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 womenâs 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 womenâs 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.
Year: 2006
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 recipientâs 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
âHighly active antiretroviral therapyâ (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 Canadaâs 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 Crohnâs 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 bodyâs response to early infection, and recent research suggests that dysfunction of this innate response may contribute to Crohnâs 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 firefightersâ 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 Kirkhamâs 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 firefightersâ 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 â 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.
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 Krawczykâs 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.
Aging and the Brain: Is reduced function of medial-frontal cortex responsible for motor control deficits in the elderly?
Motor control deteriorates with age. For example, people over the age of 65 commit more traffic errors than younger drivers. However, it remains unclear the extent to which this increased error rate is brought about by failures of high-level cognitive control systems within the medial-frontal region of the brain as opposed to other body/brain systems. Olave Krigolson is assessing the degree to which errors by elderly individuals performing continuous motor tasks result from an impairment of error processing systems within the medial-frontal cortex. He is observing brain activity in this region of cortex during a series of experiments that will test continuous tracking and decision-making abilitiesâtwo types of tasks that are important for driving. Olaveâs research will improve our understanding of why motor errors occur more frequently among older people. Furthermore, it may help develop novel techniques for assessing the functionality of motor control systems in the elderly.
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 brainâs 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.