In an unprecedented milestone, three studies published simultaneously in The Lancet and Lancet Neurology by Dr. Michael Tymianski, Senior Scientist at UHN’s Krembil Brain Institute, and his team identified a breakthrough in stroke treatment. The findings suggest that nerinetide, a neuroprotective drug, may help safeguard brain tissue and improve outcomes for patients with acute ischemic stroke (AIS).
AIS occurs when a blood clot blocks the supply of oxygen-rich blood to the brain, leading to rapid death of brain cells. The longer the blockage remains, the greater the damage to brain tissue—a process known as infarction. Cell death continues and progressively affects more of tissue surrounding the area initially affected until blood flow is restored in a process called reperfusion. Current treatments focus on restoring blood flow via blood clot-dissolving drugs (called thrombolytic agents) or mechanical clot removal. However, these treatments are time-sensitive, and many patients experience delays before they receive care, leading to permanent disability or death.
For decades, researchers have sought neuroprotectants—drugs that can successfully target and reduce cell death, thereby safeguarding brain cells during the critical period between stroke onset and achieving reperfusion. While previous neuroprotectant trials have failed, nerinetide showed promise in preclinical models. Until now, its effectiveness in humans remained unclear.
Clinical Trials Put Nerinetide to the Test
Dr. Tymianski’s team conducted three large multi-centre, double-blind, randomized controlled trials—ESCAPE-NA1, ESCAPE-NEXT, and FRONTIER—to evaluate nerinetide’s efficacy in AIS patients. While previous pre-clinical studies suggested that nerinetide could reduce stroke-related brain damage, these trials, as designed, initially showed no significant improvement in all the enrolled patients who received the drug compared to placebo.
However, the researchers suspected that trial conditions may have masked nerinetide’s true potential. In re-analyzing the results, they went back to comparing how the trials were conducted with the studies that they had done initially in the laboratory before the clinical trials. They identified key differences between the studies where nerinetide succeeded and the real-world conditions of these trials:
In ESCAPE-NA1, some patients received a thrombolytic agent (blood clot-dissolving drug), which may have interfered with nerinetide’s effects.
In ESCAPE-NEXT, patients were included up to 12 hours after stroke onset, whereas the laboratory studies showed nerinetide worked best within a 3-hour window.
In FRONTIER, paramedics administered nerinetide to all patients in the ambulance before confirming stroke type. This included brain hemorrhages and conditions that mimic strokes, but the drug only acts to benefit patients with acute ischemic stroke.
Meta-Analysis Unlocks Nerinetide’s True Potential
In re-examining the data from the three trials, the Krembil team pooled the data for the patients whose circumstances matched those tested in the laboratory stroke experiments (690 patients out of the original 2,487 patients enrolled in total across all 3 trials). The results were striking: they found that there was a significant improvement in outcomes of AIS patients who received nerinetide compared to the placebo. Not only did more patients in the nerinetide group have better functional outcomes 90 days post-stroke, but there were fewer deaths in this group as well. Additionally, nerinetide slowed the progression of the strokes, resulting in less brain damage on CT and MRI scans. These findings—now published in three separate Lancet articles—strongly suggest that nerinetide can be an effective neuroprotectant if administered under the right conditions.
“Our results are encouraging,” says Dr. Michael Tymianski, Krembil Senior Scientist and lead author of the meta-analysis. "Another trial is ongoing in order to confirm our findings. We are excited by the potential drugs like nerintide have to redefine stroke care and improve outcomes for AIS patients,” he adds.
By providing a buffer against extensive and irreparable brain damage in a critical window before reperfusion, nerinetide could offer hope to stroke patients who face treatment delays. The research team hopes that these findings will serve as a cornerstone for continued research on ways to minimize disability and improve patients’ quality of life after an AIS.
Dr. Michael Hill is the first author of Hill et al., which details the results of the ESCAPE-NEXT trial. He is a Professor at the Cumming School of Medicine at the University of Calgary.
Dr. Jim Christenson is the first author of Christenson et al., details the results of the FRONTIER trial. He is a Professor in the Faculty of Medicine at the University of British Columbia.
Dr. Michael Tymianski is the first and senior author of Tymianski et al., and the senior author of Hill et al. and Christenson et al. He is a Senior Scientist at the Krembil Brain Institute, and a Professor in the Department of Surgery in the Temerty Faculty of Medicine at the University of Toronto.
This work was supported by NoNO Inc., Canadian Institutes of Health, Brain Canada, and UHN Foundation. Dr. Tymianski was a Canada Research Chair (Tier 1) in Translational Stroke Research.
Dr. Michael Hill received personal fees from SunPharma and Brainsgate, owns stock in Circle, has patents for systems and methods for assisting in decision making and triaging for acute stroke patients, and reports previous grants from NoNO Inc., Medtronic, and Boehringer-Ingelheim outside the submitted work. Dr. Jim Christenson received support from Brain Canada, NoNO Inc., and CIHR outside the submitted work. Dr. Michael Tymianski is the Chief Executive Officer for, owns stock in, and is the inventor of patents owned by NoNO Inc.
Hill MD, Goyal M, Demchuk AM, Menon BK, Field TS, Guest WC, Berrouschot J, Bormann A, Pham M, Haeusler KG, Dippel DW, van Doormaal PJ, Dorn F, Bode FJ, van Adel BA, Sahlas DJ, Swartz RH, Da Costa L, Ospel JM, McDonough RV, Ryckborst KJ, Almekhlafi MA, Heard KJ, Adams C, Garman DJ, Kohli Y, Schoon BA, Buck BH, Muto M, Zafar A, Schneider H, Grossberg JA, Yeo LLL, Tarpley JW, Psychogios MN,Coutinho JM, Limbucci N, Puetz V, Kelly ME, Campbell BCV, Poli S, Poppe AY, Shankar JJ, Chandra R, Dowlatshahi D, Lopez GA, Cirillo L, Moussaddy A, Devlin M, Garcia-Bermejo P, Mandzia JL, Skjelland M, Aamodt AH, Silver FL, Kleinig TJ, Pero G, Minnerup J, McTaggart RA, Puri AS, Chiu AHY, Reimann G, Gubitz GJ, Camden MC, Lee SK, Sauvageau E, Mundiyanapurath S, Frei DF, Choe H, Rocha M, Gralla J, Bailey P, Fischer S, Liebig T, Dimitriadis K, Gandhi D, Chapot R, Jin A, Hassan AE, van Zwam W, Maier IL, Wiesmann M, Niesen WD, Advani R, Eltoft A, Asdaghi N, Murphy C, Remonda L, Ghia D, Jansen O, Holtmannspoetter M, Hellstern V, Witt K, Fromme A, Nimjee SM, Turkel-Parella D, Michalski D, Maegerlein C, Tham CH, Tymianski M, on behalf of the ESCAPE-NEXT Investigators. Efficacy and safety of nerinetide in acute ischaemic stroke in patients undergoing endovascular thrombectomy without previous thrombolysis (ESCAPE-NEXT): a multicentre, double-blind, randomised controlled trial. Lancet. 2025 Feb 15; 405(10478): 560-570. doi: 10.1016/S0140-6736(25)00194-1.
Christenson J, Hill MD, Swartz RH, Adams C, Benavente O, Casaubon LK, Cheskes S, Ganesh A, Garman JD, Harris C, Harris DR, Heard K, Jenneson S, Kohli Y, Leroux M, Mayor-Nunez D, Medvedev G, Mehdiratta M, Morrison LJ, Ospel JM, Pennington S, Perez Y, Selchen D, Stebner A, Tallon J, Tkach A, Verbeek PR, Tymianski M. Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study. Lancet. 2025 Feb 15; 405(10478p): 571-582. doi: 10.1016/S0140-6736(25)00193-X.
Tymianski M, Hill MD, Goyal M, Christenson J, Menon BK, Adams C, heard K, Kohli Y, for the ESCAPE-NA1, ESCAPE-NEXT, and FRONTIER Investigators. Safety and efficacy of nerinetide in patients with acute ischaemic stroke enrolled in the early window: a post-hoc meta-analysis of individual patient data from three randomised trials. Lancet Neurology. 2025 Feb 13. doi: 10.1016/S1474-4422(24)00515-5.
In a landmark study published in Science, Dr. Maurizio De Pittà, Scientist at UHN’s Krembil Brain Institute, Dr. Fernando García-Moreno of the Achucarro Basque Center for Neuroscience, and their colleagues explored the long-debated evolutionary origins of the neocortex—the part of the brain responsible for complex functions such as cognition and sensory perception.
Until now researchers were uncertain whether the process forming the neocortex and similar brain structures in amniotes—organisms, like humans, that develop in amniotic fluid—was conserved, meaning it was passed down through evolution from a common ancestor.
Using an innovative approach combining brain cell (also called neurogenic), gene expression (also called transcriptional), and mathematical analyses, the team looked for commonalities in genes and the timing and location of the growth and development of the neurons in the circuits that make up structures like the neocortex (called pallial circuits). If the developmental process was conserved, these features would be the same, or homologous, across the models of different amniotes.
However, rather than similarities, the team found significant divergence instead. Analysis revealed that genes expressed by the neurons destined to be part of pallial circuits differed greatly very early on in development. Researchers also found that the timing and location of neuron development varied markedly between models. These findings challenge the theory that structures like the neocortex are conserved and instead support an alternate hypothesis: that they evolved convergently.
Using advanced mathematical models developed by Dr. De Pittà with the Krembil Computational Neuroscience Hub to further analyze their findings, the research team identified that while the developmental origins of pallial circuits in different amniotes vary, all these circuits perform very similar (or analogous) functions. Equipped with this interpretation, the researchers propose that because of the vital role of structures like the neocortex, coupled with environmental pressures (for example, available nutrition), evolution drove different developmental processes to produce the same type of circuits.
Drs. De Pittà and García-Moreno and their colleagues’ work is an important step towards understanding our evolutionary history. It not only deepens our understanding of the driving forces behind neurodevelopment but may also inspire other researchers to seek evidence to explain why and how other brain structures, or other bodily systems, evolved. Understanding how and why these systems came to be is crucial for advancing their care in the future.
Dr. Eneritz Rueda-Alaña is the first author on this study. She is a Postdoctoral researcher at The Basque Centre for Neuroscience Achucarro in Spain.
Drs. Fernando García-Moreno and Maurizio De Pittà are the senior authors on this study. Dr. García-Moreno is a Principal Investigator and Ikerbasque Research Associate Professor with the Achucarro Basque Centre for Neuroscience. Dr. De Pittà is a Scientist at the Krembil Brain Institute at UHN, Assistant Professor in Temerty Faculty of Medicine at the University of Toronto, and Affiliated Scientist at the Basque Center of Applied Mathematics.
This work was supported by the Krembil Foundation Seed Fund, the Ikerbasque – Basque Foundation for Science, EASI-GENOMICS, the Spanish Ministry of Science, Innovation, and Universities (MCIU), State Research Agency (AEI), and European Regional Development Fund (FEDER), the Séneca Foundation, the Chan-Zuckerberg Initiative, the Silicon Valley Community Foundation, the Erling-Persson Family Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Cancer Society, the Department of Industry, Tourism and Trade of the Government of the Autonomous Community of the Basque Country, the Innovation Technology Department of the Bizkaia County, and UHN Foundation.
Drs. Marco Grillo and Sergio Marco-Salas co-founded a company, Spatialist, that does data-analysis for spatial-omics.
Rueda-Alaña E, Senovilla-Ganzo R, Grillo M, Vázquez E, Marco-Salas S, Gallego-Flores T, Ordeñana-Manso A, Ftara A, Escobar L, Benguría A, Quintas A, Dopazo A, Rábano M, dM Vivanco M, Aransay AM, Garrigos D, Toval A, Ferrán JL, Nilsson M, Encinas-Pérez JM, De Pittà M, García-Moreno F. Evolutionary convergence of sensory circuits in the pallium of amniotes. Science. 2025 Feb 14; 387: eadp3411.
Osteoarthritis (OA) affects a staggering 500 million people around the world. This painful and debilitating degenerative disease occurs when cartilage in the joints wears away, with the knee being the most commonly affected joint. When standard treatments stop working, the only remaining option for those with knee OA (KOA) is knee replacement surgery (called a total knee arthroplasty, or TKA). Sadly, up to one-third of patients experience no relief from this surgery provides no relief.
In a new study from UHN’s Schroeder Arthritis Institute (Schroeder), a team led by Dr. Mohit Kapoor, Senior Scientist and co-senior author of this study, has developed the first method of successfully classifying KOA patients using multiple ‘omics domains (also known as multi-omics) to explain differences in post-TKA outcomes. Using multi-omics and artificial intelligence (AI) models, researchers were able to analyze to multiple sets (domains) of biological molecules simultaneously and investigate connections between them that could not have been in previous research, which looked only at individual domains.
The Schroeder team’s breakthrough classification method (also called a model) is composed of two novel algorithms—one using an AI-based deep-learning technique to identify subtypes of KOA patients (called endotypes) and one using machine learning (ML) to analyze differences between patients within each endotype. "Our model uncovered three novel KOA endotypes and identified key features that likely contribute to differences in patients’ responses to TKA,” remarks Dr. Divya Sharma, senior biostatistician and co-first author of this study. The study further revealed that the factors contributing to whether a patient experiences pain post-TKA are unique to each KOA endotype—as are the molecular pathways responsible for the development of this disease in the first place.
“Beyond deepening our understanding of what underlies KOA and differences in patients’ responses,” says Dr. Jason Rockel, Staff Scientist at Schroeder and co-first author of this study, “we are excited by the possibility of models like ours helping to transform how treatment decisions are made”. Predictive models could be a tool for health care providers to determine whether a particular treatment will benefit a patient before they decide to offer it. Dr. Rajiv Gandhi, Clinician Scientist and co-senior author on this study, adds, “such a tool would streamline the process of finding an effective treatment for an OA patient by eliminating the need for trial and error, ultimately preventing patients from undergoing invasive treatments with long recovery processes, like TKA, without the promise of success”.
By making their data and model publicly available, the team hopes that the greater OA research community will contribute to an even deeper understanding of this debilitating disease. While this is only the first iteration, with further refinement, a tool like the model in this study has the potential to be used in clinics and clinical trials for the KOA community and beyond.
The co-first authors on this study include:
The co-senior authors on this study are include:
This work was supported by the Canada Research Chairs Program, Tony and Shari Fell Platinum Chair in Arthritis Research, Campaign to Cure Arthritis, and UHN Foundation.
Rockel JS*, Sharma D*, Espin-Garcia O*, Hueniken K*, Sandhu A*, Pastrello C*, Sundararajan K, Potla P, Fine N, Lively SS, Perry K, Mahomed NN, Syed K, Jurisica I#, Perruccio AV#, Rampersaud YR#, Gandhi R#, Kapoor M#. Deep learning-based clustering for endotyping and post-arthroplasty response classification using knee osteoarthritis multi-omic data. Ann Rheum Dis. 2025 Feb. doi: 10.1016/j.ard.2025.01.012.
*Contributed equally as first authors.
#Contributed equally as senior authors.
In the 1980s, scientists identified MYC, a powerful protein linked to more than 50% of human cancers, contributing to tumour growth.
For nearly 30 years, Dr. Linda Penn has been at the forefront of MYC research, uncovering how cancer cells rely on this potent cancer driver—and, more importantly, how to break that reliance to develop new treatments.
Here’s what we know about MYC, and two promising strategies Penn Lab is developing to treat cancers.
“MYC can regulate several key biological activities to lock cancer cells in a state favourable for its growth,” says Dr. Penn. “It impacts cell cycle, immune response, metabolic processes, genomic instability, and cell stemness.”
“Instead of strongly regulating a select group of genes, MYC binds to 10-15% of all genes in the genome, subtly tweaking their activity, but it’s enough to tip the scales toward uncontrolled cell growth,” Dr. Penn explains. “MYC is a master orchestrator of cancer growth.”
Her lab contributed to this important insight by building a novel research tool with the PM Genomics Centre, called a CpG island microarray. This was one of the first multi-gene array technologies, developed to map MYC’s influence on genes, based on the observation that MYC recognizes GC-rich regions of the genome. The MYC-bound genes fell into broad functional categories, reinforcing the idea that MYC has a widespread influence on genes and regulates wide variety of cellular activities.
The link between MYC and cancer is well established, yet efforts to develop targeted therapies have faced persistent obstacles.
MYC is what scientists call an intrinsically disordered protein—instead of having a rigid shape like many other proteins, MYC is flexible and unstructured, like a tangle of spaghetti. This means it doesn’t have the usual “pocket” where a drug could easily bind and inhibit its function.
“We can’t block MYC directly. Our strategy is to disrupt MYC’s interactions with other proteins,” says Dr. Penn. To uncover the proteins that interact with MYC, Dr. Penn collaborated with Dr. Brian Raught, a pioneer in BioID (proximity-dependent biotinylation) at PM. Their breakthrough approach using BioID tracked MYC’s interactions inside the tumour cells in an unprecedented way—by tagging MYC with a biotin ligase, they could label all the proteins that came into close proximity with it. This technique provided a comprehensive map of MYC’s interaction network, significantly expanding the known library of proteins involved in MYC-driven cancer.
Since then, from hundreds of proteins identified, the team has been pinpointing those that have a higher significance for cancer growth and decoding their MYC interactions, such as PNUTS and TFIIF. “This is an ongoing effort that we are solving with Dr. Cheryl Arrowsmith and the Structural Genomics Consortium,” she says.
Building on these foundational studies, Dr. Penn’s lab performed high throughput screens identifying small molecules that can inhibit interactions between MYC and specific partner proteins—a fruitful collaboration with scientists at OICR and SRI. “Right now, we’re validating the inhibitor molecules in cells and refining their chemistry to make them more potent and effective.”
Despite the presence of strong cancer-drivers such as MYC, cancers cannot grow without the raw materials needed to build new cells—much like a high-performance engine revving without fuel—halted and nowhere to go.
It turns out a cellular metabolic process, called the mevalonate pathway, creates the “fuel”. This chain of biochemical reactions generates cholesterol, important for keeping cell membrane integrity and forming all types of hormones, essential for cancer cells’ growth and survival.
Penn’s team made groundbreaking contributions showing how statins, a class of cholesterol-lowering drugs, could be repurposed as potential cancer therapies. Statins block the mevalonate pathway, depriving cancer cells of needed materials and forcing the cancer’s engine to come to a stop. They showed the anti-cancer effects of statins in various cancer cell types including acute myeloid leukemia, prostate cancer, breast cancer, and multiple myeloma, in collaboration with many scientists at PM.
Early studies with Dr. Mark Minden showed statins selectively killed acute myeloid leukemia cells while sparing normal cells. Encouraged by these results, Penn’s team expanded their research to solid tumours like prostate and breast cancer.
The Penn lab found a feedback loop that can compensate and replenish the metabolic products needed for cancer growth, leading to resistance for the statin treatment. They used agents to block the statin-triggered feedback loop to achieve a better therapeutic effect.
“Our research taught us that we can ‘trick’ the cells into thinking that intracellular levels of cholesterol are still high. The agents we used structurally ‘look like’ cholesterol but they are standard-of-care drugs, like abiraterone, and block the feedback loop, so that statins’ anti-cancer effect wouldn’t be compensated, it was potentiated instead,” says Dr. Penn. “Working with Drs. Robert Hamilton and Neil Fleshner in prostate cancer studies, the team are marching forward with a clinical trial, using a combined therapy of statins and abiraterone to evaluate their anti-cancer efficacy and see how they work in prostate cancer patients.”
Similarly, statins’ anti-cancer effect and its resistance-inducing feedback loop are also present in breast cancer. Collaborating with Drs. Benjamin Haibe-Kains and David Cescon, the team conducted computational screening to find and validate several approved compounds that can potentiate the anti-breast cancer activity of statins.
“Our promissory note of working on statins is that they were already FDA and Health Canada approved, so our motivation is really to understand how they work and get them to the clinic as quickly as possible. Moving statins from the cardiac clinic where they are used to control cholesterol and now exploiting them as anti-cancer agents, we aim to benefit more patients worldwide.” Dr. Penn concludes.
Dr. Linda Penn and her current cohort of lab members.
As scientists continue to unravel MYC’s secrets, Penn’s work stands as a testament to the power of persistence in cancer research. “When I first entered this field, I thought, ‘Go big or go home,’” she recalls. “And there was nothing bigger than MYC at the time.”
Her bold approach has left a lasting impression on her students and trainees, who affectionately call her “a woman with no fear.” The phrase has even become a fixture in her office—a sign gifted to her by her trainees that serves as both a tribute to her fearless mindset and an inspiration to those who step through her door. Students turn to her for guidance as they navigate their own paths, and her deep commitment to mentorship was honoured with the 2020 Richard Hill Mentorship Award at PM.
“Everyone's scientific career is shaped by their own unique journey, and they take on different lenses to view and solve real-world problems. By empowering young scientists, we foster innovative solutions to shape a better future.”
Dr. Linda Penn played a pivotal role in establishing the Office of Research Trainees (ORT) at the University Health Network (UHN)—an initiative designed to support and empower graduate students and postdoctoral researchers as they navigate their scientific careers. What started as a small project on the side of her desk in 2011 has grown into a thriving program that now oversees over 1,200 trainees across UHN, offering them career development, mentorship, and essential training opportunities.
Today, ORT offers a diverse range of workshops, covering everything from scientific writing and presenting research to peer-to-peer training sessions on technical skills. One of ORT’s standout initiatives is career panels, which allow trainees to engage directly with professionals from fields like the pharmaceutical industry, science communication, and marketing. These interactions provide young researchers opportunities to explore non-traditional career paths, gain firsthand insights, and even establish mentorship connections that shape their professional journeys.
For Dr. Penn, ORT is not just a program—it’s a platform that empowers young scientists to take charge of their futures.
"It’s important to have a clear vision to know where you're going and what you want to achieve,” she reflects. Through ORT, Penn and her current colleagues Dr. Amanda Veri and Jordan Beck are building a supportive ecosystem where young scientists can embrace risk, push boundaries, and ultimately pave the way for the next generation of discoveries.
The Office of Research Trainees (ORT) team at UHN, from left to right: Jordan Beck, Research Trainee Coordinator; Dr. Linda Penn, ORT Director; and Dr. Amanda Veri, ORT Manager.
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.
A recent study from the Krembil Brain Institute (Krembil) at UHN uncovered unique features in the brains of people with multiple sclerosis (MS) that can be used to predict chronic pain more accurately in patients.
MS is a degenerative autoimmune disease that causes the body to destroy myelin, the protective covering of cells in the nervous system. More than 50% of people with MS live with some kind of chronic pain, such as trigeminal neuralgia (TN)—an intense shooting pain in the face and neck. Despite the prevalence of chronic pain, cognitive and motor disabilities associated with MS limit the efficacy of current pain assessment methods in people with the disease.
Previous studies have found that chronic pain causes signature changes in the brain’s grey matter—a type of tissue in the brain and spinal cord—in other diseases. Researchers propose that these changes could be used to diagnose chronic pain through brain imaging. Until now, the role of these changes (called imaging predictors) had not been explored in MS.
The team, led by Senior Scientist Dr. Mojgan Hodaie, used machine learning (ML) to analyze and compare MRI scans of the brains of MS patients with and without TN, which served as a model for chronic pain. They identified 17 grey matter structures as possible imaging predictors since these structures showed distinct differences between the groups. Remarkably, these structures were such effective predictors of chronic pain that their ML model was able to identify whether a patient had chronic pain with nearly 95% accuracy by analyzing MRI scans alone.
These findings advance our understanding of how MS and TN impact the brain and provide a way to improve chronic pain diagnosis in MS patients. Because imaging predictors are not subject to the same limitations as current assessment methods (such as reliance on self-reporting), they could make the diagnostic process more objective and accurate. This research marks an important step toward improving how chronic pain is diagnosed, managed, and ultimately, alleviated in the MS community.
The first author of this study is Dr. Timur Latypov, a Postdoctoral Researcher at The Hospital for Sick Children, and former Doctoral Candidate in the Faculty of Medicine at the University of Toronto.
The senior author on this study is Dr. Mojgan Hodaie, a Senior Scientist at the Krembil Brain Institute, Affiliate Scientist at the KITE Research Institute, and Professor in the Department of Surgery at the University of Toronto.
This work was supported by the CIFAR-Temerty Innovation Catalyst Grant, University of Toronto Centre for the Study of Pain, and UHN Foundation.
Latypov TH, Wolfensohn A, Yakubov R, Li J, Srisaikaew P, Jörgens D, Jones A, Colak E, Mikulis D, Rudzicz F, Oh J, Hodaie M. Signatures of chronic pain in multiple sclerosis: a machine learning approach to investigate trigeminal neuralgia. Pain. 2024 Dec 13. doi: 10.1097/j.pain.0000000000003497.
On February 11, we celebrate the International Day of Women and Girls in Science—a day dedicated to recognizing the extraordinary contributions of women across UHN who are advancing discovery and shaping the future of health care innovation. From game-changing researchers to dedicated postdocs, technicians, and staff, women at UHN play a critical role in driving scientific progress and fostering A Healthier World.
This year, UHN Women took a bold step in addressing gender representation in science by organizing a Wikipedia Edit-a-Thon as part of TAHSN’s Moving the Needle event. With only 20% of Wikipedia biographies dedicated to women, this initiative aimed to bridge the visibility gap by creating and updating pages that highlight the achievements of women in STEM. Thanks to our incredible volunteers, we added 20 new Wikipedia pages, ensuring that the legacies of accomplished women scientists are documented and accessible to all.
Highlights from our Wikipedia Edit-a-Thon: Thanks to our dedicated volunteers, we created and updated 20 pages, ensuring more women in science receive the recognition they deserve.
In addition to this impactful initiative, we are proud to feature the inspiring stories of six remarkable individuals—postdocs, technicians, and researchers—who are driving discovery and innovation at UHN. Their dedication, resilience, and impactful work are shaping the future of science and health care.
Join us in honouring TeamUHN's incredible women who are making an indelible mark in science.
Dr. Gabriela Melo Ghisi, Affiliate Scientist at the KITE Research Institute
Cardiovascular disease prevention and rehabilitation
The human heart beats about 100,000 times a day, pumping nearly 2,000 gallons of blood – and women’s hearts beat faster than men’s!
Growing up in Brazil, I saw firsthand the profound impact of cardiovascular diseases on underserved communities. Today, many of my patients face significant barriers to health care access. Their challenges deeply fuel my passion to bridge these gaps and bring better care to those who need it most.
The most exciting part of my work is the opportunity to develop and implement innovative patient education strategies that empower individuals to take control of their heart health. When we give people the proper tools to manage their own health—through education and resources—we help build a healthier, more resilient society.
Being a woman in science means embracing my identity to break barriers, pave the way for future generations, and contribute diverse perspectives to research. It also means advocating for gender equity in health care and research leadership and overcoming cultural and systemic challenges to create meaningful change in science and society.
We can foster inclusivity by promoting mentorship programs, ensuring equal opportunities for leadership roles, and challenging gender biases in scientific research and funding. Encouraging work-life balance and visibility of female role models in science is also crucial.
As a woman, mother, and immigrant from a low- and middle-income country, I’ve defied the odds to become a global leader in cardiovascular rehabilitation. My journey shows young women that despite challenges, they can rise and lead in any field. By sharing my story, I hope to inspire young women to believe in their potential and pursue their passions, knowing that their contributions shape the future of the world.
Dr. Patcharaporn Srisaikaew, Postdoctoral Researcher at the Krembil Research Institute
Neuroscience, aging, chronic neuropathic pain, and limbic structures
The brain is one of the hungriest organs in the body, consuming about 20% of our daily energy while making up only 2% of our body weight! Fascinating!
I am deeply driven by the potential impact scientific research can have on patient care. The knowledge that my work could improve treatments and help manage health conditions is a powerful motivator. It’s incredibly rewarding to be part of the STEM field, where research and innovation can enhance the quality of life for individuals struggling with chronic health issues. My passion lies in health care, science, and informatics, with a particular focus on advancing the well-being of older adults. I find it inspiring to contribute to a field that directly influences patient care and supports healthier, more fulfilling lives.
What excites me most about UHN is the constant opportunity to learn and solve complex problems. Every day presents new challenges, and it's fulfilling to engage with cutting-edge science. My postdoctoral work aims to help patients with trigeminal neuralgia, a debilitating pain condition, by uncovering brain abnormalities linked to cognitive function in aging and chronic pain. These insights could lead to better detection and personalized treatments, aligning with UHN's vision of creating A Healthier World.
To me, being a woman in science means changing the perception of what defines a scientist. It signifies that we are empowered women who recognize our self-worth. We have proven that women can also make significant contributions to research and innovation in STEM. I take pride in embracing both my scientific identity and my individuality. I can be kind, cheerful, and lively while still being a fun and capable scientist in STEM—proving that one can be passionate, dynamic, and impactful in STEM.
We, as women and girls in science, often encounter gender-specific barriers and challenges in our careers and professional development. I would like to take this opportunity to emphasize that fostering inclusivity and a supportive environment for women and girls in science requires us to actively support, mentor, and uplift one another. By encouraging each other and allowing everyone to learn through supportive partners and communities, we can empower ourselves. It is essential to create a safe and welcoming environment for all women and girls in STEM, ensuring equitable opportunities and promoting recognition of women in the field, which are critical steps toward meaningful progress. The International Day of Women and Girls in Science offers an important platform to celebrate achievements and drive future advancements for women and girls in the field.
I am committed to mentoring and outreach. I volunteer at UHN STEM Pathways, serve on the Outreach and Communication Committee at UHN’s Research Inclusion, Diversity, Equity, and Accessibility (IDEA), and am a member of the Krembil Trainee Affairs Committee. Additionally, I am the Career Development & Mentoring Manager for the OHBM Students and Postdocs Special Interest Group. I aim to create opportunities for aspiring students and trainees worldwide. I believe in the power of support and empowerment. I encourage the next generation of girls in STEM to embrace challenges, learn from setbacks, and keep moving forward. Together, we can redefine what’s possible. I look forward to becoming a leader who inspires future generations.
Dr. Adriana Migliorini, Scientific Associate at the McEwen Stem Cell Institute
Using human pluripotent stem cells to generate insulin-producing cells and investigating their interactions with immune cells—particularly macrophages—to advance cell replacement therapies for diabetes.
The name “macrophage” comes from a Greek word meaning “big eater,” highlighting their key role in engulfing and destroying foreign particles and dead cells through phagocytosis.
I was inspired by early mentors and my innate curiosity about how the world works, which revealed to me the transformative power of science. Their encouragement, along with the potential for meaningful impact, has driven me to pursue a career where every discovery matters. Moreover, witnessing how science can transform the treatment of chronic diseases like diabetes continues to motivate me to push the boundaries of stem cell research.
I’m most excited by the challenge of translating fundamental discoveries in stem cell biology into innovative, clinical therapies for Type 1 Diabetes. I hope my work contributes to A Healthier World by striving to develop effective cell replacement strategies that could dramatically improve the quality of life for patients living with diabetes.
Being a woman in science means contributing a unique perspective that challenges traditional boundaries and enriches the field with creativity and resilience. It’s both an honour and a responsibility to pave the way for more inclusive research environments where diverse voices drive innovation.
We can foster inclusivity by promoting mentorship opportunities, celebrating diverse achievements, and ensuring equitable access to resources and leadership roles in STEM. Building strong networks of support and encouraging open dialogue can empower more women and girls to pursue their scientific passions.
I see myself as both a mentor and a role model, eager to share my journey and the challenges I’ve overcome to demonstrate that perseverance and passion can lead to exciting scientific discoveries. Through active engagement in outreach initiatives—such as serving as a STEM pathway Ambassador for the McEwen Stem Cell Institute—I strive to empower the next generation of young women scientists to dream big and innovate boldly.
Cristiana O’Brien, Doctoral Student at the Princess Margaret Cancer Centre
Acute myeloid leukemia metabolism
Lipids in avocados have anti-leukemia effects.
During a high school field trip, I visited a conservation area where we collected water samples and observed them under a microscope. Seeing an entire ecosystem in just a few drops of water made me realize the incredible potential of microscopy. That moment sparked my interest in science and set me on the path to where I am today.
The advantage of working at a remarkable place like Princess Margaret, is getting to collaborate with different teams such as the leukemia biobank which is working to improve the prevention, diagnosis, and treatment of blood disorders by aiding research on these diseases. I am grateful to be involved in research that can contribute to a deeper understanding of acute myeloid leukemia and improve patient outcomes.
It is important for me to give back to the community through outreach, support, and celebrating peers, while also demonstrating resilience in navigating my own challenges.
In my experience, fostering mentorship and creating flexible, supportive systems are essential for providing strong foundations for the development of excellent scientists.
I would be honoured if I could inspire the same enthusiasm for science that I felt when I first looked through a microscope. Through outreach and sharing my research, I hope to spark excitement and encourage young scientists to explore opportunities in STEM.
Dr. Valeria Rac, Senior Scientist at the Toronto General Hospital Research Institute
Health Technology Assessment, Health Services and Policy Research
Marya Salomee Sklodowska Curie (my favourite scientist), was the first woman hired as a professor at the Sorbonne University in 1906. She was the first person and the only woman to win two Nobel Prizes (physics and chemistry), and she named an element ‘polonium’ after her native country, Poland.
My dad inspired me to pursue a career in science and medicine. He was a doctor of veterinary medicine and a PhD-trained scientist. When I was four years old, he used to take me to his lab at the University of Sarajevo Veterinary School every Sunday. One time, my dad let me look under the microscope, and that’s when the magic started. Every Sunday afterwards, I would eagerly get ready to go to ‘work’ with my dad to look under the microscope. I even attended my dad’s PhD defence—I was eight. My dad used to read every single paper that I wrote and would discuss my research ideas; he was my sounding board. He inspired my curiosity as a young child and instilled in me the importance of integrity, transparency, and credibility in science and research.
Being a scientist is a great privilege, and I consider myself extremely lucky that I get to do it. I get to work with a fantastic team to create new ideas and research methods for complex problems in the health care system. The most exciting part is working with people with lived experience and feeling their enthusiasm to help make things better. We work and collaborate with highly underserved patient populations and communities, and improving their care and health is the most rewarding experience.
Being a woman in science is a great and exciting career path that carries an important responsibility to create a more inclusive environment for girls and women. It means supporting other women, opening the doors for them, and creating opportunities for their leadership. We still have a long way to go. I have been blessed to work with some great women scientists and clinicians in my career who have been great mentors and sponsors, such as Drs. Cathy Whiteside, Heather Ross, and Audrey Laporte to name a few. I hope to pay it forward for the next generations.
Although some initiatives have been implemented to create a more inclusive environment, it is still challenging for women in science, particularly women and girls of colour, who face complex barriers. A multipronged approach is needed, involving the community, educational institutions, and society. Engaging girls in science at younger ages and creating opportunities for exploration is a good start. For women already in science, we must offer growth and leadership opportunities, address biases, and ensure meaningful representation in leadership roles. While some initiatives are promising, many institutions are still talking the talk without truly following through—and that must change.
I plan to continue inspiring the next generation of girls interested in STEM fields to believe in themselves and their abilities in order to build their confidence and passion to pursue these interests. Having women’s representation in STEM fields is extremely important for creating a more inclusive environment that will disrupt outdated societal biases and stereotypes. I hope that by seeing me and other women in STEM fields, the next generation will be encouraged to build their careers in STEM. By creating a strong network and a nurturing environment, we can provide support, mentorship, and a sense of belonging to the next generations of women and girls.
Dr. Suze Berkhout, Educational Investigator at The Institute for Education Research
Feminist science and technology studies
Female orcas go through menopause and orcas experience something called the "grandmother effect" where the offspring of families with grandmothers live longer. Scientists think this is because of the elder orcas’ knowledge of hunting and how they help to provide for their younger kin.
I am inspired by many of the untold stories of women in science whose profound influences we may not recognize. Some of these women include Rosalind Franklin, Katherine Johnson, Barbara McClintock, and Ursula Franklin. In particular, Ursula Franklin was the first woman to be nominated to the level of University Professor at the University of Toronto.
Experimenting with new methodologies is the most creative and exciting part of my research. My work helps us think carefully and critically about the impact of medicine and science. It invites people to understand how to be more collaborative in science and research so that more people can participate and receive the benefits of innovation.
Being a woman in science means bringing who I am and where I come from to my work. It is also about helping expand the voices and contributors to science and understanding that science is a creative and collaborative process.
If it weren't for the women who came before me, planting seeds, I wouldn't be where I am today. Those ahead must nurture the passions of future generations and create opportunities for them to act on their ideas. Additionally, we must ensure that institutions provide support for those lacking financial or emotional resources, so that individuals who may not see themselves in science and medicine are not excluded.
I am fortunate to be in a position where I can try new things that may not work and bring ideas, fields, and approaches together that have never been in conversation with one another. My hope is that someone in future will have an easier time achieving what they desire to do because I helped to clear the path.
A new study from UHN’s Toronto General Hospital Research Institute (TGHRI) found that individuals with both knee osteoarthritis (OA) and osteoporosis have distinct characteristics compared to those with only osteoarthritis.
OA is a degenerative, chronic disease that causes joint pain and stiffness, while osteoporosis is a disease that weakens bones, making them fragile and prone to fractures. Little is known about patients who have both conditions.
In the past, researchers thought OA might protect against osteoporosis and vice versa. However, studies exploring this idea have had some limitations. In addition, few studies have specifically examined knee OA disease features and pain origins in individuals with both OA and osteoporosis.
In this study, researchers analyzed whether people with both knee OA and osteoporosis form a unique group compared to those with OA alone. The team examined the prevalence of osteoporosis in a cohort of knee OA participants from the Osteoarthritis Initiative (OAI). They also evaluated subchondral bone—the layer beneath the cartilage in joints—, bone marrow lesions (painful bruising within subchondral bone), and cartilage thickness.
The results showed that at least 15% of participants with knee OA also had osteoporosis. This group exhibited lower subchondral bone density, more porous bone structure, and thinner cartilage compared to patients with only OA.
Interestingly, the researchers found that differences in cartilage were not linked to the degree of pain or symptoms in patients with both OA and osteoporosis. Instead, knee pain in these individuals was more strongly associated with bone issues. Conversely, for people without osteoporosis, cartilage changes were more closely related to symptoms.
The study suggests that osteoporosis may significantly impact knee OA symptoms for some people and that the origin of pain maybe different for these patients. Screening for osteoporosis in knee OA patients could help identify those at higher risk of bone-related pain and damage.
Dr. Andy K. O. Wong, the study’s lead author, is a Scientist at TGHRI and the Schroeder Arthritis Institute. He is also an Assistant Professor in the Epidemiology Division at the Dalla Lana School of Public Health and the Rehabilitation Sciences Institute at the University of Toronto.
This work was supported by the Arthritis Society, Canadian Institutes for Health Research, and UHN Foundation.
Wong AKO, Naraghi AM, Probyn L. Individuals with Knee Osteoarthritis and Osteoporosis Represent a Distinctive Subgroup Whose Symptoms Originate from Differences in Subchondral Bone Rather than Cartilage. Calcif Tissue Int. 2024 Dec 14;116(1):5. doi: 10.1007/s00223-024-01315-z.
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