A spinal cord injury (SCI) is defined as damage to the spinal cord that results from traumatic (e.g. motor vehicle accidents or falls) or non-traumatic (e.g. spina bifida or tumour diagnosis) causes. Children with SCI often require extensive medical follow-up and rehabilitation, and are at increased risk of adverse health effects (such as bladder issues, respiratory and cardiovascular disorders, and death) compared to children without SCI. Despite presumed increases in the number of Canadian children living with SCI over time, little is actually known about paediatric SCI in Canada. Using electronic health data from British Columbia and Ontario and health analytics, my proposed research aims to address existing SCI knowledge gaps by 1) developing national case definitions for traumatic and non-traumatic paediatric SCI, 2) estimating the number of Canadian children living with SCI, and 3) increasing understanding of long-term health outcomes and healthcare utilization among children with SCI. Findings from this research will, for the first time, describe paediatric SCI in Canada, identify paediatric populations most at risk of SCI, and identify opportunities to improve paediatric SCI care in British Columbia and across Canada.
Year: 2021
The effect of temperature on brain bioenergetic stress in hypoxia
Cooling the brain is a therapeutic strategy to protect it from stress. The long-held belief is that cooling the brain reduces its activity — and thus its need for oxygen — thereby tilting a favourable balance of oxygen supply and demand. However, recent data from our lab challenges this paradigm. We have shown that brain blood flow is reduced by whole-body cooling, and this dramatically impairs oxygen supply to the brain. Therefore, it is important to know exactly how much the brain’s activity is reduced so that we can determine whether the balance of oxygen supply and demand is improved or further disrupted. Surprisingly, this is unknown in the human brain. Our objective is determine how the brain’s oxygen supply and demand is affected by cooling and heating, and how this impacts its resilience to stress. We will heat and cool healthy human subjects and expose them to low oxygen, whilst measuring markers of brain stress. We will then collect the same markers of brain stress in patients with brain injury before, during and after therapeutic cooling. Together, these studies will expose how temperature affects the brain’s resilience to stress and provide rationale for how best to harness the cold to protect the brain.
Immigrants, work and health: Evaluation of services to reduce inequities
Work is a marker of successful integration for immigrants to Canada. While we know much about the health outcomes and employment patterns of immigrants within the Canadian context, less is known about the impact of work on health, in particular on work disability experiences. Emerging evidence suggests that immigrants take longer to return to work following a work injury/illness compared to Canadian-born workers. Provision of employment-related and rehabilitation services are meant to provide access to safe work and minimize work disability but, this has not been examined in immigrant populations. Using a unique research opportunity that will merge immigration data with 1) workers’ compensation and medical services data; and 2) settlement service use for the working population of British Columbia, the purpose of this study is to examine the impact of rehabilitation and employment-related services on work and work disability experiences of immigrants compared to Canadian-born workers, along the continuum from injury to rehabilitation to return to work and income earning. Evidence of different experiences and effectiveness of services can inform best practices and reduce health inequities for all workers, including immigrants.
Impact of prostate cancer subtypes on bone remodeling and microarchitecture in metastatic lesions of the spine: A combined cellular, genetic and mineralization study
One in nine men will develop prostate cancer (PC) in their lifetime. Although modern therapies have increased the survival rate, almost all advanced cases will metastasize to bone, with the axial skeleton being the most frequent location. Bone metastases (BM) are the most severe complications of PC generating severe pain, fractures, and spinal cord compression. So far, it is not clear how PC BM are related to pain and fracture. Most cancers that generate bone complications, are associated with bone loss. However, PC is associated with bone formation. The aims of this project are to understand the structure of this new formed bone, how prostate cancer cells induce these changes, and if there are any specific types of PC associated with these changes. The ultimate goal is improving disease management and preventing complications of PC BM.
I have observed the microstructure structure of PC BM in mineral and protein content. Also, I have identified different types of PC cells in the PC BM, meaning the cells are undergoing a transformation process in the bone. These results are unprecedented, and my aim is now to expand the sample size and to explore the structure of PC BM in greater detail in order to prevent its severe consequences.
Investigating sex differences in dyspnea across the spectrum of chronic obstructive pulmonary disease severity
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.
Programming bordetella pertussis to produce novel vaccines
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.
Can we identify dementia risk from 24-hour wrist-worn actigraphy? Using machine learning to identify risk factors for dementia during the 24-hour day
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.
Endothelial calcium dynamics regulating cerebrovascular function and capillary stalling in the healthy and diabetic brain
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.
Honouring all our relations: Advancing health and wellness of uncounted Indigenous peoples in BC through addressing gaps in population health and wellness reporting
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 role of mechanics in EMT and cancer metastasis
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.