CIHR Spring 2025 funding results for LMP faculty

Janice Robertson, University Health Network (UHN)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two closely related neurodegenerative diseases, both of which currently lack cures or effective treatments. These conditions involve progressive communication failure between neurons in the brain, a crucial function for maintaining brain health.

Understanding the reasons behind this breakdown in neuronal communication in ALS/FTD is vital for developing treatment strategies. The most common genetic cause of ALS/FTD is a mutation in a gene known as C9orf72. Our research has shown that this gene plays a key role in maintaining the brain's neuronal communication system.

Our project focuses on understanding how C9orf72 does this. By unravelling how C9orf72 helps maintain brain communication, we hope to pinpoint new treatment targets to pave the way for potential therapies for these devastating diseases.

Clinton Robbins, University Health Network (UHN)

The immune system balances defending against infections and preventing harmful inflammation. When this balance is disrupted, unchecked inflammation can cause tissue damage and disease. To restore equilibrium, the body relies on anti-inflammatory mechanisms, including regulatory plasmocytes (PCreg), which help suppress immune responses in autoimmunity, chronic infections, and cancer. However, identifying and using these cells for therapy has been challenging due to the lack of reliable markers.

Our research has identified Notch1 as a key marker of PCreg in both mice and humans. When expanded in the lab, PCreg up-regulate Notch1, highlighting its importance in their growth and function. Blocking Notch1 prevents PCreg expansion in mice and impairs their development in lab-grown human and mouse cells, suggesting it is essential for PCreg function and a potential therapeutic target.

Our project has three goals:

1. Defining the role of Notch1 in PCreg survival and function: We will determine whether Notch1 reliably marks PCreg, influences their survival and movement, and identify molecular pathways regulating human PCreg.
2. Investigating Notch1 in human PCreg generation: We will assess whether Notch1 is required for PCreg expansion, uncover how these cells suppress immune responses, and identify signals that promote their growth.
3. Testing PCreg therapy for graft-versus-host disease (GVHD): Using mouse and humanized models, we will evaluate whether Notch1+ PCreg can protect against GVHD, a life-threatening complication of bone marrow transplantation.

If successful, this research will pave the way for PCreg-based therapies in immune disorders.

Jeff Lee, University of Toronto with Co-Investigator, Jennia Michaeli, Sinai Health

Fertilization is a process where sperm and egg come together, but we still do not fully understand how it works on a molecular level, especially in humans. This lack of knowledge makes it harder to understand what causes infertility.

Our research has shown that two proteins, IZUMO1 on the sperm and JUNO on the egg, play a key role in sperm-egg attachment. These proteins, along with other recently discovered factors, likely are underlying causes of infertility. In this study, we plan to explore how sperm and egg fuse by looking at how certain molecules, like folate and zinc, might help control this process.

We will also examine clinical samples from patients who have struggled with infertility or unsuccessful in vitro fertilization to understand whether there is abnormal expression, localization and/or binding defects of IZUMO1 and other sperm fusion factors.

Finally, we aim to create new therapeutic strategies that can help improve the chances of sperm and egg successfully merging. By understanding these processes better, we hope to develop new tools to diagnose infertility and create personalized treatments, ultimately helping couples in Canada who want to have children.

Shinichiro Ogawa, University Health Network, with Co-Investigator, Boyang Zhang

Patients suffering from biliary liver diseases resulting from impaired bile flow develop severe cholangiopathies, which adversely affect cholangiocytes, the specialized cells lining the bile ducts within the liver. The progression of these cholangiopathies often culminates in end-stage liver disease, where liver transplantation remains the only viable option to extend survival.

Recent advances in human pluripotent stem cell (hPSC) research have paved the way for the development of cell-based therapies and modeling biliary disease in vitro, offering promising future alternatives for treating liver diseases. Our objective is to generate cholangiocytes from hPSCs that replicate the functional properties of normal cholangiocytes found in the human body.

This proposal aims to establish the first fully functional 3D bile duct model capable of biliary excretion, constructed from an assembly of hPSC-derived cholangiocytes. This innovative system will not only allow for a comprehensive understanding of the pathophysiology underlying cholestatic liver disease through in vitro studies but also facilitate the development of cell-based therapeutic interventions. Such interventions hold the potential to serve as alternatives to liver transplantation, offering new hope and treatment options for individuals facing the debilitating consequences of biliary liver disease.

Robert Kozak, Sunnybrook Health Sciences Centre, and Allison McGeer, Sinai Health

Respiratory viruses are a significant cause of morbidity and mortality and a burden to the healthcare system. The COVID-19 pandemic has demonstrated the potential of molecular testing and sequencing to advance our understanding of respiratory viruses. While considerable research has been done to date on influenza virus and respiratory syncytial virus, others such as parainfluenza, human metapneumovirus and the seasonal coronaviruses have not been as thoroughly characterized. This is despite the significant impact they have on the health of Canadians.

The objective of this proposal is to develop tools for identifying and characterizing non- influenza respiratory viruses in circulation in different patient groups. Additionally, we will collect real-world on transmission and infectivity in hospital settings.

Specific aims:

1. Characterize the genomic epidemiology of circulating respiratory viruses in Ontario.
2. Assess the association between viral variants and disease severity.
3. Understand transmission dynamics and infectivity in nosocomial outbreaks.

This proposal will address key questions on viral transmission and evolution as well as develop tools that can be immediately shared with the clinical community for ongoing surveillance. Additionally, it will provide valuable data that can improve hospital infection control practices and limit outbreaks.

Our group has an established record of translational research in respiratory viruses. Dr. Kozak is a clinical microbiologist and Clinician-Scientist. He has expertise in developing diagnostics assays. This proposal is being done in conjunction with TIBDN as well as collaborators at other microbiology laboratories to facilitate easy collection of patient samples. Collectively, the findings from this project have potential to better prepare Canada for future respiratory virus epidemics.

Rebecca Gladdy, Sinai Health (Department of Surgery) with Co-Investigator Adam Shlien, SickKids

Leiomyosarcoma (LMS) is a common type of adult sarcoma that arises from smooth muscle, which is only cured by surgery. Unfortunately, 50% of patients do not survive as they develop metastasis or spread of the cancer from the original site of LMS, as standard drug therapy is largely ineffective. Furthermore, we currently find it hard to define who has early LMS or not, especially in women with uterine smooth muscle tumors, which often results in under treatment.

In previous work from our LMS team, we found 3 subgroups of this cancer that have different outcomes. Also, we identified and are testing at least two new promising drug combinations based a genetic signature seen in the majority of patients. Finally, we have assembled a cohort of patients with benign or non-cancerous smooth muscle tumors that will be compared with LMS to define how to diagnose early LMS more effectively.

Thus, in this 5 year proposal we have 3 study goals:

1. To work on markers that can be used to separate the main groups of LMS that we have previously uncovered. This will include testing tumors from other sarcoma centers that have detailed patient outcomes. We will use standard laboratory and pathology techniques to separate these groupings, which then can be used to define good vs. worrisome patient groups for treatment.
2. We will work on the challenge of is a smooth muscle tumor cancer or not? To do this, we have a well archived collection of patient tissues and outcomes, from which we have begun to understand the early stages of this tumor. This will aid in deciding who needs aggressive treatment or not.
3. Our lab has generated at least two new drug combinations - standard chemotherapy plus a targeted agent for patients with LMS.

We will further work on markers to define why some patients/which subgroups respond to these combinations vs not, using our comprehensive LMS cell lines, mouse models and patient tissues. This information will aid in clinical trial development.

Mansoor Husain (Department of Medicine), University Health Network (UHN)

Heart failure (HF) is a leading cause of death and disability in people with high blood pressure, coronary artery disease, and diabetes. With aging populations, and global increases in obesity and diabetes, the incidence and health system burdens of HF are of pandemic proportions. As such, new ways of preventing and treating HF are needed.

Years of research have led to an emerging concept that HF is not just a problem of heart function, but of how the heart meets its energy needs. While healthy hearts use a variety of fuel sources, failing hearts cannot. Failing hearts have reduced capacity to generate energy, which may contribute to their inefficient pump function. This energy crisis may be due to changes in fuel supply or by a reduced ability to use certain fuels.

We have identified mitochondrial trifunctional protein [MTP], a key enzyme controlling fat breakdown, as a possible culprit in altering fuel sources available in HF. We will study the role of MTP in different types of mouse models of human HF, including HF after heart attack, after pressure overload, and HF caused by obesity and high blood pressure. We will also test if MTP can be targeted to prevent and treat different types and stages of HF.

First, we will cause HF in mice by blocking a coronary artery and causing heart attack, or blocking the aorta to increase pressure load on the heart, and by feeding mice a high fat diet and a drug that causes high blood pressure, to create the common obesity and high blood pressure-form of HF. We will then examine MTP expression- and enzyme activity in the hearts of these mice. Next, we will use genetically modified mice which allow for the deletion of MTP in heart muscle and blood vessel cells to see if this helps or harms HF. We will then examine function and metabolism of isolated hearts and heart tissues BEFORE and AFTER establishing HF. Finally, we will test if blocking MTP by GLP-1(28-36), a known inhibitor of MTP, can prevent or treat HF in our mice.

Jennie Johnstone (Department of Medicine), Sinai Health

BALANCE+: A Platform Trial for Gram Negative Bloodstream Infections with Principal investigators Nick Daneman, Robert Fowler, Todd Lee, Derek MacFadden, Emily McDonald, Sean Ong, Ruxandra Pinto, Benjamin Rogers

Bloodstream infections are a leading cause of death in Canada and worldwide, yet remain understudied, such that we do not know the best treatment strategies to be sure to cure the infection while minimizing harms of excess antibiotics causing antimicrobial resistance. Our Canadian Institutes of Health Research funded Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) Randomized Controlled Trial was the largest ever trial among patients with bloodstream infection, enrolling over 3600 patients across 74 sites in 7 countries. BALANCE confirmed that 7 days of antibiotics was as effective as 14 days, and set the paradigm for treatment duration. However, many crucial questions remain. BALANCE+ provides a platform to efficiently answer multiple next questions that are important for patients with the most common kind of bloodstream infections. All hospitalized adult patients with the most common kind of bloodstream infections - caused by "Gram negative" bacteria - will be eligible to participate. At launch this trial is addressing whether to repeat a blood culture to document clearance of infection, whether or not to 'de-escalate' (going from a broad to more specific antibiotic), the best oral antibiotics to use when switching from intravenous treatment, whether to replace or retain intravenous catheters, and specific antibiotic selection for a difficult to treat group ('AmpC') of pathogens. As each question is answered, optimal therapies will be adopted into usual care, and new questions will be introduced into the platform of the trial. In this proposal we ask for continuation funding to complete ongoing questions, and to add a new antibiotic duration question informed by BALANCE. The evidence generated by BALANCE+ will improve cure for this vulnerable patient population while decreasing potential harms from using too many antibiotics for too long.

Randomised Arthroplasty infection worldwide Multidomain Adaptive Platform trial (ROADMAP) with Principal investigators Christopher Kandel, Nick Daneman, Joshua Davis, James Howard, Todd Lee, Derek MacFadden, Tom Snelling, Jesse Wolfstadt

Hip and knee joint replacements are the most common operations in Canada with over 120,000 performed annually. A dreaded complication is a deep infection of the joint that occurs in nearly 2%, a rate that has not changed over the past 15 years. As the Canadian population ages, joint replacements are occurring more frequently, resulting in a rise in the numbers of individuals suffering from a joint infection. Treating a prosthetic joint infection requires an operation together with extended courses of antibiotics and with treatment success varying between 40-90%, there is a need to improve. ROADMAP, an international randomized control trial, is seeking to determine the optimal surgical and antibiotic interventions for prosthetic hip or knee joint infections. ROADMAP is an adaptive platform trial, which is a study design that allows for multiple interventions to be evaluated at the same time and can continue indefinitely as additional comparisons can be added once the answer to an existing question is reached. The initial surgical arm of ROADMAP will compare joint removal versus joint retention for acute infection. The initial antibiotic duration arm will compare the duration of antibiotics when the infected joint is either removed and replaced in one operation or following the second operation when the infected joint is removed and replaced over two operations. The antibiotic choice arm will evaluate whether the combination of rifampin, an antibiotic, added to the antibiotic regimen is beneficial when the joint infection is caused by certain bacteria. The platform trial design of ROADMAP will allow for efficient generation of results, ensuring that individuals with a prosthetic joint infection receive the best care. ROADMAP will provide practice-changing evidence for prosthetic joint infections and improve the research infrastructure in Canada that will allow for continual evaluation of treatment strategies to constantly improve patient-oriented outcomes.

Stephen Juvet (Department of Medicine) University Health Network (UHN) with Principal Investigators Shaf Keshavjee and Bowen Li

Lung transplantation is the only treatment option for patients with end-stage lung disease. However, the transplanted donor lung is at a constant risk of inflammation, which can lead to organ rejection. Current post-transplant care involves lifelong treatment to suppress the recipient's immune system and prevent this outcome, but negative side effects require a new approach.

At University Health Network (UHN), we are leaders in bringing research breakthroughs to the patient bedside. Our team pioneered a breakthrough technology called the Toronto Ex Vivo Lung Perfusion (EVLP) System, where donor lungs are preserved at normal body temperature (37°C) and provided oxygen, nutrients and other critical needs before transplantation. This enables donor lungs to "breathe" outside of the body for up to 12 hours. With EVLP, transplant teams can make sure that the lung is acceptable for a life-saving transplant. During EVLP, the surgeon can also apply therapies to the donor lung to improve the immune response.

EVLP has resulted in up to a 100% increase in lung transplants performed and lives saved worldwide. Despite this success, recipients who receive a lung transplant still only live an average of 6.7 years, partly due to the risk of a damaging immune response that can lead to organ rejection. To address this issue, we will develop a way to safely deliver a powerful gene editor, called CRISPR-Cas9, to donor lungs and genetically improve the immune response in the organ.

With prior CIHR support, we were the first in the world to achieve genome editing human donor lungs on EVLP. Our goal for the next phase in lung transplantation will aim even higher-donor organs with a "built-in" ability to regulate the immune response. By creating longer-lasting organs, we will significantly extend recipient survival.

Our project strongly reflects CIHR's goal to translate research into new procedures that increase the quality of life of those in need across Canada and worldwide. 

Mohit Kapoor, University Health Network (UHN) (Department of Surgery) with Principal Investigators Thomas Koch, Judith Koenig, Raja Rampersaud

Osteoarthritis (OA) is a progressive, destructive disease of the joints affecting over 500 million people worldwide. OA primary causes pain and stiffness, reducing the quality of life of those afflicted.

Currently, available treatments only mask pain, but do not stop the disease from progressing. Ultimately, joint replacement surgery is necessary to alleviate pain and improve physical activity of those with OA. Thus, development of new therapies that can both reduce OA symptoms, primarily pain, and limit disease-associated joint changes is vital moving forward.

Based on our previously funded CIHR grant, our work to date has discovered that a molecule known as miR-181a-5p is involved in cartilage and joint destruction during OA. We have also generated a therapy to block the activity of microRNA-181a-5p. In small animal models of OA, we showed that this microRNA blocker therapy can reduce cartilage and joint destruction during OA. Subsequently, we also tested the microRNA-181a-5p blocker in a large horse model, finding that injection of the blocker into horse joints showed preliminary evidence of its safety.

For this proposal, we aim to further explore the safety and therapeutic potential of the microRNA-181a-5p blocker in two horse models of OA; specifically,

1. a horse model of inflammatory pain, and
2. a horse model of joint tissue pathology.

We also propose to evaluate the safety and effectiveness of the blocker in publicly-owned horses with naturally occurring OA. We anticipate that if the proposed studies find the microRNA-181 blocker is safe and effective at reducing pain and attenuating the joint pathologies as part of OA, we will subsequently apply for human phase I clinical trials to determine the safety of the blocker in OA patients.

Christopher Licht (Department of Paediatrics), SickKids

Glomerulopathies are diseases that affect the kidneys' filtering system and often result in kidney failure, which may require treatments such as dialysis or kidney transplant. Current treatments for these conditions are not very effective, leading to poor patient outcomes and increasing health problems and healthcare costs worldwide. One specific type of glomerulopathy is C3 glomerulopathy (C3G), which can affect individuals of any age. This disease causes protein leakage in the urine and progressive kidney damage, eventually leading to kidney failure. Even after a kidney transplant, C3G often recurs causing the newly transplanted kidney to fail.

The disease is associated with an overactive immune system component known as "complement". Although new treatments targeting "complement" show some promise, they don't completely stop or cure the disease, indicating a need for better treatment options.

Our research has shown that specific white blood cells called neutrophils, which fight infections, may play a significant role in C3G. We found that these cells can undergo a particular form of activation, leading to the formation of fishing net-like structures known as neutrophil extracellular traps (NETs) in the kidneys, which may worsen the damage. The aim of our research is to understand how neutrophils and NETs contribute to kidney injury in C3G. We will use neutrophils, blood, and kidney tissue from C3G patients and lab animals (mice) to study how neutrophils are attracted to the kidneys, and how they get activated to damage kidney tissue, and explore new methods to remove neutrophils and NETs in mice to determine if this improves protein levels in the urine and enhances kidney function.

Our goal is to advance our understanding of C3G and with that pave the way towards better treatments for patients with C3G and similar kidney diseases.

Mario Ostrowski (Department of Medicine), Unity Health Toronto

Antiretroviral therapy treatment (ART) has greatly prevented the clinical progression outcome of HIV infection by suppressing plasma virus levels to below the detection limit. However, ART does not cure because it does not eliminate the persistence of a small pool of infected CD4+ T cells (also known as latent reservoir) that harbour replication competent virus that can persist indefinitely in people living with HIV (PLWH)- leading to viral rebound when treatment is interrupted. The main immune cell that can kill HIV infected cells is called the cytotoxic CD8+ T cell or CTL. PLWH usually have low functionality of their CTLs, for various reasons. However, there are a few PLWH, called elite controllers who have such potent CTLs that they force the virus into a deeply latent state.

We propose that if we can induce a similar 'state' in other PLWH, this would be a functional cure that would not require ARTs- a key step in helping eradicate HIV reservoir. Our study will use a state of the art techniques to determine whether we can make CTLs taken from PLWH, reduce or eradicate the reservoirs in the laboratory.

Laura Rosella (Dalla Lana School of Public Health)

Modelling patterns of illness to inform provincial healthcare capacity planning 

This research project aims to develop a new approach to forecast the future burden of chronic diseases on provincial healthcare systems in Canada. Accurate long-term projections are desperately needed to plan and allocate resources effectively to ensure our healthcare system can address the expected burden of chronic diseases and mitigate disparities. The project intends to utilize comprehensive population health data, epidemiological modelling, and demographic projections to estimate the prevalence of major illnesses, life expectancy, and years lived with major illness over the next 20 years. The objectives of the project include developing a forecasting model for chronic conditions, analyzing how health projections vary across social and demographic groups, and creating a decision-making tool to inform healthcare capacity planning. The approach involves leveraging linked health administrative data, validated algorithms, and survey data to assess chronic diseases and behavioural risk factors. Expert consultation and collaboration with health system leaders and a patient advisory group in two provinces will ensure the credibility and relevance of the findings to health system planning. The research findings will provide valuable insights for healthcare planning and policy-making, enabling informed recommendations for current and future healthcare needs, community-based care, and prevention efforts to address the growing burden of chronic diseases.

Bridging the Gap: Implementing and evaluating equity metrics to advance health system improvement

Over the past century, overall health has improved, but these benefits have not been shared equally. Many communities face unfair differences in health due to factors like income, race, and access to care. These differences, known as health inequities, remain a growing concern in Canada and worldwide. While health organizations recognize the need to address inequities, translating this awareness into meaningful action has been challenging. One way to drive change is by using metrics to measure and track health inequities, providing clear data to inform better decisions. Trillium Health Partners (THP), Canada's largest community hospital, has developed the Health System Inequity Metric (HSIM) to identify and monitor inequities in hospital services.

This project will

1. assess the needs of healthcare organizations,
2. support them in using the HSIM, and
3. evaluate the early effectiveness of the HSIM across different settings.

Healthcare organizations across Canada serve diverse populations with unique challenges, and a one-size-fits-all approach won't work. Our project will help hospitals and health systems integrate HSIM into their daily operations, ensuring they can effectively measure inequities, interpret the data, and use it to guide improvements. We will also ensure HSIM is adaptable so that different organizations can use it in ways that make sense for their specific communities. Currently, there is no consistent approach for measuring and reporting on health inequities in Canadian healthcare, and little evidence exists on what works best. This gap prevents progress in reducing health disparities that have been growing over time. This project will generate the knowledge needed to help healthcare systems become more equitable and effective, ensuring that all communities receive the care they need.
 

James Rutka, SickKids (Department of Surgery) with Co-Investigator Cynthia Hawkins, SickKids

Diffuse intrinsic pontine glioma (DIPG) is a devastating tumour that affects children aged 5 - 7 years and is universally fatal. The tumour's location within the brainstem prevents surgical removal, as this region controls essential functions like breathing and heart rate. Additionally, a blood-brain barrier (BBB) acts as a cellular shield, protecting the brain from toxins, pathogens and drugs in the circulation. Consequently, chemotherapies fail because drugs cannot cross the BBB to reach the tumour.

Previously, we successfully demonstrated the safety of using MR-guided focused ultrasound (MRgFUS) to temporarily open the BBB, creating an opportunity for administering cancer treatment. Excitingly, Health Canada approved our Phase I clinical trial testing MRgFUS-enhanced delivery of the BBB-excluded chemotherapy drug doxorubicin in patients with DIPG. Furthermore, our clinical team now routinely performs robot-assisted brainstem biopsies of DIPG tumours, enabling us to characterize genetic and molecular pathway alterations and design tumour biology-based precision therapy regimens.

While we investigate the use of doxorubicin to treat human DIPG using MRgFUS, we aim to expand our studies to combinatorial strategies. This can only be achieved by testing novel treatment approaches in preclinical mouse models.

We will use our genetically engineered DIPG mouse model, which mirrors the tumour's key mutations and maintains an immune system, providing a more accurate representation of the human disease. We will refine the MRgFUS procedure in this model to ensure it increases drug delivery and stimulates the body's immune defences within the tumour. We will develop a combination strategy that targets DIPG tumours by integrating molecular insights from patient biopsies with MRgFUS-enhanced delivery of targeted agents and immunotherapies, allowing us to identify the most effective combinations to achieve the most durable anti-cancer response and inform future clinical trials.

John Snelgrove, Sinai Health (Department of Obstetrics & Gynaecology) with Principal Investigator Kelsey McLaughlin

When a person is pregnant, there are many changes to their heart and blood vessels. These changes help the baby grow and develop. Sometimes there are problems with these heart and blood vessels changes during pregnancy, leading to a disease called preeclampsia. Pregnant people with preeclampsia develop high blood pressure and have damage to their organs, including the heart, kidneys, and brain.

Preeclampsia is also very dangerous for the developing baby. Preeclampsia can cause babies to be born smaller or not survive. Preeclampsia can cause lasting damage to the pregnant patient. This disease increases the risk of being diagnosed with, and dying from, heart and blood vessels disorders later in life.

In Canada, 5 in 100 people are diagnosed with preeclampsia during pregnancy. The only way to prevent preeclampsia is for pregnant people to take a drug called aspirin starting before 16 weeks of pregnancy. Aspirin is safe for pregnant people to take, not expensive, and easily available. However, very few pregnant people in Canada take aspirin during pregnancy to prevent preeclampsia. Currently, pregnant patients wait for a doctor to tell them to start taking aspirin.

We want to explore aspirin use for all pregnant people in Canada in a way that reduces any associated safety risks. This trial will explore starting all pregnant patients on aspirin by 16 weeks of pregnancy. A blood test in the late second/early third trimester will tell us a patient's risk for developing preeclampsia. If this blood test shows that the risk of developing preeclampsia is low, patients will be randomized to either continue aspirin or switch to a placebo. Patients will take their medication until 36 weeks of pregnancy. This trial will determine if patients at low-risk of preeclampsia can stop taking aspirin for preeclampsia prevention in the late second/early third trimester. This research has the potential to improve the health and quality of life of pregnant people in Canada.

Amol Verma, Unity Health Toronto (Department of Medicine) with Principal Investigators Janet Smylie, Cheryllee Bourgeois, Monica Cyr, Della Herrera, Constance McKnight, Nicole Muir, Fahad Razak, Todd Ross, Michael Rotondi, Stephanie Sinclair, Leona Star

Most First Nations, Inuit, and Metis (FNIM) peoples live in urban areas. Our relatives in cities are hidden in, or excluded from, the health information systems that are used to plan and track health and public health services. These failures drive persistent health inequities for First Peoples as there is no way to accurately understand unmet health needs nor whether existing services are helping address these gaps.

For 15 years, the Well Living House research team has worked in partnership with Indigenous health centres in seven Canadian cities to address these issues. Together we have created the largest by community, for community urban Indigenous health information dataset in Canada, known as Our Health Counts (OHC). This research project will support the continuation and progression of this work.

Specifically, it will support:

1. The creation of an Indigenous Knowledge Trust to govern, manage, and optimize OHC datasets, linked tools and resources;
2. The ongoing production of otherwise unavailable health information to address data gaps in Indigenous community defined key priority areas (i.e., emergency room use and real-time hospitalization; infectious disease rates; mental health and substance use outcomes over time) through linkage of OHC data to provincial data holdings, and linkage of patient rosters and selected EMR data to GEMINI holdings;
3. Facilitated sharing of the new health information with: a. health care providers and Indigenous community at the Indigenous health centres using customized data dashboards and b. key policy makers and their networks via quarterly knowledge-to-policy forums;
4. Growth of the FNIM health sciences workforce by supporting the first cohort of FNIM graduates from the Indigenist Epidemiology and Data Science Certificate program, composed of Indigenous data science coursework and a tailored immersive work placement within an Indigenous health centre.