Dr. Boyle’s research will investigate the role that physical activity and sedentary behaviour play in the development of non-Hodgkin lymphoma, multiple myeloma, and breast cancer.
This project aims to: 1) examine the associations between physical activity and sedentary behaviour and the risks of non-Hodgkin lymphoma and multiple myeloma, and 2) investigate whether the effects of physical activity and sedentary behaviour on the risks of non-Hodgkin lymphoma and breast cancer are modified by particular genes.
These research questions will be investigated using data from four case-control studies (three of which were conducted in British Columbia), as well as pooled data from an international consortium of case-control studies.
This research will provide new and important information about the associations between physical activity, sedentary behaviour, and cancer. Identification of modifiable risk factors is particularly important for the prevention and control of these cancers, as little is known about their etiology.
Significant proportions of stroke survivors suffer long-term physical disability and are predisposed to sedentary lifestyles. This limits their performance of activities necessary for independent living in the community and contributes to increased risk for recurrent stroke and heart disease. Dr. John Best recognizes that intervention strategies are needed to motivate stroke survivors to engage in routine physical activity and to optimize their physical and motor functions.
Best’s research will examine executive functions (EFs) as mediators of a mental and social enrichment intervention for older adults with chronic stroke. Broadly speaking, EFs refer to the cognitive processes that allow for adaptive behavior and self-control.
One promising strategy targets EFs by engaging stroke survivors in complex mental and social activities. Best’s research will evaluate the importance of improving EFs within the context of a mental and social enrichment intervention in order to have a meaningful impact on physical and motor functions, the ability to perform daily activities, and routine engagement in physical activity.
The information garnered from Best’s research will be crucial for improving stroke rehabilitation for older Canadians who suffer chronic disability from stroke.
Gram-negative bacteria such as E.coli, salmonella, shigella, pseudomonas aeruginosa, and yersina pestis are responsible for a wide range of diseases. A common trait shared by these bacteria is their capacity to inject toxins directly into the cells of infected individuals using a syringe-shaped “nano-machine” called the Type 3 Secretion System injectisome. Preventing the injectisome from performing its function would effectively prevent these bacteria from causing a disease.
The injectisome is an important target for the development of novel treatments against bacterial infection. This research project will attempt to obtain a “map” of the injectisome at the level of individual atoms. Such a map will allow us to understand how different components interact to assemble such a “nano-machine” at the surface of the bacteria, and the mechanism by which the injectisome can inject toxins into human cells.
To map the injectisome at the level of individual atoms, Dr. Bergeron will use a range of biophysical methods, such as X-ray crystallography, nuclear magnetic resonance, electron microscopy, and molecular modelling.
A map of the injectisome could be used to design novel antibiotics or vaccines, which would function against a wide range of bacteria. In addition, understanding the mechanism of this nano-machine could allow the development of microscopic targeted injection devices with a wide range of potential applications.
Half of individuals recovering from a stroke have some form of impaired cognition, which hampers their independence. One possible contributor to impaired cognition after stroke is the presence of small “silent” lesions, which are detected in up to 28 percent of individuals with stroke.
Currently, there is little data describing the impact of silent lesions on stroke recovery. This study will determine if impaired cognition after stroke is associated with the presence and quantity of silent lesions.
Multimodal neuroimaging will identify how silent lesions affect brain function after stroke and determine if the number and/or type of silent lesion differently impacts cognition or brain function. The impact of silent lesions on brain function will be assessed by measuring cerebral vascular reactivity and examining neural network activity during a cognitive task.
Together with a battery of cognitive assessments, these measures will help explain how silent lesions alter cognition after a stroke. This knowledge will lead to the development of new interventions that account for silent lesions, resulting in improved quality of life for Canadians with stroke.
Anthracyclines are a class of drugs used world-wide for the treatment of most cancers. However, their clinical utility is limited by a high risk of cardiac toxicity and congestive heart failure.
Dr. Aminkeng aims to identify genetic markers that can predict anthracycline-induced cardiotoxicity and congestive heart failure using a genome-wide association study (GWAS). The goal is to develop a clinical test that will allow for better identification of risk factors and improved treatment and monitoring that will increase the safety of anthracycline therapy.
Study participants have been recruited via the Canadian Pharmacogenomics Network for Drug Safety. Patients will be genotyped using the GWAS Illumina Infinium assay. In vitro, in vivo, and pharmacokinetic studies and pharmacodynamics modelling will be used to study the functional relevance of identified genes.
A highly predictive test for anthracycline-induced cardiotoxicity and congestive heart failure would significantly benefit patients, families and physicians by improving counselling and treatment options. For example, a patient at high risk could receive more aggressive echocardiogram monitoring for toxicity, receive a cardio-protective drug such as dexrasoxane, or be treated with an alternative chemotherapy protocol.
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.
