Continuing the study that he began in his MSFHR-funded Master’s work, Malachi Griffith is examining the changes in the forms of certain genes due to alternative splicing that may be important in the progression of cancer. Alternative splicing is a phenomenon in which one gene is assembled from its component pieces in many different ways, a process which produces immense diversity and enables genes to fulfill many functions. This diversity in gene structure may also account for the differences in the severity of cancers and response to treatment observed among individuals. Malachi is studying colon and prostate cancer cells – some that are responsive to treatment, and others that are resistant. By studying differences in the structure of expressed genes between these contrasting states, he hopes to gain insight into why treatment initially appears to work well in some patients, yet becomes less effective over time. Such knowledge may lead to improved or novel treatment strategies, resulting in better outcomes for cancer patients.
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British Columbia Transient Ischemic Attack Project
A transient ischemic attack (TIA) occurs when there is a temporary disruption of blood supply to the brain. Damage from a TIA is temporary and reversible, but the experience is an important warning symptom for stroke, which is a major cause of death and long-term disability. Patients have a five to ten per cent risk of having a stroke within a week of a transient ischemic attack. Patients with TIA symptoms often go to the emergency department for evaluation, but there is no universally accepted strategy for managing TIA in B.C. Emergency Departments (EDs). A major challenge has been the lack of a system for determining which patients are at high risk for having a stroke and warrant urgent investigation and treatment. Dr. Devin Harris is evaluating the effectiveness of a clinical guideline for standardizing TIA care in EDs. This evidence-based guideline is being implemented as a pilot project in six B.C. emergency departments and will then be expanded to all 92 EDs in the province. Devin is examining physician adherence to the guideline and the impact on patient outcomes. This information will be used to develop a model for predicting which patients are at high risk of stroke after TIA, leading to better preventive and treatment options.
Preventing Vicarious Traumatization of Mental Health Therapists: Identifying Protective Practices
As part of their work, trauma therapists must listen to detailed descriptions by patients of horrific events such as abuse, violence and disasters. Over time, the psychiatrists, psychologists, social workers and psychiatric nurses who treat seriously traumatized individuals are themselves at risk for vicarious traumatization and burnout. Richard Harrison is studying the factors that contribute to the resilience and health of trauma therapists. He will identify the individual characteristics, as well as the organizational practices, that help professionals succeed in their work and remain healthy. He hopes his work will help lessen the “costs of caring” for this group of health professionals, and prevent the loss of therapists who quit the profession because of burnout and vicarious traumatization.
Decision Making Related to Cancer Risk-Reduction Among BRCA1/2 Carriers
Women who learn through genetic testing that they are at high risk for developing hereditary breast and ovarian cancer may choose to undertake several risk-reducing strategies, including surgery, chemoprevention, and increased screening. An emerging body of research is beginning to describe high-risk women’s experiences and satisfaction upon adopting these risk-reducing strategies; however, little is known about how women come to make these decisions. Because of the highly personal nature of this decision, most health care providers attempt to support decision-making about risk-reducing strategies, rather than recommend particular courses of action. In order to support women and to develop and evaluate appropriate interventions, it is essential to understand how women arrive at these decisions. Fuchsia Howard is identifying the personal, psychological and social contextual factors that influence women’s decision-making about breast and ovarian cancer risk-reducing strategies. This research will contribute to an understanding of the impact of genetic testing for hereditary breast and ovarian cancer risk on the psychological health and quality of life of women found to be at high-risk. This understanding will inform future development of appropriate interventions within programs offering genetic services.
Cytochrome p450 2C Inhibition in Peri-transplant Ischemic Injury and Transplant Vascular Disease
Transplant vascular disease (TVD), characterized by a thickening of the arteries (arteriosclerosis), is the primary cause of chronic heart transplant rejection. TVD can be detected in up to 75 per cent of transplant recipients within only one year of transplantation. One factor that causes TVD is oxidative stress which occurs during the process of transplantation when blood flow is stopped in the donor heart prior to transplantation (ischemia), and then re-established in the recipient (reperfusion). This stress not only damages the heart but also makes it more susceptible to attack by the recipient’s immune system leading to chronic rejection. Previous research has suggested that an enzyme (CYP2C) is involved in triggering oxidative stress and heart damage during reperfusion. Arwen Hunter is investigating the process and mechanisms by which CYP2C causes cardiovascular damage. She will also investigate whether inhibition of CYP2C can suppress the amount of damage that occurs during transplantation and whether suppression of this damage can reduce chronic rejection later on. Results from these studies may lead to novel therapeutic strategies to alleviate chronic heart transplant rejection.
Socio-ecological analysis of HIV/AIDS treatment-related behaviours and health outcomes in an era of HAART: Considering individuals in the context of their communities
“Highly active antiretroviral therapy” (HAART) has led to dramatic improvements in quality of life and survival for people infected with HIV/AIDS. But these positive outcomes are not evenly distributed among HIV-infected individuals. Despite access to free medications in Canada’s publicly funded health care system, vulnerable groups such as HIV-positive women, injection drug users and socio-economically disadvantaged people have not experienced the health improvements others have. Research to date has focused largely on individual risk factors. Angela Kaida is examining how individual and community factors, such as neighbourhood income levels and the availability of HIV/AIDS services, affects the quality of treatment and health outcomes of people infected with HIV. Angela is assessing the role these factors play in delaying entry into treatment, non-adherence to treatment, and the advance of HIV/AIDS disease and death. In earlier research, Angela studied the impact of HIV/AIDS on agricultural production, food security and rural livelihoods in Malawi, and on male involvement in family planning in Uganda. The findings from her current study have the potential for application in the design of community programs and policies to improve equal access to HAART in Canada, and may be applied in global settings with high HIV prevalence.
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.
Regulation of innate epithelial response against A/E bacterial pathogens by TLR5 and single Ig IL-1R-related (SIGIRR) molecule
Bacterial infections in the intestine cause diarrheal disease worldwide, affecting people of all ages. These bacteria also trigger inflammatory conditions of the digestive tract such as in Crohn’s disease and ulcerative colitis which can lead to chronic illness and hospitalization. Growing evidence suggests that the innate immune system is critical in regulating the body’s response to early infection, and recent research suggests that dysfunction of this innate response may contribute to Crohn’s disease. A strain of Escherichia coli (E. coli) that attaches to cells on the inner lining of the intestine is a major cause of diarrhea in children, but little is known about the mechanisms by which the immune system recognizes and responds to this type of bacterial infection. Mohammed Khan is investigating how the innate immune system detects E. coli infection and the mechanisms that regulate subsequent inflammatory events in the intestine. Using laboratory-grown human intestinal cells and mouse models, Mohammed hopes to reveal novel mechanisms of regulation of inflammation in host defense. This research may lead to new treatments for infectious and inflammatory diseases of the human intestine.
Assessing risk of myocardial infarction among fire fighters
Firefighters work in hazardous environments that may put them at risk of developing diseases such as cardiovascular disease. While job-related exposure to hazardous conditions is believed to increase firefighters’ risk of heart attack, there is little data available regarding their levels of exposure to hazardous work conditions and the risk associated with health outcomes. Canadian policy-makers are seeking new evidence to help them develop compensation programs and policies with regards to the risk of cardiovascular disease associated with work-related exposures among firefighters. Tracy Kirkham’s research is directed at identifying the types of hazardous exposures that may be related to an increased risk of heart attack among firefighters. Her study includes firefighters who had a heart attack while working at one of seven BC fire departments between 1984 and 2000. She is also monitoring and analyzing firefighters’ exposure to air pollutants and noise as well as using other indicators of exposure, such as signs of physiological stress, and numbers and types of fires fought. The results of this study may provide policy-makers with information to help inform decisions regarding compensation for work-related heart disease among firefighters. In addition, the results may be applied to other occupational groups with similar exposures to hazardous substances.
Neuroprotective mechanism of connexin43
Stroke is one of the leading causes of death in North America affecting about 16,000 Canadians each year. This disease causes a sudden loss of blood to an area of the brain typically due to blocked or ruptured blood vessels. Michael Kozoriz is studying how to reduce brain damage caused by stroke. The brain has two classes of cells – nerve cells (neurons) and glial cells. Neurons conduct electrical impulses, while glia surround, support and protect neurons. Glia are the most abundant cells in the central nervous system and are connected by a junction made of a protein called connexin43. Because these cells are physically attached they have the ability to share various molecules and nutrients. Studies have shown that stroke damage is less severe in the presence of connexin43, and damage is greater if the protein is absent. Michael is examining how connexin43 protects cells from death. He suspects the junctions remain open during a stroke, allowing neighbouring cells to share nutrients, much like neighbours helping a friend in need. His findings could explain how to protect the brain during stroke, and ultimately, lead to better treatments for this disease.