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Welcome to the latest issue of Research Spotlight.
As Canada’s largest research hospital, UHN is a national and international source for discovery, education, and patient care. This newsletter highlights top research advancements from over 5000 members of TeamUHN—a diverse group of trainees, staff, and principal investigators who conduct research at UHN.
Stories in this month’s issue:
● Immunoengineering the Human Heart: Researchers uncover the role of human cardiac immune cells by engineering a model of the heart.
● Managing Radiation Complications: Novel classification system changes the understanding of severe radiation complications.
● New Hope for Neurological Treatments: New study unveils a promising non-invasive technique to boost brain function and aid recovery
● Virtual Reality for Rehabilitation: Exploring the link between concussion symptoms and visual stimulation.
Read these stories and more online here. To read previous issues, see the newsletter archive.
Research from UHN’s KITE Research Institute (KITE) investigates integrating virtual reality (VR) into conflict management strategies to help reduce aggression in mental health inpatient units.
Conflict in mental health units can lead to aggressive behaviour, posing safety concerns and worsening health outcomes for patients. The Safewards model, an evidence-based framework, was developed to address issues of conflict and aggression using strategies like relaxation techniques, exposure to scented towels, and relaxing music.
VR has been previously used as a relaxation tool across various clinical settings, offering a novel strategy for addressing aggressive behaviour. When combined with sensory elements like scent, VR can help enhance relaxation and positive emotional states.
A team led by Dr. Lora Appel, a KITE Affiliate Scientist and the study’s senior author, explored how VR can be incorporated into the Safewards model to help manage aggressive behaviours in mental health inpatient units. They tested VR experiences with nurses from a mental health unit at the Michael Garron Hospital in Toronto.
Nurse participants experienced virtual reality scenes (e.g. tropical beach, forest waterfall, or mountain lake) through a head-mounted display (HMD), with corresponding sounds and scents matched to the scenes.
The study’s findings revealed that the VR intervention, especially when enhanced with scent, effectively complemented the Safewards model strategies by offering benefits such as relaxation, enjoyment, and engagement with the virtual scene. The nurse participants also provided valuable feedback on the feasibility and user experience of integrating VR into clinics.
Dr. Appel explains, “The participants emphasized the importance of maintaining a user-centric design that can adapt to different symptoms and severities of impairments. Customizability in content and delivery is essential to ensuring that these novel interventions meet the diverse needs of mental health patients.”
By integrating VR into the Safewards model, researchers aim to enhance the benefits and extend the reach of existing strategies, potentially revolutionizing how mental health units manage aggression to support both patients and staff.
This work was supported by TD Community Health Solutions and UHN Foundation.
Pardini S, Kim S, de Jesus B Jr, Lopes MKS, Leggett K, Falk TH, Smith C, Appel L. SafeVRwards: Designing a complementary virtual reality module to the Safewards framework intended to relax and manage conflict in mental health wards. BMJ Open Qual. 2024 Jun 4. doi: 10.1136/bmjoq-2024-002769.
Researchers at The Institute for Education Research (TIER) at UHN are examining how medical schools are preparing for a digital future by analyzing their strategic plans to better equip future health care professionals.
As health care becomes increasingly digitized, medical schools in Canada are preparing for significant changes in patient care. Understanding how these institutions adapt is crucial for shaping the future of health care delivery and education.
A team led by Dr. Paula Rowland, TIER Scientist and lead author of the study, analyzed 59 strategic plans from medical schools, academic health science centres, and research centers across Canada to explore how they are preparing for digital health transformation.
Their findings reveal two perspectives on digital health within medicine. The first viewpoint sees digital health as an extension of the traditional academic framework, building upon existing practices and expertise. These strategic plans emphasize how digital health can enhance clinician skills and expand research efforts.
The second perspective envisions a more transformative shift as a result of digital health care where digitization reshapes how care is delivered, what knowledge is prioritized, how patients are understood, and how data is used.
Dr. Rowland also emphasizes the importance of understanding the social impact of technological changes, “As digital health continues to evolve, its impact will extend beyond technology, reshaping education, clinical practices, and patient interactions. Our findings highlight the need for thoughtful integration of digital tools, ensuring that future health care professionals are well-equipped to navigate and lead in a rapidly changing landscape.”
Strategic plans serve as a roadmap for the desired future, highlighting specific health care challenges and mobilizing resources to integrate new technologies and practices. The successful adaptation of medical schools to this digital future will be essential in providing high-quality care and advancing medical knowledge for years to come.
This research was done in relation to a special interest group, supported by The Institute for Education Research at UHN, known as the Ethics, Technology, and Change in Healthcare Work. More information about the group can be found here.
This work was further supported by the Social Sciences and Humanities Research Council of Canada and UHN Foundation. Dr. Paula Rowland is a Wilson Centre Scientist in the Office of the Vice Dean Medical Education at the Temerty Faculty of Medicine. She is also an Associate Professor (status only) in the Department of Occupational Science and Occupational Therapy and an Associate Professor at the Institute of Health Policy, Management, and Evaluation at the University of Toronto.
Rowland P, Brydges M, Kulasegaram KM. Sociotechnical imaginaries in academic medicine strategic planning: a document analysis. Adv Health Sci Educ Theory Pract. 2024 May 27. doi: 10.1007/s10459-024-10339-x.
When patients with head and neck cancers receive radiation therapy, they may develop oral health side effects including dry mouth, infections, loss of taste, and a red and sore lining of the mouth. To help mitigate these risks, patients are screened in the Dental Oncology Department before undergoing treatment—an important part of patient care at the Princess Margaret Cancer Centre.
“We are here to make sure that oral disease does not become a complication of the cancer therapy,” says Dr. Michael Glogauer, Dentist-in-Chief at UHN.
Michael also does research on how to make the experience of cancer treatment better for patients by keeping an eye on their oral health. He does this with the help of a type of immune cell called a neutrophil.
“We found in a study that neutrophil entry into the mouth is an excellent biomarker for determining the health status of the gums and monitoring oral health during cancer therapy. The presence of neutrophils tells us when there is a shift towards a disease pattern or pathogenic process.”
Previous research from Michael’s lab, published in Blood Advances, discovered a specific subset of neutrophils in blood circulation called primed polymorphonuclear neutrophils. These primed state neutrophils arrive at sites of inflammation and fight infections quicker than other resting-state neutrophils.
Just as oral neutrophils tell us about the health of patients with head and neck cancer, these ready-to-act neutrophils in the blood are also important for patients with leukemia who are getting bone marrow transplants. Michael’s team found that these blood cells can help identify patients likely to get blood infections post bone marrow transplants.
“Over the years, there has been more appreciation for how oral health impacts systemic health. Many health services and departments are now recognizing that oral health needs to be optimized in patients with certain conditions.”
Working with Drs. Adriana Luk and Phyllis Billia from the Peter Munk Cardiac Centre at UHN, Michael’s research team discovered that oral health may have a significant impact on the survival of patients who undergo heart transplants. The Dental Oncology Department works to ensure optimal oral health for these patients, making it a comprehensive dental unit serving a diverse range of patients within the UHN.
The team also implemented the use of a portable radiograph device to conduct dental examinations and perform certain procedures directly in the cardiac unit for patients who cannot be moved. This approach helps eliminate existing oral disease before surgery.
Another exciting area Michael researches is to understand the components of a healthy oral microbiome and how it varies from person to person.
“Some patients have to work really hard to maintain good oral health. Others, on the other hand, don’t need to put in too much work,” says Michael. “We're trying to understand what leads to this phenomenon.”
The team have identified specific strains of bacteria called Streptococcus salivarius SALI-10, that are critically important in maintaining good oral health. These bacteria, found in only 1% of population who are gifted with excellent oral health and resistance to dental disease, produce a new class of antibiotic-like molecules called phosphorylated lantibiotics, which can eliminate pathogens and regulate immune cells within the oral environment.
“We want to introduce these biotherapeutic bacteria to the oral cavity of patients who have to work very hard to maintain their oral health.”
In 2019, Michael co-founded a biotechnology company called Ostia Sciences, based on his discovery of salivarius SALI-10, to develop novel probiotics for the restoration of oral health.
“One of the things I love about a career in science is that it is all about making a difference and making discoveries in things that were previously maybe underappreciated.”
When Michael was in dental school, the field of dental oncology was in its infancy and there were no courses on how cancer experience impacts oral health.
“The education system in the past didn’t expose trainee dentists to this field,” says Michael, “That’s why, with Dr. Erin Watson, we started a course in 2020 at the Faculty of Dentistry that familiarizes dental students with the field and provides them with practical experience in our clinic.”
The team also set up a one-year dental oncology fellowship program where they train dental graduates on providing dental care to patients before, during, and after cancer therapy.
“Nowadays, thanks to advancements in cancer treatment, many patients are surviving cancer and their therapy. However, the disease and treatment still impact their oral health,” says Michael, “We need dentists who are familiar with these oral complications so that they can manage the situations appropriately.”
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.
The Canadian Institutes of Health Research (CIHR) has announced the results of its Spring 2024 Project Grant funding competition. The Project Grant program is designed to support ideas that will advance health-related knowledge, research methodologies, patient care, and overall outcomes.
For this round of funding, 21 research teams at UHN were awarded nearly $19 million, spanning 20 full research grants and one priority announcement grant. Nationwide, 373 full research grants were funded for a total investment of $325 million. Additionally, 68 priority announcement grants received $7.6 million and five supplemental prizes were awarded $210,000.
Among the awarded projects at UHN are investigations into tissue engineering for cell therapy, treatments for individuals with mental illness, muscle training for patients receiving mechanical ventilation, drug tolerance in cancer, insulin signalling, chronic pain, and a myriad of other innovative studies.
Congratulations to all the awardees for their outstanding contributions to advancing health research.
Click here to see the full set of results.
A new study from Toronto General Hospital Research Institute (TGHRI) and McEwen Stem Cell Institute (McEwen) has uncovered a novel method to model the involvement of yolk sac macrophages—precursors to immune cells during embryonic development—in human heart development.
Cardiac macrophages—immune cells within the heart’s muscular tissue—originate from the yolk sac and migrate to the heart during early embryonic development. These primitive macrophages remain in the adult heart and are primarily maintained through self-renewal independent of white blood cells such as monocytes.
“The role of macrophages during cardiac development is poorly understood,” says Dr. Slava Epelman, Senior Scientist at TGHRI and co-senior author of the study. “There is evidence suggesting that these macrophages are involved in artery development and the growth of lymphatic vessels, which transport lymph throughout your body. However, this evidence is based on experimental models, not human tissue, and beyond these roles, virtually nothing is known.”
A major barrier to studying macrophages during development is the lack of access to developing human cardiac tissue. Recently, tissue models of the human heart, such as organoids—3D cellular clusters—and other engineered tissues using human pluripotent stem cells (hPSCs)—cells in the body that have the potential to become any type of cell—have been developed. However, these models have not yet been made to include macrophages.
The research team, including co-senior authors Dr. Milica Radisic, Senior Scientist at TGHRI, Dr. Gordon Keller, Director of McEwen, and Dr. Michael Laflamme, Senior Scientist at McEwen, collaborated to address this gap in the field. The team aimed to engineer primitive macrophages from stem cells to better understand cardiac macrophages, their interactions with other cardiac tissue, and their role in development and tissue function.
“Using a previously established system, we generated 3D contractile cardiac tissue composed of stem cell-derived cardiomyocytes and fibroblasts that stably integrate with stem cell-derived macrophages (hESC-macrophages),” says Homaira Hamidzada, a doctoral candidate in Dr. Epelman’s lab and first author of the study.
“We demonstrated that these hESC-macrophages enhance the electromechanical properties of developing cardiac tissue— such as the contraction and relaxation of muscle tissue— and promote heart muscle maturation.”
The team also discovered that these stem cell-derived macrophages clear out dying heart cells through a process dependent on a molecule called phosphatidylserine. This action reduces stress and cell death of cardiomyocytes, and promotes the development of a tissue that more closely resembles human fetal cardiac development, as indicated by tests of gene activity and metabolism.
This study provides the first description of cardiac macrophages during early human heart development, showing that hESC-macrophages play a crucial role in heart tissue development and function.
Furthermore, integrating macrophages into engineered human cardiac tissue leads to an improved model for human heart development, enabling more detailed studies using engineered cardiac tissue that closely replicates human tissue properties.
(L-R) Homaira Hamidzada, first author of the study; Drs. Michael Laflamme, Gordon Keller, Milica Radisic, and Slava Epelman, co-senior authors of the study.
This work was supported by the Canadian Institutes of Health Research, the Ted Rogers Centre for Heart Research, the Peter Munk Cardiac Centre, Medicine by Design, the Stem Cell Network, the National Institutes of Health and UHN Foundation.
Dr. Slava Epelman is an Associate Professor in Laboratory Medicine & Pathobiology at the University of Toronto (U of T) and the Lorretta Rogers Chair in Immunobioengineering at the Ted Rogers Centre for Heart Research. Dr. Gordon Keller is a Professor in Medical Biophysics at U of T. Dr. Milica Radisic is a Tier 1 Canada Research Chair in Organ-on-a-Chip Engineering and Professor in the Institute of Biomedical Engineering at U of T. Dr. Michael Laflamme is a Tier 1 Canada Research Chair in Cardiovascular Regenerative Medicine and a Professor in Laboratory Medicine & Pathobiology at U of T.
Co-authors Dr. Milica Radisic, Dr. Yimu Zhao, and Qinghua Wu are inventors on patents related to the Biowire II cardiac tissue cultivation and maturation protocols that are used as a main experimental system in this manuscript. Dr. Milica Radisic and Dr. Yimu Zhao receive royalty payments and annual fees for licensing of related inventions to Valo Health and receive milestone payments from Valo Health related to successful discovery and translation of molecules using the Biowire II platform.
Hamidzada, H., Pascual-Gil, S., Wu, Q. et al. Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways. Nat Cardiovasc Res 3, 567–593 (2024). https://doi.org/10.1038/s44161-024-00471-7
Welcome to the latest issue of The Krembil.
The Krembil is the official newsletter of the Krembil Research Institute (formerly the Toronto Western Research Institute). Research at Krembil is focused on finding innovative treatments and cures for chronic debilitating disorders, including arthritis and diseases of the brain and eyes.
Stories in this month’s issue include:
● Krembil Research Day 2024: Exceptional trainee and staff researchers impress at Krembil Research Day.
● Neuronto Research Symposium: Joint research event marks a milestone in uniting leading neuroscientists at UHN and SickKids.
● New to Team UHN: Alley Wilson joins the Krembil Research Institute as a Communication Specialist.
● Breakthrough in Parkinson’s Disease: Deep brain stimulation may treat Parkinson’s by reducing the buildup of alpha-synuclein.
● Uncovering Regulators of Arthritis: Study identifies key proteins driving inflammatory disease, potential therapeutic targets.
● New Models for Eye Disease: Material transfer between transplanted and host cells holds promise for vision repair.
● Building a Brain Atlas: The first molecular atlas of brain blood vessels from development to adulthood and disease.
Read these stories here.
We are working towards a communications refresh and the quarterly Krembil Newsletter will be paused. To read previous issues, see the newsletter archive.
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.
Learn more about our institutes by clicking below: