Research Project: Development of 3D in vitro lung airway models to investigate the role of hypoxia in airway remodeling in asthma 

Asthma is a chronic inflammatory lung disease, and subepithelial fibrosis (SF) is one of its hallmarks. This fibrosis is caused by excessive accumulation of extracellular matrix (ECM) proteins – especially collagen type I. This makes the airways become thickened and obstructed, leading to tissue stiffening and a reduction in lung function. Obstructed airway reduces oxygen supply to the tissues. Evidence shows that low oxygen concentration in the lungs (known as “hypoxia”) regulates the production of ECM proteins (such as collagen type I), enzymes, etc. 

The interactions between the ECM and tissue-resident cells, the mechanisms driving ECM alternations in asthma, and the role of oxygen in this process are poorly understood. This research will be the first to integrate two novel technologies, multimodal Raman microspectroscopy and Second Harmonic Generation (RM-SHG), and high-resolution Nonlinear Optical Microscopy (NLOM) to understand fundamental mechanisms associated with low oxygen levels (hypoxia) and ECM alternation in asthma. 

Research Project: Sex as a biological variable in immunomodulation of airway inflammation by Innate Defence Regulator (IDR) peptides

Asthma is the most common chronic respiratory disease affecting nearly 3 million Canadians including children. Around 15% patients do not respond to available steroid therapies and represent the major burden of asthma accounting for annual healthcare costs of $2B. Also, common steroid therapies can increase the risk of lung infections, which can make asthma worse. New therapies are urgently needed that can alleviate steroid-unresponsive disease without compromising the ability to resolve infections.

There is a clear sex bias in asthma, for example adult females experience greater disease severity and are more likely to develop steroid-resistance, compared to males. These sex-related differences are largely ignored during drug development. Effective development of new treatments must consider the differences in disease and response to therapy between females and males.

This study focuses on new molecules known as innate defence regulator (IDR) peptides, which can control both inflammation and infection. We have shown that IDR peptides improve breathing capacity in an animal model of asthma, and control cellular processes linked to steroid unresponsiveness. This project aims to develop IDR peptides as a new therapy for asthma, by examining the effects in both females and males concurrently. This research will directly support the development of a new IDR peptide-based therapy for asthma, by taking into consideration how the treatment affects females compared to males. It is entirely possible that we will need to develop sex-specific treatment protocols to provide the most efficient care for asthma sufferers.

Insight into the fibrotic responses in asthma with an unprecedented level of spatial and biochemical specificity will drive the identification of biomarkers active in disruptive airway remodelling and support therapeutic development minimizing the formation of scar tissue observed through the excessive burden of SF.

Research Project: Investigating the role of airway epithelial cell (AEC)-derived semaphorin3E in chronic type-2 high and steroid-resistant type-2 low models of asthma

Asthma is a major health concern in Canada, while inhaled corticosteroids (ICS) are the first-line treatment for persistent asthma, some patients have a poor response to these drugs. This condition is known as steroid-resistant asthma (SRA), with type 2-low (neutrophilic) asthma being a major phenotype of SRA. Understanding the mechanisms behind this resistance is crucial for developing better treatments.

Our research focuses on Semaphorin3E, a protein that our lab has found to reduce asthma severity in preclinical models. Sema3E decreases airway sensitivity, inflammation, and lung tissue scarring. Healthy human lungs naturally produce Sema3E, primarily from airway epithelial cells (AECs). However, in severe asthma cases, Sema3E levels are lower, correlating with decreased lung function, indicating its role in maintaining lung health.

Using two chronic (type-2 high) eosinophilic and (type-2 low) neutrophilic asthma models, we aim to study the effects of AEC-derived Sema3E on asthma. We will also compare the impact of Sema3E with dexamethasone, and explore the combination of both treatments.

Research Project: Evaluating small-airways remodeling and response to therapy in patients with severe asthma using 129Xe MRI ventilation texture features.

Asthma is a chronic lung disease characterized by airway remodelling, chronic inflammation, airway wall thickening, and lumen narrowing. Several clinical tools exist to help diagnose and monitor airway dysfunction. However, these approaches provide measurements that are relatively insensitive to small-airways dysfunction and its associated patchy ventilation which is believed to drive asthma symptoms and worsening.

To address this gap, our project proposes the use of pulmonary functional MRI with inhaled hyperpolarized 129Xe gas. This method has shown promise in previous studies for detecting airway dysfunction with high sensitivity. By tracking small-airways abnormalities, we have an opportunity to enhance our understanding of how the airways respond to asthma therapy. This information will help focus new treatments targeting small-airway abnormalities which we think will lead to better asthma patient outcomes overall. 129Xe MR images will be analyzed using texture analysis—an image analysis technique to determine if the patterns in the MRI reveal abnormalities in lung ventilation due to asthma. By employing machine learning models to these texture features, we aim to identify which are most indicative of changes in the airways, potentially outperforming traditional clinical measurements. This information will be vital in guiding improved treatments for asthma, leading to better patient outcomes.

Research Project: Exploring the molecular interactions between early-onset asthma and cow’s milk allergy

Childhood asthma and food allergies frequently occur together, affecting millions of children globally. Studies show that 4-8% of asthmatic children also have food allergies, and about 50% of children experiencing allergic reactions with respiratory symptoms have food allergies. Despite this common overlap, the reasons behind this connection or how these conditions influence each other at a molecular level remain poorly understood. This study aims to uncover the molecular link between cow’s milk allergy (CMA) and worsening asthma symptoms.

We hypothesize that specific components of cow’s milk proteins, when broken down during digestion, release fragments that trigger allergic pathways, potentially exacerbating asthma. By focusing on cow’s milk as a model system, the aim is to gain insights that can be applied to other food allergies as well. Utilizing advanced computational tools and bioinformatics techniques, this research seeks to identify and analyze these specific protein fragments, simulate digestion processes, and examine how they interact with the immune system. Additionally, a machine learning model will be developed based on data from children with CMA. This model will then be used to help us predict if other milk alternatives or food proteins might also worsen asthma symptoms.

The goal is to improve quality of life for affected children by better understanding how CMA may worsen asthma. Our findings could lead to improved risk prediction, more targeted treatments, and personalized dietary advice for children with both conditions.

Research Project: An evaluation of gas-exchange abnormalities in moderate-severe asthma over time.

Asthma is a disease that inflames and narrows the airways, so treatments usually focus on relieving airway symptoms. However, new research suggests that other parts of the lungs, like blood vessels and the alveoli where gas exchange takes place, might also be involved in asthma. Studies indicate that lung blood vessels may change in severe asthma, similar to serious heart disease. We aim to understand the role of these pulmonary blood vessels and areas of gas exchange in asthma patients.

Using hyperpolarized 129Xe magnetic resonance imaging (MRI) and spectroscopy, we can visualize and measure gas exchange and ventilation in the lungs. We plan to evaluate 129Xe MR gas-exchange measurements in a large group of asthma patients with varying severity and age-matched healthy individuals. We will also follow a subset of moderate-to-severe asthma patients over time to see how their gas-exchange measurements change with treatment.

While gas-exchange abnormalities and blood flow changes are known in many diseases including COVID-19, few studies have examined gas-exchange in asthma with large participant groups. This project will be the first large-scale investigation to explore whether gas-exchange and blood vessel abnormalities are linked in asthma. By comparing healthy individuals with asthma patients and observing changes over time with treatment, we aim to confirm these gas-exchange abnormalities, potentially establishing them as a new treatable trait in asthma beyond the airways.

Research Project:  Data from the CHILD cohort study: functionally linking the early-life gut microbiome to health and disease

Allergic diseases affect hundreds of millions of children worldwide and continue to increase in prevalence. Many risk factors for allergic diseases, such as antibiotic usage, also influence microbes and their genes within the gut, which, together, are commonly known as the gut microbiome. Maturation of the gut microbiome usually occurs at the same time as the development of healthy immune tolerance. However, if microbiome maturation is abnormal, allergic sensitization can emerge in some children as a result.

My research combines school-age allergic diagnoses with early-life gut microbiome composition, functional capability, and metabolite concentrations for the quantification of a ‘normally’ maturing gut microbiome. This data primarily stems from CHILD (n=3,455), a large Canadian longitudinal study with robust information on participant environment and microbiome. To increase the strength and relevance of my findings, I will not only identify associations in CHILD, but I am also working with my colleagues and collaborators to validate our findings in other populations with clinical and microbiome data, such as the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). 

The aims of my research are to (1) identify unifying gut microbiome maturation signatures in asthma, allergic rhinitis, food allergy, and atopic dermatitis, collectively called the ‘Allergic March’, (2) functionally link antibiotic usage to the onset of specific allergic diseases using microbiome data, and (3) connect microbial-dependent influences on participant immune cell profiles to allergy. My investigation of the early-life gut microbiome will thus empower new predictive and preventive strategies to avoid allergic diseases.

Research Project: Mapping airway remodelling in asthma using multimodal Raman-Second Harmonic Generation imaging and machine learning

Asthma is a chronic inflammatory disease, impacting approximately 11% of the Canadian population. Inhaled allergens damage the tissue barrier lining the lungs, leading to the inflammation of airways and difficulties in breathing. To remodel impaired tissue, damaged airways trigger a complex cellular response, denoted by the excessive accumulation of extracellular matrix (ECM) proteins; particularly collagen I. Evidence suggests that this fibrotic response, known as subepithelial fibrosis (SF), contributes to tissue stiffening, airway blockage and an overall reduction in lung function.

With the goal of setting a new precedence for imaging and to better visualize ECM protein deposition at high resolution, our research applies a label-free multimodal imaging system embedded with the technologies of both Raman microspectroscopy and Second Harmonic Generation. This imaging system is the only of its kind in Canada, and is used to develop biochemical maps of tissues and cells while simultaneously detecting signals related to fibrillar collagen. Due to the complex nature of the data obtained, the development of novel approaches based on machine learning (ML) strategies to identify biomarkers associated with asthmatic airway remodelling is necessitated. Using ML, an automated classification pipeline will be developed to characterize spectral signatures unique to the basement membrane, epithelium and lamina propria of airways.

Insight into the fibrotic responses in asthma with an unprecedented level of spatial and biochemical specificity will drive the identification of biomarkers active in disruptive airway remodelling and support therapeutic development minimizing the formation of scar tissue observed through the excessive burden of SF.

Research Project: Sex as a biological variable in immunomodulation of airway inflammation by Innate Defence Regulator (IDR) peptides

Asthma is the most common chronic respiratory disease affecting nearly 3 million Canadians including children. Around 15% patients do not respond to available steroid therapies and represent the major burden of asthma accounting for annual healthcare costs of $2B. Also, common steroid therapies can increase the risk of lung infections, which can make asthma worse. New therapies are urgently needed that can alleviate steroid-unresponsive disease without compromising the ability to resolve infections.

There is a clear sex bias in asthma, for example adult females experience greater disease severity and are more likely to develop steroid-resistance, compared to males. These sex-related differences are largely ignored during drug development. Effective development of new treatments must consider the differences in disease and response to therapy between females and males.

This study focuses on new molecules known as innate defence regulator (IDR) peptides, which can control both inflammation and infection. We have shown that IDR peptides improve breathing capacity in an animal model of asthma, and control cellular processes linked to steroid unresponsiveness. This project aims to develop IDR peptides as a new therapy for asthma, by examining the effects in both females and males concurrently. This research will directly support the development of a new IDR peptide-based therapy for asthma, by taking into consideration how the treatment affects females compared to males. It is entirely possible that we will need to develop sex-specific treatment protocols to provide the most efficient care for asthma sufferers.

Research Project:  Basophilic oncostatin M fuels nociceptor neuron-induced asthma

Despite affecting less than 10% of asthmatic patients, severe asthma accounts for 60% of the asthma healthcare cost due to the lack response to corticosteroid treatments. Recent advance of single-cell gene profiling reveals a population of airway sensory neurons expressing similar genes as neurons sensing skin itch. However, molecular and pharmacological characterizations of this population are insufficient. With real-time calcium imaging, we can visualize the calcium influx, a neuronal activation event, in response to different stimulants. We can thus cluster the neurons based on their reactivity to different drugs as well as evaluate neuron’s sensitivity under normal and asthmatic condition.

We have thus far demonstrated that lysophosphatidic acid-responding neurons and serotonin-responding neurons are two distinct populations, which respectively represent jugular and nodose nociceptors in vagal sensory ganglia, from where the airway sensory neurons arise.

We also noticed that some jugular neurons express the receptor of oncostatin M (OSM), a cytokine associated with exaggerated itch sensation in atopic diseases. We then ask if OSM is expressed in asthmatic context and by which cells. With cell sorting and RT-qPCR techniques, we identified lung basophils as the main cellular source of OSM under normal and asthmatic conditions. As it sensitizes itch neurons, OSM can also sensitize vagal sensory neurons, shown by our calcium imaging data.

Whether OSM affects asthmatic pathophysiology through sensitizing airway sensory neurons is yet to be determined. We hope this novel neuroimmunology pathway provides a new possibility in seeking alternatives to glucocorticoid treatment.

Research Project:  DNA methylation changes induced by prenatal cannabis exposure associated with asthma in mice

Since legalization, there has been an increase in the use of cannabis in Canada, but worryingly there are few clear rules for its use and safety during pregnancy. Exposure to inhaled particulates in early life from other sources, including wildfires, tobacco smoke, or pollution, have known health outcomes leading to risk of asthma. Early life cannabis exposure has been studied extensively in the brain, but no clear evidence is available for respiratory conditions like asthma. We plan to examine the molecular effects of prenatal and early life cannabis smoke on asthma development by examining epigenetics, or change in DNA function without change in DNA sequence. Specifically, this project will use DNA methylation (DNAm) as it is the best characterized.

We know prenatal exposure to some environmental pollutants including tobacco smoke
causes changes in DNAm, but we do not yet know exactly how these changes cause lung problems like asthma. We will use a mouse model which will mimic our established tobacco exposure paradigm and expose pregnant mice to cannabis smoke. We will then examine their offspring’s lung tissue to find DNAm changes at specific genes. By comparing these changes with to our recent findings on DNAm changes due to tobacco exposure, we can identify common patterns that could indicate potential novel genes and their mechanisms in causing asthma.

We hope that by identifying the particular mechanisms involved, in the future we can prevent or reverse the negative impacts of cannabis and tobacco smoke on the lungs that increase the risk of asthma.

Research Project:  Quantitative Imaging to Understand the Early Manifestation and Therapeutic Relevance of Abnormal Airway Morphology and Function in Asthma

Approximately 3.8 million Canadians are living with asthma, a chronic disease that impacts the airways and makes breathing difficult. For most people with asthma, symptoms can be adequately controlled, and normal lung function can be maintained with medications that are delivered by inhalation. Unfortunately, however, some people with asthma are considered to have uncontrolled or more severe disease as commonly prescribed inhaled medications do not improve their symptoms, lung function, or risk of an asthma attack. There might be several reasons for this. One might be that anatomical abnormalities in the structure of the airways originate early in life, which are not hallmark and treatable components of asthma. Alternatively, inhaled medicines may not be reaching the right areas in the lungs due to abnormalities in the structure of the airways. Scientists have started to apply high-resolution medical imaging methods to study this. Using advanced magnetic resonance imaging and computed tomography techniques, we will investigate if abnormal features of airway structure: (1) are present, and explain reduced lung function, in early adulthood, (2) have unique temporal trajectories indicative of progressive or non-progressive disease in early adulthood, and (3) influence the effectiveness of first-line inhaled medications. Knowledge gained from this research will improve our understanding of airway disease in asthma and will be applied to improve how asthma is managed and how asthma medications are developed and delivered.

Research Project:  Investigating the interactions of air pollution and an anti-inflammatory asthma medication using scRNA sequencing

With the high prevalence of global air pollution, asthmatic individuals are at increased risk of developing respiratory complications. Asthma exacerbations can cause inflammation of the airways leading to breathing difficulties, necessitating the need for prescription medications. Inhaled corticosteroids (ICS) are a common asthma medication that reduces inflammation, but previous studies show that these medications are less effective following exposure to air pollutants. Despite prior research, the exact mechanisms of how ICS treatment is disrupted remain elusive. A lack of understanding between ICS and air pollution can cause medical practitioners to incorrectly access their patient’s condition, leading to under or overprescription of ICS and resultant adverse effects. Regardless of dosage, greater knowledge of ICS administration can aid in reducing treatment expenses by optimizing quality of care. For these reasons, the aim of this project is to understand how air pollution affects responses to ICS under well controlled conditions in human participants. More specifically, we can discern which cell-types and genes are directly involved in this process, with the hopes of identifying targets that may explain any decreased efficacy of ICS treatment following air pollution exposure.

Identification of gene targets can be determined using single-cell RNA sequencing technology, where we can find unique responses in individual cell-types and genes in ICS-treated participants exposed to air pollution or filtered air. Our research aims to guide improvements in ICS administration policies, ICS development or add-on medications to reduce the burden on healthcare services caused by air pollution.

2022 Recipient, Graduate Student Research Award

Christiane Whetstone

McMaster University

Research Project: 

“Effects of inhaled allergen on eosinophil phenotypes in blood and airways of patients with allergic asthma”

Christiane is a PhD candidate at the McMaster University. She completed her undergraduate degree at Queen’s University before joining the Medical Sciences Program (Physiology and Pharmacology) at McMaster and transferred from MSc to PhD program in 2020. Christiane’s research examines mechanisms of allergic disease with a specific focus on the role of eosinophil, basophils and their progenitor cells in airways and skin of allergic patients, using methodologies including immunofluorescence microscopy and flow cytometry. Her data is generated from clinical trials with interventions to deplete (benralizumab) or to induce (allergen challenge) eosinophilia. Her academic goal is to become a translation scientist continuing to develop targeting medicine. Outside of research, Christiane enjoys playing tennis and horseback riding.

2022 Recipient, Graduate Student Research Award

Courtney Marshall

University of Manitoba

Research Project: 

“Sex-related differences in immunomodulation of airway inflammation by Innate Defence Regulator (IDR) peptides”

Courtney Marshall is a PhD student in the Department of Immunology, University of Manitoba, in Dr. Neeloffer Mookherjee’s laboratory. Prior to this, she completed her undergraduate degree in Biology at the University of Manitoba with two Co-Op positions, the first at AdMare Bio-innovations in Vancouver, BC, followed by a position in the Mookherjee lab. This experience led to her pursuing graduate studies as a master’s student where she then successfully transferred into the PhD program to continue her research on defining the sex-related differences in the immunomodulation of airway inflammation by Innate defence regulator peptides. Ms. Marshall’s academic and research success has resulted in awards such as the CIHR-CGS (M) scholarship, the Mindel and Tom Olenik Entrance Scholarship, and the Research Award in Immunology. Following her PhD, Courtney hopes to obtain a post-doctoral position fellowship that allows her to transition into a leading independent Principal Investigator at a Canadian University.

2022 Recipient, Graduate Student Research Award

Darlene Dai

University of British Columbia

Research Project: 

“Mining the infant gut microbiota to predict and prevent asthma: data from the CHILD Cohort Study”

I have an MSc in Statistics from UBC and 7-year work experience as a biostatistician in discovering genomic biomarkers of cancer, heart and lung disease in academic and industry field. I am currently pursuing my PhD degree in Experimental Medicine at UBC under the co-supervision of Drs. Stuart Turvey (clinician-scientist) and Raymond Ng (data scientist). My research focuses on discovering and understanding the infant gut microbiome, metabolome, and epigenome compositions that in combination with host and environmental factors, can predict risk of early-onset asthma. By using CHILD Cohort Study, my PhD project aims to develop a precision health approach empowered by “omics” to predict, and ultimately to prevent early-onset asthma. Come meet me if you would like to learn more about me and my research!

In my free time, I enjoy spending time with my family, gardening and trying new restaurants.

2022 Recipient, Graduate Student Research Award

Fang Fang Li

University of British Columbia

Research Project: 

“Uncovering viral determinants of asthma development by serological profiling”

Fang Fang is a PhD student at the University of British Columbia in the Department of Pathology and Laboratory Medicine. Her research focuses on identifying and understanding the contributions of viruses in pediatric disease pathogenesis through the usage of adapted sequencing methodologies. She has previously been supported by an Undergraduate Summer Research Award from the Natural Sciences and Engineering Research Council of Canada as well as a Canada Graduate Scholarship – Master’s from the Canadian Institutes of Health Research for her work in linking immune responses to disease. In the future, Fang Fang hopes to discover and utilize new markers of pathogenesis to develop novel and minimally invasive prognostic and diagnostic tests for chronic diseases. When she’s not in the lab, Fang Fang enjoys teaching her dogs new tricks and curling up by the window with a good detective novel in hand.

2022 Recipient, Graduate Student Research Award

Harkiran Kooner

Western University

Research Project: 

“Are CT Mucus Plugs disrupted following two years of Benralizumab treatment in severe, eosinophilic asthma?”

Harkiran is a third-year PhD student in the Department of Medical Biophysics at Western University. Her research focuses on the use of hyperpolarized

¹²⁹Xe MRI and CT to evaluate structure-function relationships in asthma and post-acute COVID-19 syndrome. Harkiran’s research contributes to the growing body of evidence suggesting that the integration of imaging in clinical settings can help achieve the overarching goal in asthma of delivering the right intervention, to the right patient, at the right time. In the future, Harkiran aims to secure a research position with a clinical focus to continue her PhD work in pulmonary imaging and its use to improve patient outcomes.

2022 Recipient, Graduate Student Research Award

Nadia Suray Tan

McMaster University

Research Project: 

“Aberrant lymphocytes and airway autoimmunity: Connecting severe asthma and EGPA pathology.”

Nadia Suray Tan is currently pursuing her Master’s degree under the supervision of Dr Manali Mukherjee in Medical Science at McMaster University. She completed her Bachelor of Science with Honours (Distinction) in Life Sciences, specializing in Biomedical Science from National University of Singapore (NUS) and have been involved in translational research ever since. She joined NUS Immunology Programme (under the supervision of Dr Lim Hui Fang and Dr Veronique Angeli) and was involved in research on the immunopathology of severe asthma and other chronic lung diseases that were presented in various international conferences. Her previous work in NUS that focuses on the involvement of B cells in severe eosinophilic asthma was recently published in American Journal of Respiratory Cell and Molecular Biology. Nadia is a motivated and independent researcher with experience in areas of immunology, biochemistry, histology and translational research. Her current thesis work focuses on studying the lymphocyte mediated pathology that connects severe asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA), a rare, life-threatening autoimmune disorder. She hopes that her research will leverage her research experience and increase my depth of knowledge in asthma and airway research.

2022 Recipient, Graduate Student Research Award

Tony Guo

University of British Columbia

Research Project: 

“Characterization of the airway epithelial repair process in late-onset asthma following mechanical, viral, and particulate matter injury of the epithelium.”

Tony Guo is in his first year of his Master of Science program in Experimental Medicine at the University of British Columbia. His project will investigate how the repair mechanisms of the airway epithelium may be different in adult-onset asthma under the supervision of Dr. Delbert Dorscheid. He completed his Bachelor of Science program specializing in Physiology at UBC and his thesis project explored the airway epithelium’s responses to models of SARS-CoV-2 infection. With the support of Asthma Canada, CAAIF, and CIHR-ICRH, he aspires to contribute to the understanding of adult-onset asthma, whose underlying causes are currently not well defined, in an effort to improve the health and well-being of people living with asthma. During his program, he aims to mentor students interested in airway epithelial biology and asthma to support and guide them in their pursuit of research in the field.

2022 Recipient, Graduate Student Research Award

Vincent Dandenault

Univerity of Montreal

Research Project:

“Application of Bayesian networks to multi-omics data to improve the diagnosis of asthma in preschoolers.”

Vincent Dandenault is a graduate student doing research in the field of computational medicine at CHU Sainte-Justine Hospital in Montreal, Quebec. Coming from a background in software engineering, he is specialized in machine learning and looking to apply his set of skills, knowledge and experience in these complexe and powerful algorithms to the world of respiratory health, more specifically to the research and understanding of preschool asthma.

Currently, doctors do not fully understand the underlying mechanisms of asthma, and they can’t reliably test preschool aged children for asthma. Thus, they do not know which preschoolers with breathing difficulty actually have asthma or not, and who can benefit from available medication and treatments. Accordingly, Vincent’s primary goal as a researcher is to better understand the underlying mechanisms of asthma, and to ultimately link the current different observed phenotypes to different underlying pathways, leading to better diagnosis of preschool asthma, and consequently better patient care. Suffering from respiratory problems himself as a child, he can understand how scary and worrying asthma can be, notably asthma attacks and exacerbation, for patients and their loved ones. Ultimately, Vincent’s goal is to use machine learning to shed light on these problems.

2022 Recipient, Early Career Researcher Award in Asthma

Dr. Cristina Longo

Université de Montréal

Research Project: 

Treating Asthma by Integrating Learning Algorithms with Omics Research: Moving toward Automated High-Dimensional Endotyping in Children (TAILOR-MADE)

Asthma is a disease of the lung and is common in kids. Asthma symptoms happen when your airways tighten and swell, causing breathing problems like wheezing.  Another word for swelling is inflammation. Sometimes the inflammation could make it very hard to breathe. This is an asthma ‘attack.’ Asthma attacks are more common in preschoolers than other age groups. When asthma symptoms happen, kids need to visit their doctor for a diagnosis and treatment. Sometimes, doctors cannot confirm asthma in young children because they are unable to perform the test needed for a diagnosis. On the other hand, they can try to treat the inflammation that happens with asthma symptoms by prescribing medicines that you inhale. A major problem is that these medicines do not always work. This led scientists to try to understand why that is.

Scientists now think that asthma is not just one disease, but many different diseases that need different medicines. We still do not know much about these different diseases in children who have asthma symptoms. But we think that we can understand a lot more about the disease processes by collecting different biological samples, like blood, breath, or saliva, from children and then analyzing them with new technologies. The samples contain signals that can help us identify the different disease processes. These signals are also called biomarkers. There are millions of biomarkers in the body and this large amount of data makes it challenging to find which biomarker might be important for the disease process. We now have advanced computer tools, called machine learning, that can help us with this ‘big data’ problem.

The goal of my research is to use machine learning to discover important biomarkers of different disease processes in children with asthma symptoms that can help doctors predict whether asthma medicines will work well in them. To do this, my research team will analyze clinical and biological biomarker data from 282 preschoolers and children with asthma symptoms. We expect the results to help doctors identify which children will benefit from treatment or help develop new medicines for those that will not benefit. 

2022 Recipient, Early Career Researcher Award in Asthma

Dr. Zihang Lu

Queen’s University 

Research Project:

Asthma phenotypes, risk factors and the implications for future management in Canadian children

Asthma is the most common chronic disease of childhood, usually beginning in preschool and lasting through adulthood. In preschool, defining asthma is challenging for two reasons – 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 tells us that asthma is likely caused by several different pathways that are influenced by genetic and environmental risk factors. These pathways are defined by their clinical traits during their later life, e.g. persistent wheeze, transient wheeze. We believe these disparate pathways reflect different types of asthma (asthma phenotypes)  and we will try to move towards a more objective method to identify these pathways in early life. To do this, we will use two research data platforms, namely the CHILD Cohort Study and the Canadian Urban Environmental Health Research Consortium (CANUE). 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 key 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 as well as the influences of genetic and environmental exposures on these patient phenotypes. It will also promote future studies to help us better understand the underlying disease mechanism and provide important evidence to develop disease prevention and management strategies for families, clinicians, and policymakers.

2021 Graduate Student Research Award winner Caren Cao

2021 Recipient, Bastable-Potts Graduate Student Research Award

Biography: Caren (Xiaoshu) Cao completed her HBSc and MASc as top students at University of Toronto, and is currently pursuing her PhD in Biomedical Engineering at University of Toronto. Her thesis work focuses on the discovery and treatment of novel physiological mechanisms of asthma worsening and its connection to obstructive sleep apnea, using advanced biomedical technology. Her previous work funded by Asthma Canada was recently published in the American Journal of Respiratory and Critical Care Medicine. She also has another publication related to aspects of her PhD work and four publications arising from her previous Masters thesis. She has already won four awards during the course of her PhD, including first prize in a national research competition. She has presented her research at six international and national conferences to date, including European Respiratory Society and World Sleep Congress. Caren’s work is highly innovative, focusing on understudied aspects of physiology at a time when asthma research has been focused primarily on pharmacological treatments. Caren hopes that this program of research could define an important new direction for the monitoring and treatment of asthma. If successful, it will also build new capacity for Canadian research in the application of new biomedical technologies for asthma management. 

Research Project: Understanding the link between obstructive sleep apnea (OSA) and asthma

Asthma and obstructive sleep apnea (OSA) are very common breathing disorders that cause disability and poor quality of life. Asthma and OSA often occur together but the reason for this remains unclear. Our research group has established that body fluid moving from the legs to the upper body during sleep is a cause of OSA. In previous studies, my colleagues showed that squeezing fluid out of the legs into the chest in asthmatics worsens their asthma by causing narrowing of their small airways. Therefore, I propose to investigate the possibility that OSA worsens asthma by increasing chest fluid volume overnight. Results from my previous research project funded by Asthma Canada showed that mimicking OSA draws fluid into the chest and increases small airway narrowing. This result provides strong evidence that one link between the two disorders is probably fluid moving into the chest. The second study will determine if asthma patients with OSA have more fluid moving into the chest and greater small airways narrowing overnight. The outcome of my research could lead to a novel approach to treating some cases of asthma: i.e. by diagnosing and treating co-existing OSA. Therefore, patients with poor asthma control may benefit from OSA screening. Ultimately, should my hypotheses prove correct, clinical trials could be designed to determine whether treatment of OSA can improve patient-centred outcomes over long time periods and reduce healthcare utilization.

Andrew Kouri

2021 Recipient, Bastable-Potts Graduate Student Research Award

Biography: Andrew Kouri is a respirologist and PhD student at the University of Toronto with an interest in airways diseases and how technology can be leveraged to improve the care of patients with asthma and COPD. His research investigates how mobile health tools are developed and used in older adults with airways disease, applying a health equity lens to the growing field of respiratory digital health. His academic goal is to become an  independent clinician-scientist and to study how best to deliver virtual and digital health technology to patients with asthma and COPD, including populations who are currently underserved by these promising health innovations. Outside of the hospital he loves cycling and running, hiking with his wife and lazy pug (and hopefully soon with his 2 month old newborn son!), and dreaming of future travels!

Research Project: My PhD research project is focused on trying to develop a deeper understanding of how mobile digital health tools like smartphone apps and electronic inhalers and other devices can be best used to help treat patients with asthma. I am particularly interested in how older patients use these type of tools, and how we can better design and implement mobile health technology in older patients with asthma. In order to accomplish this, I have studied specifically how older age influenced the use and engagement with a primary care mobile health asthma questionnaire developed at St. Michael’s Hospital by Dr. Samir Gupta, I am completing a literature review across all published studies of asthma mobile health to see how the needs of older adults have been considered (or not considered), and I am running a qualitative study where I am interviewing older adults with asthma in order to better understand their needs and unique perspectives when it comes to using mobile health technology.  

Samantha Lee

2021 Recipient, Goran-Enhorning Graduate Student Research Award

Biography: Samantha is a third year PhD student at the University of Manitoba in the Department of Biochemistry and Medical Genetics. Her research aims to clarify the molecular mechanisms underlying the developmental origins of childhood asthma using longitudinal DNA methylation microarray data from several human cohorts. In the past, Samantha has received support from the University of Manitoba Undergraduate Fellowship (UMGF), and she is currently completing her second year as a student in the competitive Visual and Automated Disease Analytics (VADA) graduate training program jointly hosted by the University of Manitoba and University of Victoria. In the future, Samantha hopes to apply her analytical skills in computational biology to improve the public health of Canadians. In her spare time, Samantha enjoys helping animals as a volunteer at the Winnipeg Humane Society.

Research Project: Prenatal air pollution exposure is associated with an increased risk of childhood asthma. While the mechanisms underlying this association remain unclear, researchers believe that environmental exposures become biologically embedded in epigenetic patterns during critical developmental periods. These altered patterns are thought to “reprogram” cell function, and ultimately influence health outcome. This research project will identify epigenetic patterns associated with prenatal air pollution exposure at birth and examine whether these patterns persist into childhood. Epigenetic changes will be correlated with childhood asthma to determine their role in asthma risk. However, we are most interested in the association between persistent epigenetics changes and asthma, as persistent epigenetics changes are more likely to influence health outcome than transient ones. This analysis will provide insight into molecular pathways that are altered by prenatal air pollution exposure and contribute to asthma. Additionally, as we believe air pollution induces epigenetics changes through increased oxidative stress, this research will investigate if maternal diets higher in antioxidants (like vitamin C) can mitigate the effect of prenatal air pollution exposure on child epigenetic patterns. Together, this research will help clarify how prenatal air pollution exposure predisposes children to asthma and begin identifying preventative measures.