CIHR Spring 2026 funding results for LMP faculty

Arinjay Banerjee, Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan

Bats represent an intriguing model to study zoonotic virus-reservoir host interactions given their apparent asymptomatic co-existence with numerous zoonotic viruses, including coronaviruses that cause severe disease in humans. However, little is known about the mechanisms that enable viral tolerance in these bats and factors that promote virus replication and shedding to cause outbreaks.

To address these gaps in our knowledge about the immunological control of virus persistence in bats, we aim to:

1. characterize virus-host interactions in bat cells and in vivo. Our long-term objective is to investigate innate and intrinsic antiviral responses in bats and their role in viral persistence. Specifically, the proposed study will characterize the persistence of coronavirus in vitro and in vivo in big brown bats (Eptesicus fuscus). A combination of viral and host directed molecular assays will be performed to determine virus persistence and replication, and the associated host antiviral response.
2. analyze longitudinal samples from temperate Eptesicus bats in North and Central America to determine immune markers of stress and viral shedding in wild-caught bats in the field. Data from wild-caught bats will be analyzed to identify immune proteins associated with increased viral shedding.
3. mechanistically characterize serum immune markers that are postulated to impact viral shedding, such as cortisol, in vitro and in vivo using bat models.

This research is significant because our approach will lead to a better understanding of factors that influence viral shedding and emergence of zoonotic outbreaks and pandemics. Our approach and study design will be extensible to other zoonotic reservoir hosts like rodents that carry multiple high consequence human pathogens.

Data from our study will inform public health and wildlife management policies to prevent future zoonotic outbreaks in humans and agricultural animals.

Venkata Duvvuri - Public Health Ontario, Vanessa Allen - Mount Sinai Hospital: Sinai Health, Thomas Braukmann - Public Health Ontario, Samir Patel - Public Health Ontario and Vanessa Tran - Public Health Ontario (with colleagues Francois Cholette, Sharmistha Mishra and Aida Sivro)

Syphilis, a sexually transmitted infection once thought to be under control, is rising again in Ontario and across Canada. Public health officials are seeing more cases each year, wider spread across communities, and a troubling increase in babies born with syphilis, a serious but preventable condition. These trends have raised urgent questions about how syphilis is spreading and whether current tools are sufficient to track and control it.

One challenge is that syphilis is difficult to monitor. Current surveillance depends mostly on case reports and basic laboratory tests, which offer limited insight into how infections are connected or how outbreaks develop.

The bacterium that causes syphilis is also hard to grow in the laboratory, making it difficult to directly test whether antibiotics remain effective. As a result, public health agencies often lack timely, detailed information needed to guide response and prevention efforts.

New scientific tools are beginning to change how syphilis can be tracked and understood. Advances in genomic sequencing make it possible to compare the genetic fingerprints of syphilis bacteria and better understand how infections spread. This project will bring these tools into routine public health practice in Ontario.

Using syphilis specimens already collected by Public Health Ontario, the research team will use genomics to detect outbreaks earlier, test how well current treatments work, and combine these findings into practical tools such as alerts and dashboards for public health and clinical decision-makers. By modernizing how syphilis is tracked and understood, this work aims to support response, better prevention, and improved health outcomes, especially for communities most affected by this infection.

Heyu Ni, St. Michael’s Hospital: Unity Health Toronto

Heart attack and stroke are the leading causes of mortality and morbidity worldwide. The most common cause of these diseases is atherosclerosis, which is when inflammation leads to cellular (leukocytes/macrophages) build up in the blood vessel, lipid (fat) deposition, and transformation of these cells into very fatty cells in the vessel wall. Platelets, which are a group of blood cells that usually help us stop bleeding, are also involved in atherosclerosis.

Atherosclerotic build-up (lesions) may decrease the blood supply, rupture, and initiate platelet adhesion and aggregation, which leads to thrombosis (vessel blockage by platelets; occlusion). Vessel occlusion can occur in critical vessels, like in the heart and brain, and results in heart attack and stroke, respectively.

We are interested in determining how to prevent or slow down atherosclerosis and how to control thrombosis - challenges both for scientists and clinicians alike. We recently found that apolipoprotein A-IV (apoA-IV), a lipid-binding protein in the blood, is a new binding protein for a major platelet receptor GPIIbIIIa. We are the first lab to demonstrate that apoA-IV inhibits platelet function and thrombosis.

In the proposed studies, we will continue our previous work and study how apoA-IV affects platelet function and thrombosis, and address whether the anti-inflammatory and anti-atherosclerotic effects of this protein are due to apoA-IV binding to platelets (via GPIIbIIIa) and whether apoA-IV affects stroke.

Our study will not only provide information regarding whether apoA-IV can be used as an antithrombotic/stroke drug but also explore the mechanisms of how apoA-IV inhibits inflammation and atherosclerosis. Since apoA-IV production is markedly increased during lipid (particularly unsaturated fat) absorption in the gut after we eat, our study may be also able to provide new guidance for food consumption in order to prevent heart attack and stroke.

Kelsie Thu, St. Michael’s Hospital: Unity Health Toronto

Lung cancer is a deadly disease and new treatments are needed to improve patient outcomes. Lung cancers use specific biological mechanisms to promote their growth and survival. One of these mechanisms, called immune escape, involves cancer cells actively turning off immune cells so that the immune system does not destroy them.

The goal of "immunotherapies" is to block immune escape mechanisms to help the immune system kill tumors. CD47 is a protein that lung tumors use to block the immune system from killing them. Research suggests that immunotherapies that block CD47, referred to as "CD47 blockade", could be effective in lung cancer. Yet, CD47 blockade has not worked well in patients in clinical trials. This difference in the anti-cancer effects of CD47 blockade in the laboratory and the clinic indicates more research is needed to understand how to use CD47 blockade effectively.

The goal of our project is to develop a new way to make CD47 blockade work better in lung cancer patients. We have devised a strategy that uses viruses to deliver CD47 blockade to lung tumor tissues so that it works better with fewer toxic side effects. We will test these viruses in different lung cancer models to determine whether they effectively kill lung tumors. We will also conduct studies to understand how cancer cells and the immune system respond to our virus therapy.

These studies will inform strategies to refine the virus to enhance their ability to kill lung tumors. Our research will establish a new way to unleash and maximize the efficacy of CD47 blockade in lung cancer. This will advance the development of CD47 blockade so that it can be used to treat lung cancer patients who cannot be treated with currently approved immunotherapies. As such, the results of our work could positively impact thousands of lung cancer patients in Canada and worldwide each year by providing a new and effective treatment option.

Hoon-Ki Sung, Hospital for Sick Children (SickKids)

Obesity is one of the most significant health challenges facing Canadians today. Treatments such as calorie-restricted diets and newer weight-loss medications can be highly effective, but most people regain weight after stopping treatment - and often end up metabolically worse than before they started.

We believe this happens because adipose tissue, commonly known as fat tissue, undergoes harmful changes during weight regain that prevent it from recovering normally. Under healthy conditions, fat tissue regains its mass by generating new fat cells - a process called hyperplasia. Our research shows that after rapid weight regain, this regenerative process fails. Instead, fat tissue develops fibrosis - a scarring-like condition associated with inflammation and impaired metabolic function. Importantly, our preliminary data show that simply slowing the rate of weight regain during the first week after treatment is stopped completely prevents this scarring, suggesting that the problem is not weight regain itself, but how fast it happens.

This project will investigate why rapid weight regain causes fat tissue to scar rather than regenerate, identify the critical early window during which this process can still be reversed, and test whether blocking a key metabolic signal called mTORC1 can prevent harmful remodeling.

We will also examine whether the same process occurs in people who stop taking GLP-1 receptor agonists, a class of weight-loss medications now widely prescribed across Canada, establishing whether our findings apply to the growing number of patients cycling on and off pharmacologic therapy. By reframing weight regain as a biological process that can be intercepted rather than an inevitable outcome, this research will open new directions for protecting long-term metabolic health in Canadians living with obesity.

Daniel Winer, Toronto General Hospital: University Health Network (UHN)

Aging is associated with an increase in most chronic diseases. With an increasingly elderly global population, aging is creating an enormous and growing health, social, and economic burden.

In recent years, research has identified several key molecular and cellular causes of aging, with one of these causes being a low-grade inflammation within the body. This persistent inflammation with age is also known as "inflammaging" and is associated with age related reduced immune cell robustness, called "immunosenescence".

T cells of the adaptive immune system are one key immune cell contributing to this weakened immune response with age. Specifically, T cells lose their diversity and function, hampering their response, though the reasons why are not understood. Moreover, T cells are pushed into a state of increased basal inflammation, also contributing to their dysfunction. These T cells can accumulate inside old tissues to cause disease and even the aging process itself, though the factors that drive them into dysfunctional aging states are still not entirely known.

In this study, we focus on understanding why immune cells, like T cells, lose their function with age. Interestingly, we found that T cells inside mice that lack B cells show almost no signs of aging, suggesting that B cells are required to induce aging in T cells.

We will:

1. map out how B cells communicate with T cells in immune organs like the spleen across age
2. use mouse models to better define mechanisms by which B cells can age T cells
3. utilize this knowledge to develop putative therapies aimed at improving old T cells.

This work will provide new insight into how the immune system ages with relevance to the numerous chronic diseases of aging.

Michelle Bendeck, University of Toronto, MaRS Centre

The diseases atherosclerosis, restenosis and bypass graft failure are the leading causes of morbidity and mortality and are responsible for >45,000 deaths in Canada each year. The current standard of treatment for atherosclerosis is to insert a drug eluting stent, to limit narrowing of the arteries that occurs in atherosclerosis and restenosis. However, the drugs currently used kill cells non-selectively and can therefore damage the protective endothelial cell layer that lines the artery. This can result in blood clots forming and occluding the artery, a process called restenosis. Moreover, stenting is not used for all conditions and is of limited use in occlusive peripheral artery disease, which is common in people with diabetes.

We have devised an approach to inhibit the migration of smooth muscle cells which move into the inner layer of the blood vessel after angioplasty or stenting, causing restenosis. We will use nanoparticles coated with a peptide which inhibits the growth of smooth muscle cells but spares the protective endothelial cell layer. These peptide-coated nanoparticles will be administered coated on balloon angioplasty catheters. The peptide and delivery system are novel and show great promise for use as therapies to treat atherosclerosis and other vascular diseases.

Jason Fish, Princess Margaret Hospital: University Health Network (UHN)

Brain arteriovenous malformations (bAVMs) are abnormal connections of blood vessels, where arteries directly connect to veins. Because the blood travelling through the arteries is moving at high speed and is under high pressure, this causes the veins to change their shape. Over time, this results in the formation of a tangle of blood vessels, which can balloon out and eventually rupture. This is the leading cause of blood vessel rupture (stroke) in young people.

Most bAVMs do not run in families but instead show up without warning. We recently discovered that most bAVMs are caused by a single mutation in a gene called 'KRAS' that occurs in endothelial cells - cells that line the blood vessel.

For many years we have been trying to understand how KRAS mutations affect the way that endothelial cells behave. Usually, endothelial cells form a tight barrier between the blood and the brain tissue. Once blood vessels have formed, they are very stable and do not usually remodel. We have found that KRAS mutations cause the endothelial cells to move around and to form new connections. The cells are also larger, which means that the abnormally connected vessels have a larger diameter. Because the cells move around a lot, the vessels are fragile and prone to rupture.

Our project will seek to understand why KRAS mutations result in these cell behaviours. Many of these behaviours depend on making more energy and raw materials for cell growth and migration. We have seen that the DNA is very active in these cells and turns more genes into proteins (a process called 'hypertranscription'). We will seek to understand what controls this process and whether this can be blocked as a way to treat these vascular malformations. Since 'hypertranscription' may result in damage to the DNA, we will test whether drugs that enhance DNA damage-induced cell death can prevent vessels from abnormally remodelling.

Rajiv Gandhi and Mohit Kapoor both Department of Surgery, Toronto Western Hospital: University Health Network (UHN), (with colleagues Divya Sharma, Anthony Perruccio, Raja Rampersaud and Sarah Rice)

Osteoarthritis (OA) is a leading cause of pain and disability, affecting over 500 million people worldwide, including millions in Canada. The knee is the most commonly affected joint, and for advanced disease, total knee replacement surgery (total knee arthroplasty, or TKA) is often the only option.

While many patients benefit, up to one-third experience little or no improvement, which shows that knee OA (KOA) is not the same in everyone. Biological differences between patients, called endotypes, and differences in treatment response, called theratypes, may explain these outcomes. Currently, doctors classify KOA mainly by symptoms or imaging, but these methods cannot fully capture the complexity of the disease.

Our project will use "multi-omics," which are advanced laboratory tests that measure thousands of molecules in blood, joint fluid and urine, including genes, proteins, metabolites and small RNAs, to create a detailed picture of each patient's biology. Because this produces enormous amounts of complex data, we will use artificial intelligence (AI) and deep learning to combine all the information and identify patient subgroups with distinct biological mechanisms.

In the first stage, we will expand molecular profiling of 414 KOA patients who have had TKA. In the second stage, we will use AI to refine biological subgroups (endotypes). In the third stage, we will apply machine learning to link these profiles to surgical outcomes, identifying theratypes that predict who will benefit most from surgery.

By uncovering these patterns, we aim to guide more personalized KOA care by matching patients to the right treatments, improving quality of life, avoiding unnecessary surgeries, and informing better clinical trials. This research brings together scientists, clinicians, and patient partners, ensuring that findings can be translated into real-world tools to support decision-making and reduce the burden of KOA on patients and the healthcare system.

Vinod Chandran (Department of Medicine), Toronto Western Hospital: University Health Network (UHN) (with colleague Igor Jurisica)

Psoriasis is a common chronic inflammatory skin disease that affects more than a million Canadians. Many patients with psoriasis also develop a specific form of arthritis called psoriatic arthritis (PsA). Patients with psoriasis and psoriatic arthritis have flaky, red, itchy skin, joint destruction, limitation of function and poor quality of life.

Psoriasis and PsA manifest uniquely in males and females. Our preliminary study found evidence of environmental factors being important in the development of PsA, affecting males and females differently. These environmental factors cause PsA and include small molecules produced by microbes in the gut. We propose to further evaluate these interesting findings by determining whether there are sex-specific small molecules including microbial metabolites associated with the transition from psoriasis to PsA, and in patients with PsA of recent onset.

These studies will be conducted using samples taken from patients who have been carefully evaluated at our centre. We will use mass-spectrometry-based methods to identify small molecules and analyze the data with advanced statistical and machine learning methods. Based on the results, we will design a larger study to identify small molecules and pathways associated with the development of PsA. This might lead to identifying novel pathways that lead to the development of PsA in patients with psoriasis, and potentially preventive therapy.

Robert Kozak, Sunnybrook Health Science Centre - Operating Grant: Leadership Award for Vaccine Research

Orthoparamyxoviruses are a subfamily of viruses that include multiple human pathogens. Within it there are several genera that are of concern due to their pandemic potential, these include:

• Respiroviruses (includes parainfluenza viruses 1 and 3 and human metapneumovirus which accounts for significant morbidity every year, as well as thousands of deaths, particularly amongst children, the elderly and the immunocompromised)
• Pneumoviruses
• Henipaviruses (includes Nipah virus (NiV) and Hendra virus, both zoonotic infections with case fatality rates ranging from 40-90%, and Langya virus, which has caused non-fatal infections in China, and the pandemic potential remains unknown)

We seek to develop mRNA vaccines that contain multiple antigens and will provide broad protection against these viruses. These vaccines will undergo safety, immunogenicity and challenge studies in multiple animal models to generate pre-clinical data.

Collectively, this has the potential to improve Canada's pandemic preparedness through vaccine development by building research capacity thereby making us more ready to respond to global infectious disease threats.

Slava Epelman (Department of Medicine), Toronto General Hospital: University Health Network (UHN)

Heart failure is a devastating disease that affects millions of Canadians. Many different risk factors contribute to its development; however, no single risk factor is predictive, suggesting a multi-factorial cause. High blood pressure (hypertension) and viral infection both strongly shape immune responses and are known risk factors, yet most individuals who have either one alone never develop heart failure.

In our research, we found that viral infection in mice with chronic hypertension triggered greater heart damage than non-hypertensive mice. This increased damage was severe enough to progress to heart failure, while the same infection in healthy mice led to minimal injury. Our findings show that high blood pressure makes the heart more vulnerable to immune-mediated injury during an otherwise mild viral infection.

This project will investigate how high blood pressure disrupts immune regulation within the heart and impairs host responses to viral infection. By researching the immune mechanisms of susceptibility, we aim to understand how two common conditions interact to drive pathological inflammation and heart damage, which may guide strategies to identify at-risk individuals.