Courtney Marshall
Christiane Whetstone
Vincent Dandenault
Tony Guo
Nadia Suray Tan
Early Career Researcher Award in Asthma
Dr. Cristina Longo
Treating Asthma by Integrating Learning Algorithms with Omics
Research: Moving toward Automated High-Dimensional
Endotyping in Children (TAILOR-MADE)
Asthma is a common lung disease in children, which can cause severe breathing problems and affect their quality of life. When asthma symptoms happen, many kids will visit their doctor for a diagnosis and treatment. Doctors often treat asthma symptoms with medicines that you inhale. A major problem is that these medicines do not always work. This is because asthma has many different disease processes that need targeted treatments. Although we do not know much about these disease processes, we can understand more by collecting biological samples, like blood, breath, or saliva, and analyzing them with new technologies. These samples contain millions of signals or ‘biomarkers’ that can help us discover new disease processes for childhood asthma. However, this large amount of data makes it challenging to find which biomarker might be important. We now have advanced computer tools, like machine learning, that can help us address this ‘big data’ problem. My research program uses machine learning to discover important biomarkers and different disease processes in children with asthma symptoms that can help doctors predict their response to treatment. This will help doctors identify which children will benefit from treatment or develop new medicines for those that will not benefit.
This award was jointly funded by Asthma Canada, AstraZeneca Canada, the Canadian Allergy, Asthma and Immunology Foundation (CAAIF), the Canadian Institutes of Health Research’s Institute of Circulatory and Respiratory Health (CIHR-ICRH) and the Canadian Lung Association.
Early Career Researcher Award in Asthma
Dr. Zihang Lu
Asthma phenotypes, risk factors and the implications for future
management in Canadian children
In preschool, defining asthma is challenging due to a lack of objective measures along with a heavy reliance on a non-specific symptom of wheeze and a diverse clinical course reflected by remission and relapse. Earlier research shows that asthma is likely caused by several different pathways that are influenced by genetic and environmental factors. We believe these disparate pathways reflect different types of asthma and we aim to identify these pathways in early life using objective methods. To do this, we will use two research data platforms, namely the CHILD Cohort Study and the Canadian Urban Environmental Health Research Consortium. The first aim is to define distinct asthma phenotypes by applying data-driven methods to asthma traits (e.g. wheeze, atopy, body mass index), and to determine whether these phenotypes are different in males and females. The second aim is to determine early-life risk genetic and environmental factors associated with these distinct phenotypes. This study will address several knowledge gaps in our understanding of early life asthma phenotypes and the influences of genetic and environmental exposures on these phenotypes. It will also promote future studies to understand the underlying disease mechanism and provide important evidence to develop disease prevention and management strategies.
This award was jointly funded by Asthma Canada, AstraZeneca Canada, the Canadian Allergy, Asthma and Immunology Foundation (CAAIF), the Canadian Institutes of Health Research’s Institute of Circulatory and Respiratory Health (CIHR-ICRH) and the Canadian Lung Association.
CAAIF Research Fellowship in Type 2 Inflammation
Supported by Sanofi Canada
Dr. Jasmine Barra
Elucidating the mechanism of action of IL-5 as a promoter of IFN
production and NK activation
Allergic asthma is a life-threatening disease. When asthmatic individuals get the flu, caused by viral infection, their airways become heavily inflamed and obstruct with mucus, potentially triggering an asthma attack. To find new treatments to help asthmatic patients deal with viral infections, we focus on one special cell type, the mast cell.
Mast cells are immune sentinel cells, critical for effective response to many pathogens, including viruses. Mast cells recruit immune cells, called natural killer (NK) cells, to the site of infection. NK cells are important because they kill the cells infected by the virus, reducing inflammation. Both recruitment and killing ability of NK cells are boosted by interferons, an important class of chemical messengers. A recent discovery from our Lab showed that, during viral infection, mast cells exposed to interleukin-5 produce greater amounts of interferons, suggesting they could improve antiviral response. Interleukin-5 is a type 2 cytokine, a molecule found elevated in allergic diseases and the target of most common therapies to control asthma.
We propose to investigate how interleukin-5 increases the production of interferons in mast cells. Results from our study will indicate how to promote interferon production during antiviral responses, with important benefits for patients with asthma.
CAAIF Research Fellowship in Type 2 Inflammation
Supported by Sanofi Canada
Dr. Kyle Burrows
Commensal protozoan driven remodeling of lung immunity
Asthma remains a major global health burden that can affect all social classes. The broad range in vulnerability and severity of asthma across populations suggests that there are still unknown risk factors associated with this disease. The gut microbiota, the collection of all microbes living within our intestines, plays an essential role in balancing immune responses and is known to regulate immune cells in the lung via host-microbiota interactions across the ‘gut–lung axis’. Our group has identified a new intestinal protozoan microbe, Tritrichomonas musculis (T.mu), that can shape the local gut immune system. Interestingly, T.mu can also alter immune cell function along the gut-lung axis and bias the lung toward an inflammatory state as well as exacerbate disease following induction of an experimental model of asthma. However, the interactions between the gut and lung immune cells that promote this inflammation are not known. My proposal aims to characterize the changes in immune cell organization within the lungs of mice carrying T.mu in order to uncover how T.mu driven signals across the gut-lung axis can promote lung inflammation. Overall, our results will reveal how T.mu, as an environmental risk factor, can influence the development of asthma.
CAAIF Research Fellowship in Immunology
Supported by Takeda Canda
Dr. Anikó Malik
Investigations of B cells in common variable immune deficiency and autoimmunity
The immune system is a complex network of white blood cells and proteins known as cytokines. Specific antibodies produced by the immune cells defend the body against infection. Immune system dysfunction can lead to repeated, potentially fatal infections (immunodeficiency) and chronic inflammation when the immune system attacks the body’s own tissues (autoimmunity). Common Variable Immune Deficiency (CVID), the most common type, causes a halt in the development of specific blood cells (B-cells), which normally produce protective antibodies. In some patients, it is caused by a genetic mutation; however, in the majority of patients, the cause of poor antibody production is unknown, and the disorder can manifest at any age, including in older adults. Even with the best care, these patients are vulnerable to autoimmunity, which shortens their lives and lower their quality of life. We are investigating the cause of decreased antibody production and how impaired B-cell function leads to autoimmunity. Understanding the basis of dysregulated antibody synthesis should help not only with CVID treatment, but also with the treatment of many chronic inflammatory disorders caused by autoantibodies, such as lupus, arthritis, multiple sclerosis, and others. Mechanism-based therapies should improve patients’ quality of life while reducing the healthcare system’s burden.
CAAIF-Miravo Healthcare Research Grant in Allergic Rhnitis or Urticaria
Dr. Jörg Fritz
Treating allergic rhinitis by blockade of triacylglyceride synthesis
The type 2 immune response is critical for host defense against parasites, wound healing and body metabolism. However, dysregulation of type 2 immunity causes immunopathological conditions, including allergic rhinitis, asthma, atopic dermatitis and anaphylaxis, atopic diseases that also have been referred to as type 2 immunopathologies. Thus, a balanced type 2 immune response must be achieved to mount effective protection against pathogens while avoiding detrimental diseases.
Recent clinical evidence demonstrates that elevated levels of the alarmin interleukin (IL)-33 and group 2 innate lymphoid cells (ILC2) have been found in patients with allergic rhinitis and have been suggested to be key in driving disease. To define novel drug targets for treatment we analyzed molecular signatures leading to dysregulated type 2 immune responses and identified an enzyme involved in triacylglyceride (TAG) lipid metabolism, diacylglycerol acyltransferase 2 (DGAT2), to be central to drive disease. In this study we will test of whether pharmacological inhibitors of DGAT2 (currently used in clinical trials for the treatment of steatosis) and dampen pulmonary allergic immunity and rhinitis. These experiments will allow us to judge of whether repurposing DGAT2 inhibitors should be considered as a promising potential novel therapeutic approach for the treatment of allergic rhinitis.
CAAIF Top 10 Challenge Food Allergy Research Grant
Dr. Bruce Mazer
Processing and characterizing peanuts for a safer and more efficacious substrate for desensitization of peanut allergy
Peanut allergy is extremely common, affecting nearly 1 in every 100 children in Canada and the USA. Recent advances in treatment have emerged in the form of oral immunotherapy (OIT), a controlled process whereby patients are fed progressively larger quantities of peanuts with the goal of building tolerance. However, current OIT protocols do not lead to complete tolerance, and patients still have a significant risk of allergic reactions throughout treatment. Thus, there exists a critical need for a safer and more effective way to treat peanut-allergic patients.
We hypothesize that high-pressure and temperature autoclaving can reduce peanut allergenicity by decreasing the quantity of intact allergenic proteins relative to roasted peanuts. We will determine the optimal autoclaving conditions needed to strike a critical balance between breaking down the peanut enough so that it is safer to consume than roasted peanuts, while simultaneously leaving enough allergen intact so it can effectively build up a tolerance.
For the thousands of individuals and their families suffering from peanut allergy across the globe currently forced to abide by strict avoidance diets, this transformative work could lead to a novel OIT treatment that enables improved or complete tolerance to peanuts, significantly improving their quality of life.
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Graduate Student Award in Asthma
Living (Darlene) Dai
Mining the infant gut microbiota to predict and prevent asthma: data from the CHILD Cohort Study
Asthma is a potentially life-threatening condition that is, unfortunately, the most common chronic disease of childhood, affecting 1 in 7 Canadian children. While treatments can help manage symptoms, there are no curative therapies, which often leads to life-long burdens for diagnosed children. Predicting which children are at-risk of developing asthma and preventing the onset of this disease are therefore key to reducing its burden.
Our research group, and others around the world, have linked the development of asthma to an imbalance in the beneficial community of resident bacteria, called the microbiota, that colonize the guts of infants. This discovery presents a unique opportunity to: (i) identify populations of bacteria that when present in early life in the gut can predict risk of future disease; and (ii) understand these bacteria and use this knowledge to develop preventative strategies based on modifying the composition of the community of bacteria living in the infant gut.
In this research program we will use powerful new genetic sequencing technologies that can profile an infant’s entire microbiome from stool samples to identify functional microorganisms and predict which children will go on to develop asthma. More broadly, our research will guide the development of safe ways to replace missing healthy microbes to prevent asthma from developing in the first place.
This award was jointly funded by Asthma Canada, the Canadian Allergy, Asthma and Immunology Foundation (CAAIF) and the Canadian Institutes of Health Research’s Institute of Circulatory and Respiratory Health (CIHR-ICRH).
Graduate Student Awards in Asthma
Harkiran Kooner
Are CT Mucus Plugs disrupted following two years of Benralizumab treatment in severe, eosinophilic asthma?
Severe, eosinophilic asthma is characterized by airway inflammation and luminal obstruction that occurs as a result of eosinophils in the airways. These patients often report frequent exacerbations and reduced quality-of-life, despite treatment with high-dose medication. Airway mucus plug formation can be encouraged by mucin-eosinophil interactions in the airways and the associated symptoms and airway obstruction are not easily reversed using commonly prescribed asthma therapies. Benralizumab, an interleukin-5 biologic therapy, reduces airway eosinophilia. Thus, this research will investigate whether the elimination of airway eosinophils by benralizumab will alter the presence of mucus plugs, quantified via CT imaging, in the airways of asthma patients after two years of treatment. Based on previously published work, we hypothesize that severe asthma patients with a greater number of mucus plugs prior to treatment will have a greater improvement in quality-of-life and asthma control following benralizumab as a result of the disruption of mucus plugs in their airways. Confirmation of this concept using CT imaging immediately prior to and following two years of therapy will provide the foundation necessary for precision-medicine to target mucus occlusions in patients with poorly-controlled, eosinophilic asthma who do not find relief with traditional asthma therapies. Therefore, this project can identify patients with asthma whom would benefit most from biologic treatment, leading to significantly improved quality-of-life and asthma control in this subset of severe asthma patients.
This award was jointly funded by Asthma Canada, the Canadian Allergy, Asthma and Immunology Foundation (CAAIF) and the Canadian Institutes of Health Research’s Institute of Circulatory and Respiratory Health (CIHR-ICRH).
Graduate Student Award in Asthma
Fang Fang Li
Uncovering viral determinants of asthma development by serological profiling
Worldwide prevalence of asthma has been increasing over the last decade, with higher rates recently observed in industrialized countries. The current leading theory best explaining the worldwide disparity is the hygiene hypothesis, which suggests that exposures to microorganisms during early childhood are essential to preventing immune-related conditions such as asthma by school-age. Supporting the hygiene hypothesis, several studies have demonstrated a protective effect against allergies and asthma in those exposed to Epstein-Barr virus, a common respiratory virus, in their childhood. However, recent research has also demonstrated that other common respiratory viruses, such as human rhinovirus and respiratory syncytial virus, can instead increase the risk of asthma development, thus challenging the hygiene hypothesis. Alongside recent work implicating viral gastroenteritis as another potential risk factor for asthma, we believe that all viral infections could potentially influence the risk of asthma development by school-age, though the direction is virus-dependent. This project aims to link together the complex relationships between asthma and viral infections in young Canadians using Canada’s largest birth cohort, the Canadian Healthy Infant Longitudinal Development (CHILD) study. By uncovering the combinations of viral infections influencing asthma outcome, we can direct new avenues of asthma research and ultimately design better strategies for the prevention and treatment of asthma.
This award was jointly funded by Asthma Canada, the Canadian Allergy, Asthma and Immunology Foundation (CAAIF) and the Canadian Institutes of Health Research’s Institute of Circulatory and Respiratory Health (CIHR-ICRH).