With the highest rates of premature mortality at 3.71/1,000 people, the Northern Health Authority has the lowest health status in BC. Dr. Sarah de Leeuw’s research seeks to address this issue by examining how creative arts and the humanities can help resolve health inequities experienced by Indigenous and non-Indigenous people in northern BC.
To do this, she will draw on her previous research as well as growing global evidence that shows how medical humanities and health-based creative arts can enhance well-being. She will also look at how social determinants of health frameworks can explain health disparities.
She will lead a team of northern BC community advisors, health researchers, and medical/health science students. The team will develop and deploy multi-disciplinary creative methods and methodologies to harness, document, translate, and disseminate existing northern strengths – especially First Nations’ – as a population health and wellness initiative.
Her research will:
- Advance new methods, approaches, and models – anchored in creative arts and social determinants of health frameworks – that produce and translate innovative ways of addressing health inequities.
- Promote rural, northern and First Nations communities through the creative arts as places where health service providers want to live and work.
- Use creative arts to increase interest by locals – particularly First Nations – to pursue health and medical education and training within the region and to then stay in the region.
- Encourage multi-disciplinary cross-community collaborations.
- Augment northern health education curricula (nursing, social work, medicine, community health) with accessible, targeted, and affecting knowledge.
- Circulate strengths-based evidence about populations in the Northern Health Authority – especially First Nations – beyond the borders of the health authority with the intent of encouraging southern, urban, and non-Indigenous British Columbians to feel vested in the wellness of BC’s northern populations.
Next-generation sequencing (NGS) is the automation of high-throughput DNA sequencing on a massive scale that is rapidly transforming biology and medicine. It can enable laboratories to detect small, but clinically significant, numbers of drug-resistant viruses in blood samples from infected individuals.
The lack of computational tools to process and interpret NGS data collected from rapidly-evolving populations such as HIV remains a major obstacle in the application of NGS to HIV treatment and prevention. Dr. Poon’s research will bridge this divide by developing computational methods for NGS analysis designed to address key issues in HIV prevention and treatment. He will share his software as a free resource to the basic and clinical research communities.
He will take advantage of resources available to him through the BC Centre for Excellence in HIV/AIDS (BC-CfE): an extensive archive of HIV plasma specimens; one of the world’s few NGS cores dedicated to HIV research; and his own expertise in molecular evolution and bioinformatic sequence analysis.
As part of his research, he is developing and validating a new method to reconstruct the time of HIV infection from NGS data. Using specimens from the BC-CfE, he will estimate times of HIV infection and reconstruct the historical trend of HIV incidence (the rate of new HIV infections) in BC. This will help assess the long-term impact of expanding access to HIV therapy in BC and identify other correlates of HIV incidence.
He will also use “phylogenetic” methods, which can infer the ancestral tree that relates observed genetic sequences, to reconstruct the history of HIV transmissions in BC. This will allow him to evaluate the impact of expanding access to HIV therapy in BC on the rate of transmitting drug-resistant HIV, and to characterize the variation in rates of HIV transmission over the course of the epidemic.
Finally, he will develop a new class of methods for analyzing NGS data to characterize the adaptation of HIV to the host-specific immune response, and to reconstruct the genetic sequence of the transmitted HIV strain. The results from these methods can provide key information for the development of HIV vaccine candidates – a core aim of HIV prevention research.
Osteoarthritis is one of the leading causes of physical disability in adults worldwide and is associated with a significant personal and economic burden. It is estimated that one in eight Canadian adults currently have osteoarthritis, which results in $10.2 billion in annual health-care costs and an additional $17.3 billion in economic impact due to loss of employment productivity and other indirect health-care costs. Most commonly affecting the knee, osteoarthritis is characterized by the breakdown of articular cartilage, a smooth lining at the ends of bones that allows ease of movement and shock absorption. It is believed that high magnitude and poorly distributed loads that pass through the knee joint play a strong role in the development and progression of knee osteoarthritis. Improvements in pain, physical function, and quality of life can be achieved by developing treatments that effectively reduce and more evenly distribute these loads.
Dr. Michael Hunt’s research will focus on the use of sophisticated motion analysis equipment and techniques as a way to measure the loads experienced by the knee joint during walking. A better understanding of the factors that influence the magnitude and distribution of knee joint load will inform the development of treatment methods that effectively target these factors. He will focus on methods to optimize the load-reducing capacity and methods of clinical delivery of three treatments: lower limb exercises, gait modification, and shoe insoles. These treatments are designed to be non-invasive (non-surgical and non-pharmacological) in order to improve patient safety while minimizing health-care costs.
This research will be the only program in BC (and one of only a few in Canada) using analysis of motion and knee joint loading to inform clinical treatment for knee osteoarthritis. The focus on non-invasive treatments is in stark contrast to the majority of current osteoarthritis research, which is in the areas of surgery or drugs. Hunt’s research will provide effective treatment alternatives that have lower costs of delivery, fewer side-effects, and wider availability to patients. In addition, new treatment strategies that minimize joint loads have great potential in slowing the rate of disease progression, thereby reducing economic costs in the long-term and significantly improving the quality of life of those affected.
Individuals 65 years of age and older constitute the fastest growing age group in Canada. With natural adult aging, the neuromuscular system (the muscles of the body and the nerves that supply them) undergo degenerative changes that are characterized by reductions in strength and power due to decreased muscle size. This age-related muscle weakness and overall decline in muscle function is referred to as sarcopenia. Sarcopenia not only interferes with tasks as lifting and carrying groceries, navigating stairs, and performing smooth complex movements, it is highly linked to physical disabilities and risk of falls. Sarcopenia is caused by a decrease in the number and function of motor units (MU), which consists of a single nerve branch and all of the muscle fibres it supplies. During the aging process, some of the MUs die off, while other MUs change structurally to compensate. As a result, there are fewer MUs present, but each one supports more muscle fibers. This MU remodeling process is a compensatory mechanism that acts to maintain muscle strength until a critical threshold is reached and strength decreases at an accelerated rate, usually by the eighth decade of life.
To understand the underlying biological mechanisms of MU remodeling, Dr. Brian Dalton is using a technique called single-unit microneurography. This research tool uses tiny electrodes inserted through the skin and into a peripheral nerve to stimulate and record signals from individual MUs. Using this technique, he will measure the integrity of functioning MUs in aged adult volunteers to determine if MU remodeling impairs neuromuscular function and muscle performance in the older adult. This work will help build a more comprehensive understanding of the neuromuscular system, specifically the process of sarcopenia and how it impacts natural adult human aging. The information gained from this study will aid in the design of functional training programs to improve and maintain muscle function — and quality of life — in older adults.
Diabetics are two to four times more likely than non-diabetics to suffer a stroke during their lifetime, and their prognosis for recovery from stroke is poor. Diabetes is known to negatively affect blood vessels throughout the body, including the eye, heart, kidney, and limbs, leading to a heightened risk of stroke in diabetics. Poor circulation and peripheral nerve damage can lead to blindness, hearing loss, foot injury and amputation. High blood pressure is common in diabetics and increases the risk of heart disease and stroke. However, little is known about how the vascular changes associated with diabetes affect the brain and contribute to poorer recovery of function following stroke.
Dr. Kelly Tennant's research will determine why diabetics suffer from greater impairments following strokes. She will monitor changes in neurons and blood vessels over time following a stroke in diabetic mice and assess the relationship between these changes and recovered use of the forelimb. Dr. Tennant will employ cutting edge in vivo imaging technologies such as intrinsic optical signal, two-photon, and voltage sensitive dye imaging, combined with behavioural testing of forelimb function.
These experiments will shed light on how neurons and blood vessels of diabetics respond differently to ischemic stroke and how these differences contribute to poor behavioural recovery in diabetic stroke survivors. This research will aid understanding of the greater impairment caused by stroke in diabetic patients and lead towards development of treatments that ameliorate the negative effects of diabetes on the brain.
The cilium is an extension on most cells and tissues that works similarly to a television antenna, in that it receives signals from the environment. When a mutation disrupts the function of cilia, cells no longer receive the proper environmental input. Mutations in cilia proteins have been identified in patients with clinical ailments such as blindness, obesity, diabetes and polycystic kidney disease; some are also found in syndromes encompassing all or most of these disorders. Although some of these syndromes affect entire families, the molecular and cellular causes of these disorders have not been identified or characterized; for this reason there are no therapies available. Dr. Victor Jensen aims to study and identify novel cilia genes that are associated with multiple disorders, including blindness and obesity. These results will provide essential information about the association between disease and different genes, as well as the function of cilia. This unique approach to gene discovery and characterization was developed in the laboratory of Dr. Leroux, and has already led to the discovery and understanding of numerous disease genes, including those associated with the multi-systemic Bardet-Biedl syndrome. Dr. Jensen’s research work is therefore aimed at providing novel insights into the nature and function of disease genes, a step that will eventually lead to improved treatments or prevention of common human medical ailments.
Asthma patients are at risk of potentially severe and sometimes lethal exacerbations. These exacerbations can be caused by a variety of triggers, such as infections or exposure to allergens. Diesel exhaust and other traffic-related constituents can also be inhaled along with the allergen. This multi-inhalant mixture results in immune reactions that are more complex than exposure to the allergen alone. Although it is well established that multi-inhalant mixtures of allergens and pollution contribute to asthma exacerbations, research in this area typically focuses on exposures to single agents, either diesel exhaust or allergens alone.
Dr. Francesco Sava is investigating the relationship and the synergies that exist between diesel exhaust and allergen-triggered asthma exacerbations using a live-patient model. His aim is to demonstrate that inhalation of diesel exhaust increases allergen-induced inflammation in the lungs of asthmatic patients. Using state-of-the-art equipment, he will expose patients to controlled diesel exhaust concentrations. A very small amount of allergen will be introduced into a segment of the patients’ lungs, and the resulting inflammation will be measured. This multi-inhalant exposure model reflects the real-life conditions that patients are likely to encounter. The experimental model he uses has been widely studied, is very safe, and allows researchers to test allergens on humans without triggering an overt asthma attack.
The research will help define the synergies between the real-world concentrations of inhaled diesel exhaust and allergen exposure in the asthmatic population. This information will likely lead to recommendations for air quality and strategies to protect vulnerable populations.
Lung cancer is one of the largest health burdens worldwide: in Canada alone, lung cancer causes more cancer-related deaths than breast, colon, and prostate cancers combined. Smoking cessation programs have been highly successful, and the population of former smokers in Canada is well over seven million. Unfortunately, while quitting smoking is a proactive step, former smokers are still at risk for developing lung cancer. This cancer risk in former smokers will remain one of Canada’s most significant health concerns for the next 50 years. The molecular mechanisms responsible for the development of lung cancer in former smokers are not known. Recent studies have shown that although the majority of smoking-induced genetic damage returns to normal after smoking cessation, some genes are permanently damaged and never return to the pre-smoking state. Some of these irreversible genes are likely those that act as the gatekeepers for cancer development. Dr. Ewan Gibb’s research project will identify the genes in former smokers which do not return to normal after smoking cessation. He will be using integrative genomics to compare samples from former smokers with cancer and those without. This information will help Dr. Gibb understand why some former smokers go on to develop lung cancer while others remain cancer-free despite similar changes in lifestyle. This set of irreversibly damaged genes can serve as novel targets for anticancer therapies or may be developed as diagnostic markers for early detection of lung cancer while therapies are still effective.
Stroke is the leading cause of neurological disability in Canada. Most stroke survivors have a number of other related conditions, including heart disease, diabetes, obesity and high blood pressure, which contribute to their risk of additional strokes. Exercise not only improves fitness, it also has the potential to reduce the risk of heart disease and stroke.
Dr. Ada Tang is working to understand how aerobic exercise can influence stroke risk factors and heart and arterial function in those who have already had a stroke. She will be evaluating the effects of an exercise program on 51 participants between the ages of 50 and 80, all of whom are one-year post stroke and can walk short distances without help. Participants will be randomly assigned to either an aerobic exercise program, or to a balance and flexibility program. Both programs are conducted at Vancouver General Hospital and feature three one-hour sessions per week. Program participants are carefully monitored during their exercise sessions. The participants’ fitness level and blood pressure will be tested at the start and the end of the six-month exercise program and two months after the end of the program to see if the benefits are maintained. Echocardiograms will be performed to look at heart size and function, blood tests will measure cholesterol levels and other signs of inflammation, and other tests will be done to determine how exercise can improve artery flexibility, heart rate and rhythm.
This study will help us better understand how exercise after stroke can improve heart function and heart health. Research results will help health professionals understand the best way to promote a healthy lifestyle after stroke to lower the risk of heart disease or another stroke.
Each human cell contains instructions — in the form of genetic material or the genome — to direct its growth, function and death. The genome is made up of three billion molecules called nucleotide pairs, which are joined in a specific sequence. Sometimes the nucleotide sequence in a cell’s genome can become altered, or mutated, and these mutations can lead to changes in the cell that cause cancer. The spread of cancer cells from the primary tumor is known as metastasis. Relatively little is known about the mutations in the genome that create, control and direct metastasis. Next-generation sequencing allows researchers to rapidly “read” the sequence of the three billion nucleotide pairs in the genome of cancer cells. Using this technology, Dr. Jill Mwenifumbo aims to identify the sequence mutations that are unique to, and perhaps essential for, colorectal cancer metastasis. Ultimately, discovering the genetic mutations that drive metastasis will help identify potential drug targets, which will lead to more effective treatments for this disease. Given that colorectal cancer is the second leading cause of cancer death in Canada, effective treatment has enormous potential to improve personal and population health.
