Chronic obstructive pulmonary disease (COPD) results in breathlessness, reduced activity level and quality of life. The number of women with COPD in BC is increasing. Healthy women experience more breathlessness during exercise compared to men. Women with mild COPD experience even more breathlessness and report worse quality of life. The basis for sex differences in breathlessness across the full spectrum of COPD disease severity has not been studied and is the main focus of our proposed research.
We will explore how breathlessness differs between women and men with mild-to-severe COPD in a group of patients that undergo lung function testing and specialized exercise testing as well as using data from a Canadian cohort study of COPD patients. We will also use high resolution imaging of the lungs to relate structural changes due to COPD to the symptoms women experience.
This is the first study to explore sex differences in breathlessness across COPD disease severity from two perspectives, using detailed exercise tests and a complementary COPD database. Understanding breathlessness in women with COPD is a first step in order to develop effective treatment strategies for the increased symptoms women experience.
Pertussis (whooping cough) continues to be a problem despite high vaccination coverage against Bordetella pertussis, the bacterium that causes the disease. Annually, there are 24 million cases of pertussis and ~160,700 deaths worldwide. Pertussis is a respiratory disease that is transmitted from person to person through airborne droplets and poses a threat to unvaccinated infants and children whose immunity has dropped. Currently, there are two forms of the vaccine in use. The first is the killed whole-cell vaccine (wP), which is effective, but has side-effects such as swelling at the site of injection and fever. These adverse effects have diminished its acceptance in high-income countries and led to its replacement by the acellular vaccine (aP) that only contains purified components of the organism. While the aP vaccine protects against getting pertussis, it does not prevent transmission of the disease and fails to provide long-term immunity.
We aim to develop two new vaccine candidates: a revised wP and a novel aP to control the re-emergence of pertussis. This will be done through modifying some of the structural components of the bacteria to either alleviate the side effects or overcome the deficiencies of the wP and aP vaccines.
By 2031, there will be a projected 674,000 Canadians living with dementia. Early detection of dementia risk will thus be critical to reducing dementia prevalence. Circadian rhythms (i.e. the ~24-hour biological clock) are critical to the maintenance of the sleep-wake cycle, and sleep-wake disturbances are common in people at risk for and living with dementia. Several studies have identified circadian risk factors for cognitive decline and dementia using wrist-worn actigraphy (a common field measure for indexing the sleep-wake cycle of circadian rhythms). However, there are opportunities to use the power of artificial intelligence, specifically machine learning (ML), to enhance the sensitivity and specificity of wrist-worn actigraphy (WWA) for detecting sleep-wake cycle disturbances which are associated with increased dementia risk. Thus, I will use ML and WWA data from the UK Biobank (90,000+ participants with valid data) to identify risk factors for dementia from the 24-hour sleep-wake cycle. The results of my project may provide a non-invasive and sensitive method to identify patients at greater risk for cognitive decline and dementia.
The brain is a metabolically demanding organ . Mismatch between blood flow and demand (from neurons) leads to a disruption and in extreme cases injury. Because the smallest blood vessels in the brain are narrow, they are prone to becoming obstructed by circulating cells and debris. This is exacerbated in Diabetics, with “sticky” blood vessels. The cells of blood vessels, endothelial cells, are more than just “pipes”, they form large physically connected networks between themselves. An important regulator of these networks, and a signal to communicate between them, is waves of calcium flowing into cells, which can propagate between these cells. How Diabetes affects these networks of blood vessels, and in turn impact the health of the brain is unknown. Thanks to new genetic tools with state of the art microscopes, we can directly observe these calcium fluxes into endothelial cells in the living, awake, mouse brain, and especially when these blood vessels become occluded. Combined with simultaneous monitoring of blood flow and neural activity I will be able to directly measure concurrent changes in brain activity, blood flow and calcium fluxes to investigate these dynamics in the living healthy or Diabetic mammalian brain.
Reporting on population health is important to monitor trends, identify priorities, and track progress to address inequities. All Indigenous peoples have the right to be counted. Yet, over 88,000 Indigenous people in British Columbia (BC) who do not have ‘Status’ under the Indian Act or are not registered with Metis Nation BC are currently ‘uncounted’ in population health reporting.
Responsibility for reporting on health of BC residents lies with the Office of the Provincial Health Officer, including collaborative reporting on health of diverse Indigenous peoples in BC. Currently, there is no process to report on health of uncounted Indigenous peoples. Gaps include: lack of formal relationships with those representing uncounted Indigenous peoples; no way of identifying this population in BC health data; absence of research frameworks reflecting uncounted Indigenous peoples’ perspectives; and no implementation plan for province-wide surveillance involving uncounted Indigenous peoples.
This study aims to support health of uncounted Indigenous peoples in BC by addressing current gaps in population health reporting, through partnerships that uphold Indigenous self-determination, decision-making and perspectives of health and wellness.
The World Health Organization reports that cancer is the second leading cause of death globally, responsible for 1 in every 6 deaths. This ratio doubles in Canada, with the Canadian Cancer Society estimating that nearly 1 in 2 Canadians will develop cancer, and about 1 out of 4 will die from it.
Recent anticancer therapies target the epithelial-to-mesenchymal transition (EMT), a process that converts tightly bound cells into loosely associated motile cells. In cancers, this results in progression with metastasis and improved resistance to treatments.
Evidence shows the role of mechanics in driving EMT but how the biochemistry and the mechanics coregulate this process remains largely unknown.
We propose to investigate this question in the case study of stem cell cultures, which undergo EMT in a controlled environment. We will develop a mathematical model to link mechanical stresses and cytoskeletal energetics, and we will validate it experimentally in collaboration with the Zandstra Lab.
This proposal will enhance BC’s and Canada’s leadership in healthcare-oriented research, as understanding EMT is essential not only for cancer but also for many other biological processes, such as organogenesis and tissue regeneration.
T cells are an important component of our body’s adaptive immune system, helping to identify and overcome diverse diseases. An emerging treatment for cancer, viral infections, and other diseases is to engineer patient’s T cells to recognize and respond to diseased cells. However, because of the reliance on patient-derived T cells, such treatments are highly expensive. To lower costs and increase accessibility to T cell therapies, our laboratory is developing methods to generate T cells from an unlimited and readily-available source: human pluripotent stem cells. Pluripotent stem cells give rise to every cell in our bodies, including T cells, and can be grown indefinitely in laboratory settings. Our current process for producing T cells from stem cells has made great progress, but lacks control over key parameters such as whether the T cells will become “helper” cells that stimulate the immune system or “cytotoxic” cells that directly kill diseased cells, and if they will provide long-term memory or have strong, short-term effects. In this project, I will genetically engineer stem cells such that we can produce T cells with these diverse properties on-demand, thereby enabling the next generation of off-the-shelf T cell therapies.
Platelet cells are routinely transfused during treatment of a range of conditions, due to their specialized roles in hemostasis. Despite the significant potential to enhance the efficacy and applicability of platelet transfusions, no techniques have yet been developed to engineer modified platelets. mRNA therapeutics is a promising novel class of nanomedicine with broad clinical applicability, capable of enhancing the physiological function of target cells by modifying cellular protein expression. The therapeutic potential of mRNA editing is particularly relevant to transfusion science, where the mechanisms of delivery to patients are well established. By engineering platelets using gold standard mRNA transfection strategies, their therapeutic potential can be maximized for diverse applications.
Engineered platelets will be created using cutting-edge mRNA lipid nanoparticles. Successful mRNA editing will create platelets with enhanced biochemistry and improved hemostatic function. Results generated from this project will address knowledge gaps in platelet translation mechanism, and guide forthcoming research on the next generation of blood products, improving current standards of care in blood transfusion.
Loneliness is becoming increasingly recognized as a serious threat to mental health. Social isolation is detrimental to adult brain function and behavior across mammalian species. Chronic social isolation in rodents has been found to lead to depression-, anxiety-, and psychosis-like behaviors as well as signs of abnormal locomotor habituation, fear responses and aggression. However, our understanding of how and why social isolation is risky for health — or conversely — how and why social ties and relationships are protective of health, remains quite limited. Our lab makes use of advanced brain imaging and recording techniques to map connections between brain areas. We plan to use these techniques to help us to first understand the neuropsychiatric basis of chronic social isolation in animal models. A machine learning algorithm will be used to classify large behavior datasets automatically and objectively, and potentially uncover new pathological behavioral patterns that have been overlooked by human observers. Mapping large-scale brain functional connectivity associated with social isolation–induced behavioral deficits may shed light on the etiopathogenesis of mental disorders and lead to the identification of therapeutic targets.
Physical activity plays a key role in maintaining a healthy lifestyle. However, approximately 7% of Canadians live with a mobility impairment, decreasing their ability to participate in daily activities and subsequently increasing their time spent in sedentary behaviours (sitting). Living a sedentary lifestyle is associated with poor health and risk of cardiovascular disease, particularly in those with a compromised health.
In the elderly, chair-based exercises are shown to improve mobility function and quality of life, with general compliance shown to be better than standing or dynamic exercises. During the current COVID-19 pandemic, there is limited access to group activities and therapies due to social distancing requirements. Therefore, telehealth (videocall) delivery of exercise interventions is of great importance in helping to maintain a healthy lifestyle. Our project will investigate the effect of delivering a telehealth chair-based exercise intervention on motor function in stroke survivors with a mobility impairment (unable to walk without assistance of one person). Secondary outcomes include balance and quality of life. The results can help develop telehealth interventions that can be delivered in rural communities.
