Smoking is the major cause of preventable death in Canada, accounting for more than 45,000 premature deaths per year and 30 per cent of all cancer deaths. Most smokers begin to smoke as teenagers, and tobacco advertising and promotion are among the main motivators for tobacco use, especially in youth. Currently, tobacco companies are spending the majority of their marketing dollars in retail stores, compared to any other advertising venue. Since most teenagers shop at convenience stores at least once a week, adolescents are routinely exposed to tobacco advertising. Little research has examined the extent and impact of these “Point of Purchase” (POP) activities in Canada. Helen Hsu is studying the links between smoking prevalence among youth and environmental influences, including POP advertising, pricing, signage and retail locations. She is using Geographic Information System technology to gather and analyze social-demographic, economic and geographic information. Her work could help explain the impact of tobacco industry activities on adolescent tobacco use across Canada, and provide insight into the effectiveness of tobacco control strategies in schools and communities. This information will be useful for setting public health policies and developing tobacco control programs.
Role of the Rap GTPases and the Pyk2 tyrosine kinase in B cell adhesion and spreading
B lymphocytes (B cells), which develop from stem cells in the bone marrow, are specialized immune cells that produce antibodies to fight infections. After developing they move into the blood stream where their role is to detect pathogens and be activated by the encounter to mount an immune response against infectious microbes. An important cellular process called adhesion is involved with the development and activation of B cells. Adhesion is the process whereby receptors on the surface of the B cells bind to receptors on the surface of other cell types. A protein called Rap acts as a molecular switch that cycles between an “on” or “off” state to regulate cell adhesion. Kevin Lin is studying the mechanisms of how Rap regulates B cell adhesion and cytoskeleton remodeling. In particular, he is investigating Rap’s control of the activation and function of Pyk2 (nonreceptor protein tyrosine kinase), believed to be involved in regulating the form and structure of the cell in response to antigen binding and chemokine signaling. This work will provide new insights into processes that regulate the development and activation of B cells, and may be important for a better understanding of inflammatory responses, autoimmune diseases, cancer of B cells, and other immune related diseases.
Exploring a community approach to enhance the healthy development of youth
Youth across BC are exposed to a variety of risk factors that can inhibit their ability to develop into healthy adults. Some of these risks include alcohol and drug use, gambling, physical and sexual abuse, harassment and discrimination, obesity, and feeling unsafe at school. Most funding agencies support one-time projects to improve health and social outcomes among youth. Although these interventions are intended to target needs identified by the community, many are unable to generate long-term change toward healthy youth development, because of short-term grants, competing goals, a lack of trust in the community and uneven volunteer support. Carol Sparks is studying how an alternative approach—community action projects—creates sustainable change. Community action shifts the focus from one-off projects to a community-centred approach, based on the belief that families provide the primary support for children and youth, and vulnerable youth need community support to meet their health and social needs. Carol is working in collaboration with the communities of Courtenay and Campbell River on Vancouver Island to determine the processes used by local community action projects to address the social and economic determinants of youth health. This research will identify both barriers to sustainability and strategies that support sustainability.
T Regulatory cells in toxoplasma pathogenesis
Toxoplasma gondii, commonly acquired by eating under-cooked meat, is a particularly successful pathogen that establishes life-long infections with its capacity to infect, replicate and persist chronically within host immune cells. Toxoplasma causes an acute, influenza-like disease that typically becomes a chronic infection. Immuno-suppressed individuals are at risk for developing chorioretinitis (inflammation of the choroid layer behind the retina), blindness and fatal encephalitis. An emerging concept in the immunology of infectious diseases is that persistent pathogens like Toxoplasma establish chronic infections by activating T regulatory cells (Tregs), which are thought to have the ability to selectively suppress immune responses. Dr. Andrew Hall is investigating the immunological basis of Toxoplasma persistence and how this pathogen evolves to promote Tregs. He aims to determine the molecular details governing Treg generation and function, and to establish their role as critical immune regulators of persistent infections. Andrew hopes that results from his research will help to develop novel methods of immunotherapy or vaccines designed to target the regulatory T-cell network in disease and to contribute significantly toward the development of cures.
Novel strategies for genetic modification and expansion of hematopoietic stem cells
Throughout life, blood cell production is dependent on a rare cell found in the bone marrow called the hematopoietic stem cell. This cell has the unique ability to divide and make identical copies of itself and also to generate progeny cells that can expand and acquire the specialized properties of mature circulating blood cells. Stem cells underpin a wide range of transplantation-based therapies for cancer, leukemia and genetic disorders. The use of these cells for therapeutic purposes requires genetic manipulation of hematopoietic stem cells, which involves inserting gene products directly into the cell’s genome. This procedure can also negatively affect chromosomes flanking the insertion site, causing variations in normal gene expression and malignant growth. Dr. Eric Yung is addressing these issues by developing methods to introduce new genes into stem cells without inserting them directly into the host genome. His strategy is to adapt and modify the ability of certain viruses to insert genetic material into cells. These methods may provide safer and more robust ways to achieve high level expression of genes. They may also aid understanding of the function of specific genes (for example genes that cause cancer) and the development of new methods to expand stem cells and develop new therapies for genetic disorders.
The effect of load and velocity on muscle activation and cutaneous reflexes during rhythmic human arm cycling
Stroke is one of the leading causes of disability in older adults. After stroke there may be deficits to movement control which typically are expressed as either too much activity in a muscle (spasticity) or too little activity in a muscle (low tone). These impairments interfere with normal movements involved in daily physical activities such as walking or reaching. Present rehabilitation programs include treadmill training with body weight support, with the focus mainly on the leg muscles. The speed and amount of body weight support required to maximize the rehabilitative benefits of treadmill training is not fully understood. It has been shown that the movement of the arms during walking can influence the walking pattern. Research has also shown that rhythmic movement such as walking is to a large degree controlled by neural circuits in the spinal cord called central pattern generators (CPG). More recently, it has been suggested that benefits to leg motor function result from retraining the CPG for the arms as well as the legs. This suggests that recovery of arm muscle activity may be important for the recovery of a normal walking pattern, and of leg muscle function as well as arm function. Sandra Hundza is exploring the most effective levels of speed and load to be used in an arm training protocol. By using harmless electrical stimulation of a nerve in the hand, she is evaluating muscle activity and reflexes elicited during rhythmic arm cycling movement. Results from Sandra’s research will determine what speed and load will best stimulate the spinal circuitry, thereby offering the best training protocol for arm cycling therapy. Her results will also have application to speed and weight bearing support for treadmill training protocols in general and help to better understand how rhythmic movement of the limbs are controlled.
Engineering of islets to produce the anti-diabetic hormone GLP-1
More than 2 million Canadians and 135 million people worldwide have diabetes, a chronic medical condition characterized by a lack of insulin (Type 1), or insensitivity to insulin (Type 2), a blood sugar-lowering hormone. Type 1 diabetes can be treated by transplantation of islets, which contain the insulin-producing cells, to patients, but use of this therapy is limited by the huge volume of islets required to treat all Type 1 diabetes patients. As a result, most continue to rely on insulin injections to help control blood glucose levels. Glucagon-like peptide-1 (GLP-1) is produced in the intestine and has numerous anti-diabetic effects. Clinical trials are currently investigating GLP-1 as a treatment for Type 2 diabetes. Other recent studies show GLP-1 also enhances the growth of islet tissue. As a 2003 MSFHR Trainee, Rhonda Wideman investigated the effects of GLP-1 on the growth and survival of transplanted islets to determine if GLP-1 reduces the amount of islets needed to treat Type 1 diabetes in transplant recipients. Now in a PhD program, Rhonda is examining the therapeutic potential of engineering islets to produce GLP-1. She is investigating whether islets in which GLP-1 production has been induced will indeed survive and function better following transplantation. This would reduce the amount of islets necessary for a successful transplant and enhance post-transplant islet function. Ultimately, Rhonda hopes her studies will contribute to improved islet transplantation protocols, which are more effective and less reliant on limited supplies of donor islet tissue.
Investigating the molecular basis of collagen's finely tuned stability with single-molecule manipulation techniques
Collagen is the fundamental structural protein in our bodies, which means changes in its chemical composition can have profound, widespread effects on health. For example, connective tissue diseases, the leading cause of disability and absence from work in Canada, can be caused by a change affecting only one position out of 1000 in the DNA sequence that codes for collagen. As we age, collagens in our body tissues become chemically modified, leading to structural changes that result in weakening of bone structure and the deterioration of joints, arteries and the retina, a situation that is exacerbated by diabetes. The controlled production and degradation of collagen is important for normal embryo development; a breakdown in this controlled pathway is also associated with the spread of cancerous tumors in the body. All of these health-related problems are related to chemical changes in collagen, which lead to changes in its structural and elastic properties at the tissue level. Dr. Nancy Forde is studying the elastic properties and stability of single collagen molecules, to identify the relationship between chemical changes and changes in the structure and function of collagen. Her team is employing the world’s smallest tweezers, optical and magnetic tweezers, to grab, stretch and twist single collagen proteins. This special equipment is currently applied to protein study at only a handful of labs worldwide. Dr. Forde and her team are directing their efforts to better understand how changes in collagen at the molecular level affect the elastic and structural properties of tissues. This research could help explain how tissues deteriorate with age, as well as the impact of these changes on the development and severity of diseases such as cancer and diabetes.
Seniors Preventative Health Intervention Program
To assess whether a pharmacist in consultation with family physicians can improve medication management for older patients thus reducing hospital admissions, health services and costs due to inappropriate medication use.
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Disabilities Health Research Network
The Disabilities Health Research Network is an integrated, multidisciplinary, and BC-based network that fosters high quality research to better the lives of Canadians with disability. It promotes research that solves real problems for persons with disability, improves clinical practices of relevance to the health of persons with disability, and leads to improved policies of relevance to persons with disability.