Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide and affects ~1% of Canadians. Its chronic inflammation causes pain and joint failure, eventually leading to disfiguration and disability. The cartilage and bone destruction of RA is thought to be caused by a certain family of enzymes, MMPs, that are capable of breaking down all joint components, causing severe damage and pain. Recently, 14-3-3 proteins were discovered to be critical communication proteins between skin cells during the healing process. 14-3-3 proteins also stimulate production of MMPs. Thus, the abnormally high amounts of 14-3-3 found in RA joints might be responsible for excess MMPs production, which leads to joint destruction. Jennifer is studying how 14-3-3 proteins may stimulate production of MMPs and lead to the joint destruction in RA. Ultimately, her work will contribute to the development of novel therapeutic strategies to diagnose and treat RA and other arthritic diseases.
Research Location: Vancouver General Hospital
Physical Activity, Local Joint Factors and Osteoarthritis
Osteoarthritis is a leading cause of disability in Canada. This type of arthritis causes deterioration in the joints, leading to swelling, pain and stiffness. It often results in lost work time and places limits on an individual’s normal function and recreational activity. Both the increasing prevalence of osteoarthritis in the province’s aging population, and the lengthy surgical wait times for replacing osteoarthritic joints are high profile health care issues in British Columbia. Physical activity can offer almost universal improvements in health, which includes decreasing the risk of heart disease, stroke, high blood pressure and cancer. Health Canada recommends all adults participate in at least 30 minutes of moderate-intensity exercise most days. But some types or too much physical activity, such as competitive sports or heavy physical work, can cause excessive wear and tear in the joints, increasing the risk of osteoarthritis. In addition, some people may be more vulnerable to the type or amount of physical activity because of the way their legs are aligned (e.g. bow-legged) and/or because of increased flexibility (hypermobility). Chuck Ratzlaff is comparing data on lifetime physical activity and these joint factors in people with knee and hip osteoarthritis to those who don’t have the condition, as part of a national arthritis study. The results can be used to recommend appropriate amounts and types of physical activities that may decrease the risk of osteoarthritis of the hip and knee.
Melanoma gene therapy by conditional replicative adenovirus targeting PUMA and p-Akt
Melanoma is a deadly form of skin cancer arising from the abnormal growth of pigment-producing cells in the skin. Melanoma is an aggressive tumour that spreads quickly to other parts of the body and is very difficult to treat because it does not respond to radiation or chemotherapy. In recent years, researchers have turned to gene therapy as a new approach to fight cancer. This approach is based on the idea that cancer is caused by defective genes. The goal is to eliminate the cancer by inserting therapeutic genes into cancer cells using a vector (a vehicle for delivering genetic material to a cell). Within melanoma cells, the expression (activation) of the cell death gene PUMA is often reduced and expression of the cell growth and survival gene Akt3 is often inappropriately increased. Using viral vectors known as CRAds, Alison Karst is focusing on reversing this pattern of gene expression in order to induce melanoma cell death. CRAD-based gene therapy holds promise for eliminating cancer cells and more effectively treating melanoma.
Economic studies in BC seniors at high risk of injurious falls
Falling and fall-related injuries are a major health concern for the elderly. It is estimated that 40 per cent of people over age 75 will experience a fall at least once per year. This is a health issue with significant costs to the healthcare system, and to the elderly population. Fall prevention programs exist; however, research and evidence on the cost-effectiveness of these programs is lacking in Canada. The analysis of the costs and cost effectiveness of health technologies is becoming an increasingly important issue in healthcare decision-making. If economic evaluations are missing, decision-makers will lack an important aspect for fully informed decision-making. John Woolcott is conducting one of the first Canadian-based costing assessments of the impact of falls and is investigating the cost effectiveness of fall prevention programs. John is determining the direct and indirect costs of injurious falls in BC and evaluating the cost-effectiveness of existing interventions currently in place to reduce seniors’ falls. He is also focusing his research on how injurious falls affect the quality of life of 400 seniors in BC. John’s research will further educate the health care community regarding the substantial costs of falls and will further inform decision-makers regarding cost-effective interventions.
Cognitive and behavioural characterization of individuals genetically at risk for frontotemporal dementia
Frontotemporal dementia (FTD) is the second most common form of dementia affecting individuals under the age of 65. Characterized by the gradual wasting away of the brain’s frontal and anterior temporal lobes, FTD progressively affects mental function, personality and behaviour, while leaving memory largely intact. Over time, they lose the ability to organize and plan, become emotionally blunted and socially inappropriate, lose insight on the impact of their behaviour, and experience difficulty with speech and language. Currently, there is no cure for FTD and treatment methods are limited. Vulnerability to some forms of FTD has been linked to a specific gene mutation that runs in families. While the symptoms of FTD are well documented, few studies have looked at the characteristics of individuals who carry the mutation but do not yet show obvious FTD symptoms. However, research shows that even when they do not exhibit obvious symptoms of FTD, individuals who carry the gene mutation perform significantly worse on tests that measure frontal lobe functioning than family members who do not carry the mutated gene. Using measures such as cognitive testing, behavioural questionnaires and brain imaging, Amanda LaMarre is seeking to establish clinical markers of FTD in genetically at risk individuals in order to identify and distinguish the earliest symptoms. She hopes that by gaining a better understanding of the development and onset of FTD, her research will provide a base for future research aimed at preventing or slowing the progression of the disease.
Dying for choices: decision-making in end-of-life care
Every year more than 185,000 Canadians die in acute-care settings. Previous research has shown that patient choices regarding care are extensively influenced by factors inherent in the place of death. However, no Canadian research has examined how end-of-life care (EOLC) decisions are influenced and shaped through these factors. The focus of Marian Krawczyk’s research is to examine EOLC decision-making within acute-care settings, specifically in regards to the use of life-extending technologies. Her study examines factors that are overlooked in existing research including the location of communication when discussing EOLC options, differing medical models of palliative care, doctor-patient communication, and the social capital and economic resources of patients. By providing data that examines communication in EOLC in British Columbia, this research seeks to strengthen the ability of health care providers, patients and families to effectively communicate and negotiate patient care choices before and during acute care settings. The research will also increase the ability and efficiency of policy makers in the delivery and distribution of health services. Finally, it may help improve communication and decrease consumer-driven health costs.
Cardiovascular morbidity and mortality associated with the use of corticosteroids in patients with rheumatoid arthritis: a population based study
More than 300,000 Canadians have rheumatoid arthritis (RA), a disease that causes chronic pain and inflammation in the joints. In British Columbia, more than half of people with rheumatoid arthritis receive corticosteroids to reduce inflammation. Several studies have shown that patients with RA are more likely to develop and die from cardiovascular disease (CVD) and, on average, live 12 years less than people without RA. The increased risk for CVD cannot be fully explained by traditional risk factors such as smoking, high blood pressure, diabetes, high cholesterol and a family history of CVD. Disease severity as well as treatment used in the management of the disease seems to play an important role in the development of CVD. Dr. Antonio Aviña-Zubieta is studying cases of individuals in BC who were diagnosed with RA between 1997 and 2000, and evaluating outcomes in people who received corticosteroids with those who did not to determine if there are differences between the two groups in the number of heart attacks, heart failure and stroke. This will help to establish if corticosteroids used in the treatment of rheumatoid arthritis contribute to CVD. He also will study whether the brand, dose and duration of use with different drugs influence the risk of heart disease. The results could offer new insights, leading to improved treatment and management of rheumatoid arthritis and other conditions for which these drugs are commonly prescribed.
Identification of Mycobacterium tuberculosis virulence factors by pathogen effector protein screening in yeast (PEPSY)
Tuberculosis is a devastating disease that infects one-third of the world’s population, leading to eight million new cases and three million deaths per year. The prevalence of this disease is largely due to the ability of Mycobacterium tuberculosis (the bacteria that causes tuberculosis) to evade destruction by the immune system. Normally, when bacteria invade the body, the human response system triggers specialized cells called macrophages to engulf and destroy bacteria. In the case of tuberculosis, M. tuberculosis succeeds not only in escaping annihilation, but is able to enter and live inside the very cells that are programmed to destroy it. Using yeast as a model organism, Emily Thi is studying and identifying the components of the arsenal that Mycobacterium tuberculosis uses to successfully infect and survive within human macrophages. Her research on M. tuberculosis proteins that disrupt normal macrophage function may lead to the identification of novel targets for drug and vaccine development, which could result in new strategies to combat this challenging disease.
Mechanistic approaches to androgen-independent prostate cancer
Prostate cancer is the main form of cancer affecting men in the western world. Because cellular mutations within the prostate are regulated in part by androgens (male sex hormones), treatment of prostate cancer usually involves starving the prostate of androgens. While this therapy initially stops cancer progression, over time, the cancer continues to progress. Jennifer Locke is researching why prostate cancer progresses despite the apparent lack of androgens during treatment for the disease. Jennifer is testing the hypothesis that new androgens are produced within the prostate during androgen-deprivation therapy, causing the cancer to reoccur. Using molecular and analytical techniques, she is investigating androgen synthesis pathways. This research could enable identification and evaluation of inhibitors of these pathways, which may lead to new therapeutic options. Her ultimate goal is to improve treatment outcomes and quality of life for prostate cancer patients.
Death anxiety and spousal caregiving of persons with dementia
Persons with a dementing illness such as Alzheimer disease are often cared for at home by family members. Caring for someone with Alzheimer disease can be a stressful and challenging experience. Death anxiety (the fear of death or the dying process) is one issue that has received little attention in research on family caregivers of persons with dementia. As a person with Alzheimer disease may die within years of receiving this diagnosis, a family member may experience death anxiety through fear of watching the person they care for die, or fear of dying while the person with dementia still needs their support. Anthony Kupferschmidt is seeking to understand the degree to which family caregivers of persons with dementia experience feelings of death anxiety and the effect of these fears on their health and ability to cope and continue in their caregiving role. Findings from this research could ultimately contribute to improvements in education and other community-level programs to better support caregivers of persons with a terminal diagnosis. Anthony is also the 2006 recipient of the Canadian Association on Gerentology Margery Boyce Bursary. This award supports post-baccalaureate students who have made a significant contribution to their community through volunteer activities with or on behalf of seniors and who are registered in a program of study focused on aging or the aged. This prestigious award is the only national award available to gerontology graduate students that is not granted on the basis of financial need.