Prostate Cancer is the most common cause of cancer and the second leading cause of cancer death in men in North America. But removing the androgens (male sex hormones) that regulate tumour growth — the only existing therapy shown to prolong survival — only produces temporary remission. Surviving tumour cells usually recur, becoming androgen independent. To improve survival, new therapeutic strategies must be developed. Dr. Alan So is exploring a novel way to treat prostate cancer at the molecular level. He is observing how prostate cancer is affected by shutting down two common genes in prostate cancer cells: IGFBP-2 and IGFBP-5 (insulin-like growth factor binding proteins). These genes are essential for prostate cancer to grow and spread to the bones. His research is also examining the effect of combining this treatment with chemotherapy on prostate cancer cells. The ultimate goal is to develop a more effective treatment for prostate cancer that can be tested in clinical trials.
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The contribution of amyloid-induced neuroinflammatory factors to disturbances in neural processes related to learning and memory
Close to 250,000 Canadians over the age of 65 have Alzheimer’s disease. The leading cause of dementia, Alzheimer’s is a degenerative disease characterized by loss of memory, judgement and reasoning, and changes in mood and behaviour. There is no known cause or cure. Within the brain, cells shrink or disappear and are replaced by dense spots, or plaques, which contain a protein called beta amyloid. Recent studies show chronic inflammation in the brain cells plays an important role in the development of Alzheimer Disease. Microglia — the smallest cells surrounding neurons — seem to contribute to this process, and the beta amyloid protein interacts with these cells. Dr. Aline Stephan is studying how amyloid deposits inside the brain induce neural changes to affect synaptic processes and memory function. Her research will help explain how inflammation exacerbates memory deficits, and may lead to new therapies to treat the disease.
Investigating protein expression and localization in microsporidian parasites during infection
Dr. Ross Waller’s earlier research into the malaria parasite has contributed important information leading to a new array of drugs to treat the disease. Now he is studying microsporidia, a group of intracellular parasites that infect humans and animals. In particular, microsporidia infect immune-compromised individuals, causing encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach and intestines). The parasites have a remarkable method for invading host cells. This small, simple spore releases a harpoon-like tube that pierces the host cell. The parasite contents are then injected into the host through this tube, establishing the infection. Ross is identifying specific genes and proteins involved in the infection process, using genome sequences that have identified all the genes in two microsporidia. He is looking at the way proteins are prepared prior to and during the initial stages of infection. The results may provide new ways to combat these organisms.
A postdoctoral program to enhance planning and quality improvement initiatives in mental health through the validation of administrative mental disorder diagnoses
While a number of significant improvements in treatment of mental disorders have been made in recent years, gaps remain. For example, major depression is identified in only 50 per cent of people with the disorder when they visit their family doctor, and only half of those people receive appropriate treatment. Initiatives to address these gaps include programs that provide public and physician education and increase connections between care providers. However, it’s unclear how successful these initiatives will be due to a lack of data on the prevalence of mental disorders and whether people improve as a result of these programs. Dr. Paul Waraich is evaluating whether data routinely collected from hospital and physician visits, as well as medication prescriptions, are of sufficient quality to be used to evaluate changes in the care of major depression and other mental disorders. The research could greatly improve understanding of whether new mental health care programs are effective.
Analysis of specific host responses to pathogenic Escherichia coli infection
Escherichia coli (E. coli) bacteria cause much disease and death worldwide. However, little is known about the mechanisms these bacteria and others use to cause disease in their hosts. Specific virulence factors – strategies and molecules that enable the bacteria to cause infection – are needed for disease to develop. The bacteria inject these virulence factors into host cells, which affect normal cellular processes. Dr. Mark Wickham is using two pathogens, E. coli and Citrobacter rodentium, as a model to research how pathogens produce disease at the molecular and cellular levels. Understanding how this process occurs will address a gap in current knowledge, thus improving health and health services, and the research results could be applicable to other disease-causing organisms.
Baseline HIV RNA and mortality after the initiaton of HARRT: Exploring the mechanism that explains the association
Before triple-drug antiretroviral therapy was developed to treat HIV, certain levels of HIV ribonucleic acid (RNA) in the blood were strongly associated with progression of the disease. However, there has been a great deal of uncertainty about the clinical relevance of HIV RNA levels since the therapy was introduced. Recent studies have produced conflicting results about the association of HIV RNA levels with survival or death for individuals with HIV. But these studies did not assess patient adherence to triple-therapy treatment. Dr. Evan Wood is using data from the BC Centre for Excellence in HIV/AIDS Drug Treatment Program to research the association between HIV RNA levels and survival after beginning triple-drug antiretroviral therapy. He is also investigating the relationship between HIV RNA levels and factors such as non-compliance with triple therapy treatment. The findings could be used to adapt provincial guidelines for HIV/AIDS treatment.
Muscle metaboreflex during exercise in chronic obstructive pulmonary disease
Chronic Obstructive Pulmonary Disease is a progressive lung disease that causes breathing difficulties and chronic cough. Those affected often have weak arm and leg muscles that are easily fatigued, which can cause them to avoid exercise and adopt an inactive lifestyle. Dr. A. William Sheel’s research is directed at understanding how reduction in blood flow and oxygen during exercise leads to muscle fatigue and how different types of exercise affect the amount of fatigue. Results from his study will help explain why people with chronic lung disease become prematurely fatigued and could be used to design exercise rehabilitation programs to improve their health.
Obesity in the community: a comparison of the differential distribution of body fat in four distinct populations
Being overweight or obese, especially around the stomach, dramatically increases one’s risk for health problems such as diabetes and heart disease. This is of great concern as the prevalence of obesity in Canada has steadily increased during the past 15 years. However, most of the research on obesity is based on populations with European origins; very little is known about the effects of being overweight in Aboriginal, Chinese and South Asian populations yet the rates of obesity in these populations are also increasing. Preliminary evidence suggests that at the same weight and stomach size, people of Aboriginal, Chinese or South Asian descent have a higher amount of body fat and greater risk for diabetes and heart disease compared to men and women of European descent. Therefore, using clinical targets for obesity developed from European populations may result in inappropriate screening for prevention of these diseases. Dr. Scott Lear’s research involves recruiting 200 people from each of the Aboriginal, Chinese, South Asian and European communities to study the relationship between cultural background, body fat distribution and risk for diabetes and heart disease. Each participant will undergo a scan for stomach fat, overall body fat and risk factors. By improving understanding about the implications of excess body fat in these under-studied populations, the research could lead to guidelines for identifying people at risk for chronic disease, and contribute to prevention strategies targeted to these populations.
Modeling musculoskeletal diseases: from epidemiology to quality of life
Osteoarthritis (OA), which results in the breakdown of joint cartilage, is the most common form of arthritis. Despite much research on the condition, there is no primary prevention strategy for the disease. Macro-level studies evaluating different prevention and treatment strategies are also needed. In collaboration with colleagues in Canada, the US and Europe, Dr. Jacek Kopec is conducting three osteoarthritis studies. The first involves the development of a computer simulation model of OA. The model will synthesize data from different sources, creating the world’s largest database simulating the nature history of OA. Results from this study will be used to assess prevention strategies and develop optimal treatments for the disease. The second study investigates whether or not moderate physical activity can cause OA. The third study focuses on patients’ preferences about different treatment options for OA of the hip and knee. As part of the study Dr. Kopec is developing a questionnaire that can be adapted to individual respondents, making the assessment more precise and efficient than previous questionnaires. The studies as a whole could advance knowledge of osteoarthritis and improve treatment of the condition.
Dendritic cells in autoimmunity and cancer
Dendritic cells play a vital role in regulating the immune response. They are the only cells capable of activating T cells that have not previously been exposed to a particular antigen (immune threat) to recognize and mount an attack on these foreign proteins. This process ensures an appropriate immune response against potentially harmful antigens. Dendritic cells are also thought to have the ability to instruct the immune system to ignore certain antigens, establishing a state of immune tolerance in the body. When the balance between immune activation and immune tolerance is disrupted, the result may be the development of autoimmune disorders in which the immune system attacks body tissue or cancer in which tumour cell growth goes unchecked. Dr. Cheryl Helgason is studying the biology of dendritic cells and the mechanisms by which they interact with T cells to activate an immune response or to establish immune tolerance. Such research could suggest ways of manipulating immune function to develop new methods of treating cancers, autoimmunity and other diseases involving immune dysfunction.