Spinal cord injury (SCI) resulting from traumatic accidents is one of the most debilitating chronic conditions. In addition to the toll on quality of life, lifetime health care expenditures for these patients are among the most expensive of any medical condition, since many injuries occur in young patients who live with SCI for decades. SCI also comes with steep indirect costs, including morbidity due to chronic complications.
In individuals with SCI, bladder dysfunction and episodes of high blood pressure are two chronic conditions that present as significant clinical problems. Bladder dysfunction is commonly associated with a sudden, life threatening increase in blood pressure known as autonomic dysreflexia (AD). This episodic hypertension cannot be addressed with typical treatments, and if misdiagnosed or poorly managed can lead to myocardial infarction, stroke, and even death. Bladder dysfunctions and irritation such as a urinary tract infection are leading triggers for AD.
It is suspected that chronic exposure to AD episodes results in cerebrovascular damage in those with SCI. Chronically elevated blood pressure negatively impacts the brain and is specifically associated with cerebrovascular decline, altered brain morphology, cognitive dysfunctions and stroke in able-bodied individuals. However, identical pathologies are present in those with SCI.
Dr. Walter will investigate whether treating bladder dysfunction in patients with SCI will decrease possible triggers for episodes of AD, ameliorate its symptoms and consequently reduce chronic cardiovascular complications. Reducing the chronic cardio- and cerebrovascular complications of SCI would dramatically improve the health and wellbeing of patients with SCI and positively impact health care costs.
One in eight men in Canada will be diagnosed with prostate cancer in their lifetime. Despite the availability of surgical, radiological and drug treatment options, many patients develop castration resistant prostate cancer (CRPC), an incurable disease which is especially resistant to drugs. In its most lethal form, drug resistant CRPC behaves like a neuroendocrine cancer, which is completely unresponsive to traditional prostate cancer therapies.
In his model of drug resistant CRPC, Dr. Munuganti has identified a molecular pathway that appears to be essential for prostate cancer to take on neuroendocrine features. A key protein in this pathway, BRN2, is high in patients with neuroendocrine prostate cancer and is critical for neuroendocrine tumour growth in a laboratory model. BRN2 expression also plays a critical role in other neuroendocrine cancers such as small cell lung cancer and Ewing sarcoma. There is an urgent need to develop drugs that have the ability to inhibit the function of BRN2 for the treatment of patients with deadly neuroendocrine tumors.
Using high-powered and intelligently designed computer models, Dr. Munuganti has developed drug prototypes that have the ability to prevent BRN2 from supporting neuroendocrine cancer cell growth in our laboratory models. Dr. Munuganti’s study will fine-tune the drug-like properties of the leading BRN2 inhibitors and test them in biological models of neuroendocrine cancers. The results of this research could lead to the development of new therapies capable of reducing or slowing the growth of lethal neuroendocrine cancers, substantially improving patient survival.
Findings will be presented at conferences and seminars such as AACR Annual Meetings and the ASCO Annual Meeting, providing an opportunity to exchange ideas with other researchers and clinicians in the field and opening up possible collaborations. The ultimate goal of this study will be to commercialize a BRN2 inhibitor for patients suffering from no-cure neuroendocrine tumours.
Cardiovascular disease is the leading cause of death worldwide. Approximately 80% of all aneurysms that form within the aorta (the major blood vessel that deliveries oxygenated blood to the body) occur in the abdominal region. These are classified as abdominal aortic aneurysms (AAA). AAA is associated with progressive weakening and, ultimately, rupture of the vessel wall, causing rapid and extreme blood loss and a high rate of mortality. Sadly, aneurysm rupture is often the first sign of the disease and many die before reaching a hospital. For those that are diagnosed, treatment is currently limited to open chest or endovascular surgical repair. However, surgical repair of AAA is a risky, complex procedure with a high mortality rate.
In the past 40 years there has been a worldwide increase in forest fires. Although cigarette smoke is known to induce and advance AAA, the effect of wood smoke on blood vessel remodelling and AAA is currently unknown. Interestingly, firefighters are at a four times greater risk for having a heart attack compared to other emergency response personnel. In fact, firefighters are at a greater risk of dying from cardiovascular disease than from on the job burn injury. Although smoke exposure is thought to play a major role in the majority of firefighter cardiovascular deaths, the processes by which wood smoke may promote cardiovascular disease and AAA is unknown.
Granzyme B (GzmB) is an enzyme that breaks down the protein-based scaffolding between cells that is important in sustaining tissue structure and function. Human and mouse models of AAA have shown that GzmB expression is increased within the blood vessel wall of aneurysms and its degree of expression is directly related with aneurysm rupture. In animal models, drugs that inhibit of GzmB prevent aneurysm rupture and increase survival. Although cigarette smoke is associated with increased GzmB levels in those with lung disease such as COPD, the link between wood smoke, GzmB and AAA is not known.
Dr. Zeglinski will examine the effect of repeated exposure to wood smoke on GzmB expression in the vessel wall and its effect on AAA progression. To explore this relationship, he will use a well-established mouse model of AAA and determine what, if any, effect that wood smoke has on aneurysm formation and rupture.
The results of this research could lead to the development of new drugs to treat AAA, a devastating disease with few treatment options. Should the results confirm that GzmB is involved in AAA, Dr. Zeglinski will team up with clinicians for a clinical study to assess the levels of GzmB in those who have been diagnosed or have died from an AAA. By translating findings from the bench to the clinic, Dr. Zeglinski will later be able to partner with drug companies to develop a novel therapeutic agent to block GzmB action to slow or stop the progression of AAA and prevent AAA ruptures.
Patients with Inflammatory Bowel Disease (IBD) suffer bouts of extreme gut inflammation that disrupt the population of bacteria in their intestines. Consequently, IBD patients often have fewer beneficial bacteria and suffer an overgrowth of potentially dangerous bacteria. In healthy individuals, such responses are typically prevented by SIGIRR, a protein made by the cells that line the gut.
SIGIRR acts by suppressing mechanisms that drive inflammation. Loss of SIGIRR dramatically increases inflammation and drives bacterial imbalance. The inflammation can become so severe that gut tissue can become necrotic. Currently, there is no way to promote the beneficial actions of SIGIRR in the gut. Recently, however, a newly recognized anti-inflammatory compound called interleukin (IL)-37 has been shown to interact with SIGIRR to inhibit inflammatory responses in human cells.
Dr. Allaire will test whether IL-37 stimulates SIGIRR to: control inflammation and suppress bacterial killing responses in the cells that line the gut; protect mice from experimentally-induced IBD; and promote normal gut microbe balance. Results from this study will include an evaluation of the potential for IL-37 to act as a new therapeutic for patients with IBD.
Recent debates about palliative end-of-life (EOL) care and legalized assisted dying have stimulated new questions about EOL care for those living with dementia. However, when discussing preferences for EOL care, individuals with dementia are often excluded from the decision-making process, leaving decision making to family members and/or care providers.
With growing numbers of people living with dementia, it is imperative to understand what they envision for their EOL care. While some research suggests they are able to discuss their preferences for care, there is a significant gap in understanding what people with dementia envision for their own EOL care and how they and their family members share in the decision-making process.
Utilizing a critical narrative approach that employs in-depth interviews, visioning workshops, visual arts and storytelling, Dr. Puurveen will examine the EOL preferences and shared decision-making processes of people living with dementia and their family members. Her study will explore:
- How people with dementia and their family engage in shared EOL decision-making.
- The kinds of decisions that they make regarding future care.
- How the age, gender, race, and relationships of individuals with dementia and their families, as well as larger socio-political factors such as legalized assisted dying, influence EOL decision-making.
- What people with dementia identify as an important message about EOL care that can be shared with the public.
To provide an opportunity for conversation beyond those immediately involved in the research, a public art exhibition will be held at a local gallery that invites members of the public, care providers and policy makers to view the art created at the visioning workshops and reflect upon living well with dementia to the end of life.
Dr. Puurveen’s findings will generate practice and policy recommendations for improving EOL decision-making (e.g., advance care planning), that will in turn help improve the quality of care of individuals with dementia and their quality of life at the EOL.
Heart failure (HF) is a progressive condition wherein the heart is unable to fill its chambers and/or pump sufficient blood into the arteries. While there are many causes of HF, it usually presents in two major forms: HF with preserved ejection fraction (HFpEF; ‘stiff’ heart), and HF with reduced ejection fraction (HFrEF; ‘baggy’ or ‘weak’ heart).
A key challenge in HF diagnosis is that, while the causes of HFpEF and HFrEF differ, their clinical presentation is often the same. As a routine echocardiogram in HFpEF can appear normal, the diagnosis can be overlooked and delayed. In clinical practice, the diagnosis of HF is often made late, at which time evidence-based treatments or other lifestyle strategies may have less benefit for those with HFrEF. At the same time, many HFpEF patients are being treated with drugs that provide no proven benefit.
Dr. Singh will investigate novel, non-invasive diagnostic approaches that can identify patients with HFpEF versus HFrEF at an early stage of disease. The results of this research will include innovative methods for data integration and biomarker discovery, which will improve biological insights into the mechanisms of HF. Identifying the form of HF earlier on will allow clinicians to develop and tailor diagnostic and therapeutic approaches, and use a firm diagnosis as a tool to encourage lifestyle changes.
Diagnosis of HFpEF versus HFrEF will ensure that the most appropriate additional tests and treatments can be provided for each patient in a timely fashion, improving disease management and patient quality of life.
With every heartbeat, one quarter of all the blood in the body flows through the brain. This activity is essential for the health of neurons in the brain throughout life. Although scientists realize that understanding how to keep blood vessels in the brain healthy may offer new ways to treat brain disorders including Alzheimer’s Disease, a big challenge facing this area of inquiry is the lack of methods available to study the brain’s blood vessels outside of an animal model, which do not always mimic the human condition closely enough to provide answers that help to develop effective treatments for brain disorders.
Dr. Robert has to date made considerable progress in being able to grow functional, three-dimensional and human-derived cerebral blood vessels in vitro using tissue engineering technology, and has used these vessels to analyze the accumulation of beta-amyloid peptide, which is a pathological hallmark of Alzheimer’s disease.
The primary goal of Dr. Robert’s research, in collaboration with the Canadian Consortium of Neurodegeneration and Aging , is to use this novel platform to better understand how blood and brain lipoproteins affect human cerebral vessel health.
Although lipoproteins are traditionally known for their roles in carrying fats through aqueous body fluids, recent research has revealed that lipoproteins also influence inflammatory pathways and cellular signalling. Importantly, the composition of human lipoproteins are very different than their murine counterparts, and so far existing neurodegenerative disease mouse models have not been able to accurately model these differences.
Dr. Robert’s innovative platform allows for mechanistic studies in a fully human experimental system. As such, the major translational plan for this research will be to disseminate findings to the academic and clinical communities through publication and presentations. As Dr. Robert’s methods use many technologies already established in cardiovascular medicine, the results will also be of significant interest to the medical and research communities and drive accelerated progress toward understanding the contribution of cerebrovascular dysfunction to dementia.
In Canada, a striking 13% of children (~500,000) have asthma. It is the leading cause of absenteeism from school, and accounts for more than 30% of Canadian health care billings for children. Asthma is also the leading cause of hospital admissions in both children and the general Canadian population. Given that asthma typically begins in childhood and lasts throughout life, the high prevalence, combined with significant related morbidity, make asthma the most common and burdensome chronic non-communicable disease affecting young Canadians.
Asthma is a complex disease dependent on the interactions of genetic predisposition with environmental factors including physical, microbial, and social environments. The Canadian Healthy Longitudinal Development (CHlLD), a cohort study funded by CIHR, has recruited over 3,500 pregnant mothers to collect such environmental and biological data from pregnancy up to age five in four Canadian cities: Vancouver, Edmonton, Toronto and Winnipeg. The proposed project will use biological and environmental data from the CHILD cohort and will focus on traffic-related air pollution and natural spaces. These two modifiable environmental exposures have been shown to be associated with asthma exacerbation.
The novelty of this research lies in the study of joint exposures and their interactions over time; their impact likely depends not only on individual genetic profiles, but also on the critical timing of exposure. Early life period, including in utero, is a critical influence on health in later life. Likewise, changes in gene function in relation to environmental influences provide evidence to explain how and why asthma and allergies exist and progress.
Dr. Sbihi’s research will examine how these changes, called epigenetic modifications, are affected by the early-life environmental exposures, including the body’s microbial milieu. By examining how the environmental exposures (traffic air pollutants, natural spaces, gut microbes) impact DNA methylation and consequently how these epigenetics modifications lead to asthma, we will be able to better understand the mechanisms of asthma development and subsequently provide better targeted prevention measures.
Type 2 diabetes (T2D) is a chronic disease with serious health implications (e.g., cardiovascular disease) that can be prevented with lifestyle changes. Lifestyle-based interventions are particularly needed in the community to help reduce the incidence of chronic disease in Canadian adults, and are critical for preventing T2D.
For example, the Diabetes Prevention Program (DPP) is a lifestyle change program that promotes healthy eating and physical activity. This program translates to a 58% risk reduction for developing T2D for individuals who maintain 150 min/week of moderate physical activity and lose 7% of their body weight. However, the DPP is less sustainable in community settings because it is costly and lengthy (~12 months long). Diabetes prevention programs are needed that can be implemented and scaled up in the community for adults at high risk of developing T2D.
Towards the pursuit of preventing T2D with brief-behavioural interventions, the Health and Exercise Psychology Laboratory at UBC Okanagan developed a diabetes prevention program called Small Steps for Big Changes, which has proven effective in enhancing health outcomes of low-active adults at risk for diabetes and, excitingly, demonstrates long-term physical activity adherence.
Given the promising findings, knowledge translation research is needed to ensure successful research uptake of Small Steps for Big Changes into the community. The aim of Dr. Ivanova’s research will be to translate this evidence-based exercise intervention for use in the community with adults who are at risk for T2D.
Small Steps for Big Changes will be implemented in a YMCA centre (Kelowna, BC) to ensure that this evidence-based program is integrated in a sustainable manner and that it adequately serves the community. The Knowledge-to-Action (KtA) framework will be used to guide this knowledge translation effort, and the results of this research will be the development of knowledge products, namely manuals for Small Steps for Big Changes, a two-day train-the-trainer workshop, and audiovisual training materials that will be used to train the knowledge users how to deliver Small Steps for Big Changes.
Dr. Ivanova will co-lead the sharing of these results, alongside research end users, guiding the path for sustained use of Small Steps for Big Changes at the YMCA and for feasible continued scale-up.
Early intervention therapy (EIT) programs for children with developmental challenges and disabilities have been shown to be highly beneficial for young children (0-5 years) in the wider Canadian population. However, EIT programs are consistently significantly under-utilized by Indigenous communities and families. Indigenous parents and community stakeholder perspectives on EIT are largely absent in current literature, and Indigenous communities are often not consulted on how these programs are delivered.
Dr. Gerlach’s research will generate new knowledge aimed at improving the health, development, and quality of life of Indigenous children with developmental challenges and disabilities. The research will take place in northern BC, where there are a large number of rural/remote First Nations and urban Indigenous communities. This study builds on Dr. Gerlach’s extensive experience working with Indigenous communities, organizations, and families as an early intervention occupational therapist and community researcher. The methodology has been developed in close collaboration with research impact partners, including community stakeholders, the First Nations Health Authority, the Ministry of Children & Family Development, and child development centers in the northern region.
A local Indigenous advisory circle will be formed to guide the research process, and sources such as policy documents and interviews with key policy stakeholders will provide insight into how funding, policy, and organizational factors influence Indigenous parents and children’s access to and use of EIT services. The results of Dr. Gerlach’s research will inform the creation of EIT practices and policies that are responsive to the realities, strengths, and needs of Indigenous families and children living in rural and remote communities in northern BC. The findings will also be shared with a wide audience through community forums, policy briefs, and publications.
This research has national and international relevance at practice and policy levels. BC has an opportunity to take a leadership role in this emerging field of research and in the implementation of Jordan’s Principle, which is focused on achieving health equity for all Indigenous children regardless of where they live.
