On November 14th, the Krembil Research Institute at UHN hosted its inaugural Krembil Science Jam: Spotlight on Discovery, bringing cutting-edge science to life for an enthusiastic audience of approximately 120 attendees. This event showcased innovative research from 10 leading UHN scientists and clinicians, offering insights into some of the most pressing health challenges of our time.
The evening buzzed with excitement as speakers from the Krembil Brain Institute, the Schroeder Arthritis Institute, and the Donald K. Johnson Eye Institute delivered dynamic, five-minute presentations akin to TED Talks. Each presentation highlighted innovative approaches to understanding and treating diseases such as dementia, Parkinson, glaucoma, osteoarthritis, and mental illness.
Key highlights include:
● Dr. Carmela Tartaglia’s tools to detect dementia early
● Dr. Sowmya Viswanathan’s “Joint on a Chip” for osteoarthritis research
● Dr. Jeremy Sivak’s quest to tackle glaucoma at its roots
● Dr. Josh Rosenblatt inspired with a bold vision for psychedelic mental health therapies
● Dr. Olga Rojas revealed breakthroughs linking the immune system, gut, and brain
● Advancing brain research, Dr. Milad Lankarany showcased sophisticated computer models for disease study
● Dr. Luka Milosevic mapped neural circuits to illuminate Parkinson disease
● Dr. Joan Wither identified biomarkers for autoimmune diseases
● Dr. Nigil Haroon targeted novel rheumatology treatments
● Dr. Karun Singh highlighted stem cell-driven personalized therapies.
Attendees—ranging from donors and media representatives to key supporters like CAMH and Brain Canada—enjoyed an evening filled with cocktails, hors d’oeuvres, and a fun trivia game that capped off the celebration of science. A custom music playlist, complete with “walk-up” songs for each presenter, added a personal touch to the festive atmosphere.
For those who missed it, the Krembil Science Jam is available on to watch online, and you can listen to the Krembil Science Jam playlist here.
Scientists from Princess Margaret Cancer Centre have identified a new potential target for treating clear cell renal cell carcinoma (ccRCC), a kidney cancer that forms in the tubules that filter waste from blood.
This subtype of renal cell carcinoma is the most common type of kidney cancer and accounts for the majority of kidney cancer-related deaths. If detected early, surgery to remove tumours can be curative. However, for many patients, the cancer has spread by the time of diagnosis with disease reoccurrence being common after surgery.
Almost all cases of ccRCC involve the loss of an important gene called Von Hippel Lindau (VHL). Although the loss of this gene is necessary to drive tumour formation, its loss alone cannot initiate cancer. Recent studies have found that several other important genes are frequently damaged in this type of cancer. Interestingly, many of these genes are all involved in managing how DNA is packaged and controlled within cells—a process known as epigenetic regulation.
To examine this epigenetic link and find new treatment targets, the researchers screened a large library of chemical compounds, designed to interfere with various epigenetic regulators, in kidney cancer cells. One compound, called MS023, was able to reduce tumour growth. MS023 is an inhibitor of a protein known as PRMT1. This stood out as PRMT1 plays a critical role in regulating gene expression and responding to DNA damage.
Further analysis of PRMT1 in kidney cancer cells and pre-clinical models showed that it is key for cancer growth and impacts the cell cycle and DNA damage repair pathways. PRMT1 also interacts with RNA binding proteins and is important for producing messenger RNA—a key component of gene expression. When PRMT1 function is disrupted, it causes an accumulation of structures called R-loops, which, when present in excess, are abnormal formations in RNA/DNA that eventually lead to further DNA damage. As a result, cancer cells treated with MS023 become more vulnerable and struggle to survive.
These findings offer a promising new approach to treating kidney cancer, with PRMT1 emerging as a key target for future therapies. While still in the early stages, this research could pave the way for treatments that specifically target kidney cancer cells, potentially improving survival rates and offering new hope for patients.
The first author of this study is Dr. Joseph Walton, Postdoctoral Researcher at Princess Margaret Cancer Centre.
The senior author of this study is Dr. Laurie Ailles, Senior Scientist at Princess Margaret Cancer Centre. Dr. Ailles is also a Professor in the Department of Medical Biophysics at the University of Toronto.
This work was supported by the Cancer Research Society, Ontario Institute for Cancer Research, Government of Ontario, Canadian Urological Association in collaboration with Kidney Cancer Research Network of Canada (KCRNC), and The Princess Margaret Cancer Foundation.
Walton J, Ng ASN, Arevalo K, Apostoli A, Meens J, Karamboulas C, St-Germain J, Prinos P, Dmytryshyn J, Chen E, Arrowsmith CH, Raught B, Ailles L. PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma. Nat Commun. 2024 Sep 19;15(1):8232. doi: 10.1038/s41467-024-52507-y. PMID: 39300069; PMCID: PMC11413393.
The Government of Canada has announced the latest round of Canada Research Chair (CRC) funding. A total of over $182 million will support 224 new and renewed Canada Research Chairs.
Congratulations to the following UHN Researchers who received new or renewed funding from the CRC program:
● Dr. Kristin Hope, Tier 1 Canada Research Chair in Leukemic Stem Cell Biology (new). Dr. Hope is a Senior Scientist at Princess Margaret Cancer Centre and an Associate Professor in the Department of Medical Biophysics at the University of Toronto. Funding from this chair will go toward Kristin’s research on blood stem cells and the processes that lead to the development of leukemic cells and contribute to the progression of the disease. These new insights will help improve cancer detection and monitoring, and lead to novel avenues for targeting leukemic stem cells.
● Dr. Jennifer Campos, Tier 2 Canada Research Chair in Multisensory Integration and Aging (renewal). Dr. Campos is a Senior Scientist at KITE Research Institute and a Professor in the Department of Psychology and the Rehabilitation Sciences Institute at the University of Toronto. Funding from this chair will go toward investigating why older adults with hearing loss are three times more likely to fall than their peers; the use of immersive virtual reality at home to support interconnectedness between persons with dementia and their care partners; and the use of virtual reality vision training interventions to improve driving performance post-stroke.
The Canada Research Chairs Program is a national initiative to make Canada a global leader in research by investing approximately $311 million annually to support world-class researchers across disciplines. This program enhances academic excellence, competitiveness, and the training of future skilled professionals.
See here for a full list of results and here for the press release.
On October 10, 2024, the MaRS Discovery District in Toronto was abuzz with excitement as over 200 life science industry leaders, investors, and researchers gathered for the inaugural UHNLeashed Commercialization & Partnering Showcase. Hosted by Commercialization at UHN, this event showcased cutting-edge biomedical innovations and fostered meaningful partnerships aimed at transforming game-changing research into real-world medical solutions.
The showcase featured a day packed with inspiring keynote presentations, dynamic breakout sessions, and a thought-provoking panel on harnessing the power of AI and data in health care. Speakers delved into the potential of artificial intelligence, digital health, and imaging technologies to revolutionize patient care, demonstrating UHN's role at the forefront of global medical innovation.
A key highlight of the event was the public launch of UHN's Accelerator Fund, a philanthropic initiative jointly supported by the UHN Foundation and Princess Margaret Cancer Foundation, designed to bridge the funding gap in early-stage commercialization. Drs. Sarah Crome, Pamela Ohashi, and Shin Ogawa, the first recipients of the Accelerator Fund, shared their promising research and outlined how the fund would help drive their discoveries closer to clinical impact. This initiative is a testament to UHN’s dedication to supporting high-potential research and ensuring that breakthrough technologies make it to the patients who need them most.
Throughout the day, participants were treated to a series of presentations from UHN companies and new ventures, exploring investment-ready life sciences opportunities, as well as UHN's vast resources for product development partnerships. A key feature was the Partnering Café, which encouraged direct networking between researchers, investors, and industry professionals—an essential space for building partnerships to advance UHN’s health care innovations.
With its exceptional infrastructure, world-class researchers, and strong ties to industry and philanthropic partners, UHN is leading the charge in turning tomorrow’s medical breakthroughs into today’s therapies, impacting patients across Canada and around the globe.
UHNLeashed was not just an event—it was a catalyst for change, setting the stage for powerful collaborations that will drive the future of health care forward.
For a closer look at the event’s highlights, visit UHNLeashed Highlights.
“The human genome is highly complex. Every cell in our body has 6 billion letters of DNA, but only 1.5% are found in genes. The vast majority of DNA letters are found in ‘non-coding elements’ of our genome, controlling how genes are used differently across a variety of cell types in our body,” says Dr. Mathieu Lupien, recently elected Fellow of the Royal Society of Canada for his cancer epigenetics research and Chair of Genetics & Epigenetics Program at Princess Margaret Cancer Centre (PM).
To fully understand the complexity of the genome, epigenetics cannot be overlooked. Simply put, epigenetics involves the additional information on top of DNA that guides each cell in our body to use its copy of the human genome in unique ways.
“Cells can accumulate variations in the epigenetic layer, called chromatin variants, that fine-tune cell identity within an individual,” Mathieu explains.
Chromatin is the structure that packages DNA in the cell nucleus. It consists of DNA wrapped around histone proteins, forming nucleosomes. Think of chromatin like a bookshelf where the DNA is stored. Just like how tightly or loosely books are arranged can affect how easily you can access them, the structure of chromatin affects whether genes are ‘open’ or ‘closed’ to the cell’s reading machinery.When DNA is accessible in one cell type but not in another due to differences in chromatin compaction, this phenomenon is referred to as chromatin variants.
Most chromatin variants affect the non-coding regions of the genome, which harbours all the information to fine tune gene expression across each cell type in the human body. For instance, the non-coding regions include promoters, which are DNA sequences upstream of genes, act like light switches to turn genes “on” for expression. Enhancers are another example of non-coding regions found far from genes, that function like light dimmers, coordinating with promoters to adjust gene expression levels. However, how chromatin variants impact these regions of the genome to favour cancer development remains a largely unexplored and mysterious area.
DNA organization inside the cell.
Cancer can arise when chromatin variants accumulate, disrupting normal gene function and promoting uncontrolled cell growth. From Mathieu’s earliest study published in Cell, the team was the first to identify a type of chromatin variant that causes a DNA reading protein, FoxA1, to contribute to both breast cancer and prostate cancer development.
FoxA1 can recognize distinct stretches of DNA because of this type of chromatin variation, present in both cancer types. Those stretches were identified to be enhancers that regulate the gene expression specific to either breast or prostate cancer.
Mathieu moved his lab to PM in 2012 to tap into the local expertise in cancer stem cells. He collaborated with Dr. John Dick and Dr. Peter Dirks to use epigenetics to explore the underlying mechanisms of cancer renewal properties. Since then, he contributed to systematically indexing the genome of normal and cancer cells to build an encyclopedia of non-coding DNA elements across the human genome to unveil cancer-associated epigenetic variation in diverse cancer types, including blood, brain, prostate, breast and colon cancers.
“There has been a research focus on genetic mutations as a cause of cancer,” says Mathieu. “But more and more evidence is also showing how cancer can be a disease of the chromatin.”
Chromatin variant in pediatric ependymoma
Collaborating with Dr. Michael Taylor at SickKids, Mathieu’s team helped identify the first instance of a cancer type, pediatric ependymoma, arising from chromatin variants independently of genetic mutations.
Ependymoma is a type of cancer found in the nervous system and it is more frequently diagnosed in children than in adulthood. With fewer years to be exposed to carcinogens, children accumulate fewer mutations in their tumours compared to adult cancers, making it a puzzling case to understand their origins.
Tapping into the expertise of a team of epigenetics scientists including Mathieu, pediatric ependymomas were found in a study to stratify into two groups based on chromatin variants, revealing clear variations in epigenetics. Further investigation linked these patterns to environmental factors and prompted a clinical trial to test the effectiveness of epigenetic therapy, a new class of treatment options targeting chromatin variants.
Chromatin variant in triple-negative breast cancer
Studying the therapeutic resistance in breast cancer, Mathieu’s team discovered a new class of chromatin variants in chemo-resistant cancer cells, suggesting that this particular class might be treatable with epigenetic therapy.
Together with Dr. Cheryl Arrowsmith and the Structural Genomics Consortium, the team tested a series of chemical compounds in preclinical settings and showed that a specific subset of these compounds can inhibit tumour growth. Mathieu now collaborates with Dr. David Cescon, a Medical Oncologist and Clinician Scientist at PM, to determine the best way to bring epigenetic therapy into the clinic.
Mathieu was named Allan Slaight Collaborator of the Year in 2022 and has made significant strides in the field of epigenetics through his collaborative efforts.
“Collaboration is the primary source for innovation,” says Mathieu. “We innovate by merging different fields together. And by collaborating with field experts, we can avoid going blindly into a new space.”
Mathieu emphasizes the importance of strategic collaboration in academia. “Before collaborations, one needs to establish their own value proposition clearly—what you’re good at and where you need complementary expertise to accomplish what you want. Then you can engage in fruitful collaborations.”
Looking to the future, Mathieu is optimistic about the integration of epigenetics into clinical practice. “What I look forward to in the future is for the field of epigenetics to be embedded within clinical practice. Today, I’m a researcher but I am also the friend, the relative of a cancer patient. I hope that the discoveries my team is making today can inform of a new era of clinical practices.”
“It’s heading in the right direction, and hopefully, we’ll see epigenetic research transform the clinic soon.”
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 breakthrough from McEwen Stem Cell Institute has uncovered a key player in pancreatic development: immune cells known as macrophages. These cells were found to play a supportive role in the growth and development of insulin-producing beta-like cells in the pancreas.
The pancreas aids in digestion and releases hormones that regulate blood sugar. However, human pancreas development is highly complex, and little is known about how certain cell populations, including immune cells, contribute to this process. This is crucial because improper immune cell function during pancreatic fetal growth may lead to autoimmune diseases like type 1 diabetes.
While previous evidence suggests that macrophages are important for organ formation, studying this in the human pancreas has been particularly challenging.
In this study, researchers examined the developing pancreas using cutting-edge RNA sequencing techniques. They discovered a variety of hematopoietic (blood forming) cells, including two distinct types of macrophages that appear to be specifically associated with fetal pancreas development.
To explore these findings further, the team created a model using stem cells to grow mini, pancreatic-islet-like structures called organoids. These organoids contained both endocrine (hormone releasing) cells and macrophages, allowing scientists to study their interactions closely.
The results were striking—macrophages helped support the differentiation and survival of the endocrine cells and beta-like cells in particular. Additionally, when the organoids were transplanted into tissue, the presence of macrophages aided the success of the transplant.
These findings suggest that macrophages may be key players in the development of pancreatic endocrine cells, opening new doors for understanding and treating diabetes. By harnessing the power of macrophages, researchers could develop more effective strategies for engineering pancreatic tissue, offering hope for future diabetes therapies.
The first author of this study is Dr. Adriana Migliorini, Scientific Associate at McEwen Stem Cell Institute.
The senior author of this study is Dr. Cristina Nostro, Senior Scientist at McEwen Stem Cell Institute and Associate Professor in the Department of Physiology at the University of Toronto.
This work was supported by the Ontario Institute for Regenerative Medicine, the Howard Webster Foundation, the Canadian Foundation for Innovation and Ontario Research Fund, Breakthrough Type 1 Diabetes International, Canadian Institutes of Health Research, the Banting and Best Diabetes Centre, Canadian Islet Research and Training Network, Medicine by Design, Canada First Research Excellence Fund, and UHN Foundation.
Dr. Adriana Migliorini, Dr. Gordon M. Keller, Dr. Michael H. Atkins, and Dr. Cristina Nostro are co-inventors of one patent application related to this work. Dr. Cristina Nostro also has a patent licensed to Sernova Inc.
Migliorini A, Ge S, Atkins MH, Oakie A, Sambathkumar R, Kent G, Huang H, Sing A, Chua C, Gehring AJ, Keller GM, Notta F, Nostro MC. Embryonic macrophages support endocrine commitment during human pancreatic differentiation. Cell Stem Cell. 2024 Oct 10:S1934-5909(24)00325-4. doi: 10.1016/j.stem.2024.09.011. Epub ahead of print.
Every year, over 650 internationally trained clinical fellows come to UHN to advance their clinical skills and contribute their expertise to Canadian health care. However, starting medical training in a new country is often overwhelming, especially for international clinical fellows who must adjust to different health care systems, cultural norms, and communication styles.
To tackle these challenges, researchers at The Institute for Education Research at UHN developed ‘Transitions’—a specialized program designed to help internationally trained clinical fellows adapt smoothly to medical training in Canada.
The Transitions program offers a flexible blend of online modules with live virtual sessions. It covers critical topics such as navigating the Canadian health care system, effective communication, patient safety, medical ethics, and social determinants of health.
In the pilot program, 65 fellows from 11 different medical specialties participated. They reported improved learning experiences, reduced anxiety, increased confidence and a stronger sense of community with their peers.
“The success of this pilot demonstrates that tailored support can make a meaningful difference,” adds Dr. Ahmed Al-Awamer, lead author of the study and Educational Investigator at The Institute for Education Research at UHN. “This program isn’t just a bridge; it equips internationally trained clinicians with the confidence and connections they need to make an immediate impact in Canadian health care.”
Transitions is not only flexible and practical but also cost-effective, making it a solution that can be easily adopted by other institutions to support medical trainees from around the world. This year, the Transitions program has expanded and accepted around 300 international clinical fellows. The team seeks to continue improving and expanding this program.
Dr. Ahmed Al-Awamer is the lead author of the study and an Educational Investigator at The Institute for Education Research at UHN. Dr. Al-Awamer is also an Associate Professor in the Department of Family and Community Medicine at the University of Toronto (U of T) and a Scholar at The Wilson Centre for Research Education at UHN and U of T.
This work was supported by UHN Foundation, UHN International Centre of Education, and UHN Clinical Education.
Al-Awamer A, Malavade T, Jardine J, Kaya E. 'Transitions': A new pilot programme to support the transitions of new internationally educated clinical fellows. Med Educ. 2024 Nov. doi: 10.1111/medu.15523.
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