Diversity is a hallmark of life. Variation among species and cell types within a single organism is key for supporting the myriad functions and adaptations needed to survive. A new study from the Krembil Brain Institute has explored the importance of brain cell diversity for brain function and health.
“In previous studies, we found that individuals with epilepsy have lower cell diversity in a brain region that is responsible for the generation of seizures,” says Dr. Taufik Valiante, co-senior author of the study. “We also demonstrated that when neurons behave too much like one another, neuronal networks become unstable.”
“We wanted to expand on this work and understand more generally why there are so many distinct neurons within the same regions of the healthy human brain,” explains co-senior author Dr. Jérémie Lefebvre. “While scientists have previously suggested that brain cell diversity is just noise, our research into epilepsy suggested that it protects against the development of seizures.”
To explore this possibility, the team applied computational tools to model neuronal networks—complex webs of interconnected neurons.
“We applied mathematical tools that were developed in the field of ecology and have been traditionally used to study ecosystems, but rather than using them to study food webs, we used them to study neuronal networks,” explains Dr. Hutt, first author of the study. “The specific type of diversity that we explored was that related to neuron excitability—how easily a neuron will send a signal after receiving a stimulus.”
The researchers exposed their neural networks to a slowly changing signal that mimics what a neuron might experience in the environment. They found that the networks were less stable when their neurons were not diverse. This instability manifested as sudden shifts in neuron activity levels.
“Our models revealed that cellular diversity bolsters the brain’s resiliency, making it better able to maintain functions in the face of ageing, disease and injury,” says Dr. Valiante.
The team suggests that a deeper understanding of the diversity among brain cells could improve our understanding of various neuropsychiatric disorders and how to treat them.
“Our findings may explain why drugs that are used to treat epilepsy fail in so many patients. By shedding light on the underlying mechanisms of the disease, this research could pave the way for improved therapies,” says Dr. Valiante. “Importantly, changes in cell diversity are likely not limited to epilepsy, but also play a role in various neurodevelopmental and neurodegenerative conditions.”
These findings serve as a striking reminder of the fundamental role that diversity plays in the resilience of natural systems in the face of change. This truth applies not only to neural circuits but also to humans, communities and other complex systems.
This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Krembil Foundation and the UHN Foundation. Dr. Valiante is an Associate Professor in the Department of Surgery at the University of Toronto. Dr. Jérémie Lefebvre is an Associate Professor in the Department Mathematics at the University of Toronto and an Associate Professor of Biology at the University of Ottawa. Dr. Axel Hutt is Research Director at the National Institute for Research in Digital Science and Technology in France.
Hutt A, Rich S, Valiante TA, Lefebvre J. Intrinsic neural diversity quenches the dynamic volatility of neural networks. Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2218841120.
Neurons communicate with each other to form complex networks. Researchers can assess diversity within neural networks by measuring how individual cells respond to excitatory and inhibitory inputs.
When a patient is diagnosed with cancer, the family physician is often the first line of support that plays many vital roles in the patient’s care journey. However, many family physicians feel ill-prepared due to inadequate oncology education and care training, according to a recent study from The Institute for Education Research (TIER) at UHN.
Dr. Marissa Sherwood, first author on the study and a radiation oncology resident at the Princess Margaret Cancer Centre, interviewed 13 family physicians and asked them to reflect on their sense of preparation for cancer diagnosis and care, supplemental learning and previous cancer patient care experiences. Through these interviews, the researchers uncovered three main themes relating to the training needs and perceptions of the participants: lack of defined roles, inadequate oncology knowledge and education and the importance of palliative care experience.
Reflecting on the journey from diagnosis to treatment, participants expressed difficulty navigating the complex cancer care system often due to a lack of connections with specialists and other care providers. This challenge left them feeling uncertain about their roles and ability to contribute to patient care.
Participants also expressed frustration because they found that their existing medical training and knowledge of cancer care lacked relevancy and applicability in their daily practice. This disconnect can hinder a family physician’s ability to provide accurate and effective care to patients.
Further, it was revealed that a physician’s experience in palliative care was a potential opportunity for learning cancer care pathways, developing oncology skills and connecting with oncology specialists.
“As the field of cancer care continues to evolve, it’s essential that we adapt the education and support we provide to family physicians,” concludes Dr. Sherwood “By reshaping oncology education, we can empower family physicians to provide more optimal care for cancer patients and improve patient outcomes.”
This work was supported by UHN Foundation. Dr. Meredith Giuliani is an Associate Professor within the Department of Radiation Oncology at the University of Toronto and is also the Associate Dean of Postgraduate Medical Education.
Dr. Meredith Giuliani has served on ad boards at AstraZeneca and Bristol Myers Squibb. Marissa Sherwood was awarded a READS grant from the American Association of Cancer Education.
Sherwood M, Papadakos J, Kulasegaram K, Martimianakis MA, Kucharski E, Giuliani M. Exploring Family Physician Training Needs to Improve Cancer Patient Care. J Cancer Educ. 2023 Jul 14. doi: 10.1007/s13187-023-02339-z. Epub ahead of print.
UHN has appointed Dr. Bo Wang, Scientist at Toronto General Hospital Research Institute, as Chief Artificial Intelligence (AI) Scientist. Dr. Wang, whose primary research areas are machine learning, computational biology and computer vision, will take on the pioneering role that is a first for a Canadian hospital.
His appointment builds upon the launch earlier this year of UHN’s AI Hub, a UHN Collaborative Centre for AI and Data Science and another first-of-its-kind initiative in the Canadian health care landscape.
Designed to augment human intelligence through AI health care innovation, the UHN AI Hub brings together scientists and clinicians from across UHN working in AI, including those in cancer, cardiovascular disease, neuroscience, transplant and rehabilitation.
“Health care is becoming increasingly data-driven and AI plays a pivotal role in extracting valuable insights from large datasets,” says Dr. Wang, who is also co-lead of the UHN AI Hub with Dr. Shaf Keshavjee, Chief of Clinical Innovation at UHN and Director of the Toronto Lung Transplant Program.
“AI has the potential to revolutionize health care by improving patient outcomes, increasing efficiency and reducing costs,” says Dr. Wang, who has been Lead AI Scientist at UHN’s Peter Munk Cardiac Centre since 2019. “This role offers an opportunity to drive innovation and advance patient care."
Dr. Brad Wouters, UHN’s Executive Vice President of Science and Research, says Dr. Wang’s appointment “represents the long-term commitment we’re making in AI in health care at UHN and the important role it will play in achieving the organization’s goals in research, innovation and clinical care.”
Dr. Wouters says UHN is in a good position to lead this work due to the uniqueness of the vast amounts of data available here. UHN sees patients with some of the most complex cases in Canada and being located in Toronto – one of the most multicultural cities in the world – means great patient diversity.
Many UHN clinicians and researchers have already begun using forms of AI to enhance patient care. In addition to the UHN AI Hub, the Temerty Centre for AI Research and Education in Medicine at the University Toronto (U of T) is also committed to AI in health care.
“We’re well positioned to create a new leadership role like this at UHN and tap into the other expertise and investments going on in Toronto,” Dr. Wouters says. “We very much want Bo’s leadership and the new UHN AI Hub Collaborative Centre to strengthen the partnerships across Toronto, across Canada and around the world.”
Dr. Wang graduated with a PhD from the Department of Computer Science at Stanford University before he was recruited to UHN. He now holds a CIFAR AI Chair at Vector Institute and is also an inaugural Temerty Professor in AI Research and Education in Medicine, and assistant professor at U of T.
Dr. Barry Rubin, Program Medical Director of the Peter Munk Cardiac Centre, had a vision to integrate machine learning, or AI, into research, education and clinical work, and with the support of the Peter and Melanie Munk Charitable Foundation created an AI team in 2019 with Dr. Wang as Lead AI Scientist.
“For us, the secret sauce was integrating computer scientists, software engineers, data scientists and clinician researchers,” Dr. Rubin says. “From a technical point of view, they don’t speak the same language and have different areas of expertise, but we saw potential for them to be complementary.
In his new role, Dr. Wang hopes to explore some of the following AI applications:
“These are just a few examples and I’m eager to collaborate with experts across UHN to explore and implement AI solutions that improve patient care and health care operations,” Dr. Wang says.
To read more, see this story in the Canadian Press.
I am currently a postdoctoral researcher at the Princess Margaret Cancer Centre, under the guidance of Dr. Robert Kridel. Our research aims to understand the variable outcomes in lymphoma patients and develop personalized therapies through cutting-edge genomics.
Beyond research, I contribute to fostering connection, teamwork, and collaboration as the founder and chair of the UHN Postdoc Association (UHNPA).
I have been in my postdoctoral role since December 2019 and have been chair of the UHNPA since its inception in September 2021.
The goal of my academic journey has been the pursuit of knowledge and the desire to make a meaningful impact in healthcare. I completed my Honours Bachelor of Pharmacy at Monash University and continued my educational journey with an Honours Bachelor of Science and Ph.D. at the University of Melbourne and the Peter MacCallum Cancer Centre in Australia. During my Ph.D., I delved into discovery research, developing a novel 3D screening platform using the gene editing tool, CRISPR, that deepened our understanding of blood endothelial cell response to cancer therapy.
At the Princess Margaret Cancer Centre, I am immersed in pioneering treatment strategies. My postdoctoral research focuses on studying treatment resistance and defining molecular vulnerabilities in B-cell lymphoma with the goal of discovering new therapeutic targets and developing precision medicine.
Beyond the lab, I am passionate about science outreach and communications and am involved in various seminar series such as UHN STEM Talks and the UHN Summer Seminar Series. I also provide mentorship to the next generation of researchers through the UHN Summer Student Program and teaching graduate students at the University of Toronto.
I am deeply passionate about leveraging my diverse academic background to advance drug discovery and improve treatment outcomes for lymphoma patients. Witnessing the significant variability in patient outcomes has fueled my determination to develop more effective, patient-centered therapies for this complex disease.
I am equally passionate about my role at the UHNPA where I work to foster a sense of community and collaboration that enables fellow researchers to thrive, share ideas and collectively work towards advancing healthcare.
To me, health research embodies the pursuit of knowledge with a direct impact on human well-being—it is about translating scientific discoveries into tangible solutions. At UHN, I am privileged to be part of a community that shares this commitment to making a real difference in healthcare.
My work aligns closely with UHN's vision of A Healthier World by contributing to the advancement of healthcare through research and innovation. My research directly impacts patient care by aiming to provide more effective, tailored therapies, ultimately enhancing patient outcomes.
I also promote knowledge sharing and collaborations within the Ontario oncology community as a delegate in the Ontario Rising Stars in Cancer Research Network.
UHN boasts a remarkable convergence of diverse expertise, resources, and state-of-the-art facilities, creating an environment where ground-breaking research can thrive. Its strong emphasis on translational research facilitates the seamless transition from the lab to clinical applications, resulting in tangible benefits for patients.
Additionally, UHN's commitment to fostering collaboration and innovation ensures that researchers can work together across disciplines and medical programs, leading to advancements in healthcare.
The institution also supports leadership development through programs such as the Biosciences Oncology Leadership Development (BOLD) Program. This program provided me with a unique opportunity to develop self-awareness, communication and management skills in order to become a cancer leader during my postdoctoral fellowship.
This holistic approach, combining world-class research opportunities with leadership support, sets UHN apart and makes it an exceptional hub for advancing health research.
I am an avid amateur astronomer. I find solace in gazing at the night sky and exploring the mysteries of the universe. Whether it is observing celestial events, like meteor showers, or tracking the movement of planets, the vastness of space has always been a source of wonder and inspiration for me. It is a hobby that allows me to step away from the lab and connect with the cosmos in a different way.
The future of health research holds immense promise, and what excites me the most is the convergence of various scientific disciplines and technologies to drive transformative changes.
We are witnessing an era of precision medicine where treatments can be tailored to an individual's unique genetic makeup and health profile. Advances in genetic engineering, artificial intelligence and data analytics are enabling us to decode the complexities of diseases like never before. I am particularly thrilled about the potential for immunotherapies, epigenetic therapies and targeted protein degradation to revolutionize the treatment landscape for diseases like cancer, providing hope to patients who previously had limited options.
Moreover, the emphasis on patient-centric research and the growing awareness of the importance of diverse representation in clinical studies are making healthcare more equitable and accessible.
As someone deeply passionate about contributing to this progress, I am excited to be part of a dynamic and ever-evolving field that has the power to transform lives and make a lasting impact on global well-being.
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 (UHN Office365 account is required; open to UHN staff, trainees and volunteers).
Brain Canada’s Future Leaders in Canadian Brain Research program has awarded $2.8 million to support 28 early-career brain researchers this year. The Future Leaders in Canadian Brain Research program supports novel and transformative research that changes our understanding of nervous system function and dysfunction and their impact on health. This year is the largest cohort of researchers to ever receive funding since the launch of the program.
Congratulations to the following three UHN researchers who received funding for their work:
● Dr. Milad Lankarany, Scientist at the Krembil Research Institute, is developing advanced methods in computational neuroscience, engineering and neurotechnology to understand how neural systems process information, ultimately to help treat neurological disorders and improve our ability to understand complex neural activity to enhance data collection.
● Dr. Tijana Simic is an Affiliate Scientist at the KITE Research Institute. Her research focuses on understanding behavioural and neurological predictors of recovery in individuals with language deficits resulting from neurological issues like stroke or progressive aphasia.
● Dr. Naomi Visanji is an Affiliate Scientist at the Krembil Research Institute where she leads the in vivo research arm of the Rossy Program for Progressive Supranuclear Palsy and uses biospecimens and experimental models to understand the pathobiology of proteins associated with neurodegenerative disease.
This funding program was made possible through support of the Canada Brain Research Fund (CBRF), the Azrieli Foundation, The Erika Legacy Foundation, The Arrell Family Foundation, the Segal Foundation and the Canadian Institutes of Health Research.
To see the full list of grant recipients click here.
I am a postdoctoral researcher in Dr. Sonya MacParland’s lab at Toronto General Hospital Research Institute and the Ajmera Transplant Centre as well as Dr. Gary Bader’s lab at the University of Toronto's Donnelly Centre. My research focuses on using single cell genomics to study the human liver.
My research has always focused on human health. The opportunities I have had to engage with patients and positively impact their health have been incredibly motivating. At UHN, I can directly engage with clinicians and patients to understand the most pressing questions and challenges in the field.
My work contributes to the understanding of childhood liver diseases, including rare metabolic and immune disorders. We aim to shed light on the intricate cellular aspects of the pediatric liver, which has been less explored compared to adult livers. By using single-cell RNA-seq—a technology that identifies what genes are active in each cell—to examine healthy pediatric livers, we are building a crucial foundation of knowledge. This knowledge will be pivotal in comprehending the progression of pediatric liver diseases, ultimately facilitating better diagnostics and treatment options for young patients, aligning with UHN's commitment to improving global health.
The team spirit here at UHN is key to push forward our health research. I delve deep into computational biology and sometimes I can get wrapped up in the nitty-gritty details and lose sight of the broader perspective. The regular collaboration with the translational research team, clinicians, patient partners and fellow researchers keeps me grounded and helps me see the bigger picture.
I am passionate about the outdoors and thrilled to be back in Canada to spend more time out in the woods.
I think we are at an amazing point for biomedical research. The high-throughput techniques that have previously been used mainly for basic research have become much more widely available and robust. I think that we will get to see more and more of them directly used for to translational and clinical applications.
How to Participate in You @TeamUHN
You @TeamUHN is a campaign to highlight the important scientific contributions that research lab staff, trainees and learners, administrative staff, core facilities staff, Research Solutions & Services staff, and volunteers make towards A Healthier World through discovery and innovation. If you’re interested in sharing your story, we invite you to complete this form here (UHN Office365 account is required; open to UHN staff, trainees and volunteers).
This year, five UHN researchers were elected as Fellows of the Canadian Academy of Health Sciences (CAHS). Considered to be one of the highest honours for individuals in Canadian health sciences, Fellows are nominated from across all disciplines and recognized for their excellence in advancing academic health sciences.
UHN is proud to congratulate the following UHN researchers on their elections:
● Dr. Peter Backx is a Senior Scientist at the Toronto General Hospital Research Institute and his research focuses on understanding the molecular and ionic underpinnings of the heart’s electrical and contraction properties, specifically in relation to disease.
● Dr. Mojgan Hodaie is a Senior Scientist at the Krembil Research Institute where her research specializes in using advanced brain imaging and artificial intelligence tools to study chronic neuropathic pain such as trigeminal neuralgia.
● Dr. Samir Sinha is a Clinician Investigator at the Toronto General Hospital Research Institute where his research interest is in the care of older adults.
● Dr. Lillian Siu is a Senior Scientist at the Princess Margaret Cancer Centre. Her research focuses on new anticancer drug development specifically in head and neck cancers. She also leads many genomics initiatives and immuno-oncology trials at Princess Margaret.
● Dr. Michael Tymianski is a Senior Scientist at Krembil Research Institute where he studies the molecular mechanisms underlying stroke, traumatic brain injuries, chronic pain and other major health disorders.
For the full list of 2023 CAHS Fellows, read the full press release here.
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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