
Dr. Gabor Kovacs, a Senior Scientist at KBI, and his research team set out to address this gap by examining the effects of RHI on the spinal cord. In this postmortem study, the team analyzed brain and spinal cord tissue from 70 individuals for the presence and severity of CTE-related tau aggregates beyond the brain.
They found that individuals with CTE-NC in the brain showed significantly more frequent and severe tau aggregates in the spinal cord than those without CTE, regardless of RHI history. Notably, CTE cases also exhibited tau aggregates in spinal astrocytes, which is a feature not seen in other conditions with tau aggregates such as Alzheimer disease.
Among those with CTE, both neuronal and astrocytic tau pathology were more pronounced in individuals with a history of RHI, highlighting a cumulative effect of repeated trauma.
Age further amplified these changes with individuals over the age of 65 who had a both CTE and a history of RHI exhibiting the most severe tau aggregates. Other protein aggregates in the brain were also seen in the spinal cord, including α-synuclein, amyloid-beta, and TDP-43, which contribute to Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis, respectively. These other protein aggregates were also more common in this group—suggesting that RHI may accelerate age-related neurodegeneration and contribute to the development of other conditions beyond CTE.
“For too long, the effects of repeated impacts on the central nervous system beyond the brain have been understudied,” says first author Dr. Hidetomo Tanaka. Dr. Kovacs adds, “It is time we shift the definition of CTE to encompass not only the brain but the spinal cord as well.”
By broadening the scope of CTE research, this work deepens our understanding of trauma-related neurodegeneration and underscores the need for protective strategies to safeguard the spine as well as the brain for those at risk of RHI. Ultimately, these insights may help reduce long-term neurological burden later in life and improve quality of life for those impacted by RHI—including former professional athletes long after their sport careers have ended.
The first author of this study is Dr. Hidetomo Tanaka, a neuropathologist and a Research Fellow at the Tanz Centre for Research in Neurodegenerative Disease (CNRD) at the University of Toronto.
The senior author of this study is Dr. Gabor G. Kovacs, a Senior Scientist at UHN’s Krembil Brain Institute (KBI), a Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto, and a Principal Investigator at the Tanz CRND at the University of Toronto.
Drs. Carmela Tartaglia, a Clinician Investigator at KBI, and Charles Tator, a Senior Scientist at KBI, are co-authors of this study.
This work was supported by the National Institutes of Health (NIH), the United States Department of Defense, the Medical Research Council, and UHN Foundation.
Dr. Kovacs has a shared patent for 5G4 synuclein and a patent pending for diagnostic assays for movement disorders. He also reported royalties from Wiley, Cambridge, Taylor and Francis, as well as research support from the Rossy Family Foundation, Edmond Safra Foundation, Krembil Foundation, MSA Coalition, Michael J. Fox Foundation, Parkinson Canada, and the NIH outside of this work.
For a complete list of other authors’ conflicts, see the publication.
Tanaka H, Black LE, Forrest SL, Danics K, Sadia N, Khodadadi M, Tator C, Smith DH, Tartaglia MC, Stewart W, Kovacs GG. Spinal Cord Tau and Protein Copathologies Associated with Chronic Traumatic Encephalopathy. JAMA Neurol. 2026 Jan 26. DOI: 10.1001/jamaneurol.2025.5421.
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