Structure-function relationship in smooth muscle contraction

Hollow organs such as the intestines, bladder, uterus, blood vessels, and the airways that make up lungs are lined with smooth muscle cells. Normal functioning of these organs depends on the ability of these cells to contract and relax – processes that control the volume and shape of the organs and enable them to perform their various functions. When an individual has asthma, excessive contraction of the airway smooth muscle results in airway narrowing, compromising the individual’s ability to breathe. In asthmatics, airway smooth muscle has a tendency to generate more force and shorten more extensively than in individuals without asthma. This condition is further exacerbated by the fact that the muscle cells adapt to this shorter length, making it difficult for asthmatic airways to open after an attack has occurred. Leslie Chin is studying the role airway smooth muscle plays in the development of asthma. Generally, asthma research focuses on relaxing the smooth muscle cells which is typically accomplished by using an inhaler; however, it is also important to focus on preventing these muscle cells from adapting to shorter lengths. Leslie is investigating how this adaptation occurs in asthmatics and how this adaptation is prevented in healthy people. Understanding how both the mechanics of airway smooth muscle in asthma and the alterations are altered could lead to new treatments for the disease.

Investigation of the impact of HLA genetic diversity on HIV sequence evolution and clinical correlates of HIV disease

One of the major challenges facing HIV treatment and vaccine design is the virus’ capacity to mutate extremely rapidly in response to a changing environment. The course of HIV infection within a given individual is characterized by a constant, dynamic evolution of the virus. It is now appreciated that a wide range of host genetic factors influences the course of HIV infection and disease progression. The proposed research project seeks to investigate the effects of genetic variation within specific genes of the human immune system (called the “”Major Histocompatibility Complex”” or “”MHC”” genes) on the clinical course of HIV infection. The results of this project will help us gain a more detailed understanding of the multiple genetic factors that affect the course of HIV infection, and help bring us closer to the potential incorporation of human genetic information into the clinical management and treatment of this disease. In addition, this research will be of relevance in the continuing efforts to develop a vaccine against HIV. Research such as this will help us develop and implement strategies for clinical management of HIV/AIDS and will therefore ultimately be of benefit to individuals living with HIV.

Alterations in cellular signalings in human diabetic vasculature contribute to diabetes-associated cardiovascular complications

The prominence of diabetes as a risk factor for cardiovascular complications has been rising in recent years, largely attributed to increased longevity combined with a non-active lifestyle and an unhealthy diet. Up to 80 per cent of deaths in diabetic patients are related to cardiovascular disease. The cardiovascular complications associated with diabetes occur when blood vessel walls thicken in response to changes in intracellular signaling within the vascular tissue. Dr. Ada Chung is identifying the underlying molecular mechanisms responsible for accelerated thickening of vessel walls and poor blood vessel formation, which lead to vessel blockage, hypertension, angina and other cardiovascular complications in patients with diabetes. Understanding these molecular mechanisms may be beneficial to medical innovations in diagnosis and treatment that can delay the onset and slow the progression of diabetes and its related cardiovascular complications.

Particulate Matter Air Pollution Induces Vascular Endothelial Dysfunction

Despite improvements in air quality over the past few decades, research shows that elevated levels of particulate matter air pollution (called PM10) are associated with an increase in cardiovascular disease (CVD) and death. More than 800,000 deaths a year can be attributed to PM10-induced CVD, including life threatening irregular heartbeats, atherosclerosis, heart attack and stroke. Diesel exhaust particulates are the major contributor to PM10 in most urban centres worldwide. But there is little evidence to describe how these particulates affect cardiovascular function. The endothelium is a monolayer of cells separating blood from the vascular wall, thus providing physical and biological protection. Importantly, endothelium plays a major role in protecting, activating and controlling cardiovascular function. Activation of endothelium is implicated in the development of atherosclerosis. Ni (Nicola) Bai is investigating whether exposure to diesel exhaust particulates induces dysfunction in these cells, causing the progression of atherosclerosis, and ultimately leading to heart attack and stroke. The findings should help develop interventions that minimize or prevent deaths associated with breathing polluted air.

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.

Characterization and Thrombogenic Contribution of Platelet Microparticles to Pathogenesis of Transient Cerebral Ischemic Attacks and Unstable Angina

Platelets are cells that augment blood coagulation to form blood clots which in some cases can restrict or halt oxygenated blood flow to the heart and the brain, causing a heart attack or stroke. Although drugs like aspirin have an anticoagulant effect that can decrease the chance and severity of a stroke or heart attack, these drugs do not entirely eliminate the risk. Platelets release mini-versions of themselves, called platelet microparticles (PMPs), into circulation, which are not affected by anti-coagulant drugs. The presence of PMPs in blood is a predictor of future blockages in the brain or heart, but their precise role is not clear. Hon Leong is investigating whether PMPs have the same clotting abilities as platelets to determine whether they cause the blood clots that lead to a stroke or heart attack. Hon is examining the structure of platelet microparticles and their ability to bind to other cells and clots. The results potentially may be used to develop more accurate blood tests to predict and detect strokes and heart attacks and, ultimately, new therapies that prevent platelets and PMPs from producing harmful clots.

An examination of injection drug use sites: the influence of social and physical context on drug-related harms and public health interventions

Injection drug use may result in severe health consequences including increased risk of viral infections such as HIV and hepatitis C, soft tissue infections, and drug overdose. Recently, with increasing attention being paid to the impact of environment on individual and public health, intervention efforts for injection drug users (IDUs) have moved beyond the modification of individual behaviour and focused on modifying the environments in which people use injection drugs. One recent and controversial example of this involves medically supervised injection facilities, where IDUs can inject pre-obtained illicit drugs under the supervision of health care professionals. William Small is studying and comparing three types of injecting settings in the Downtown Eastside: private injecting spaces (such as homes), public injecting spaces (such as alleys), and Vancouver’s supervised injecting facility. He is examining how the social and physical context of each setting influences the ability of injection drug users to employ HIV-prevention measures and safer injection practices. The findings of this research will build important knowledge about the health and HIV vulnerabilities of IDUs in the Downtown Eastside. Also, this research will provide information on the impact of current interventions, which may inform future interventions for addressing injection drug use.

To Each Her Own: Sex Work Typologies, Intimate Relationships, and their Impact on HIV Risk for Female Sex Workers in Vancouver's Downtown Eastside

The estimated 1,000 female sex workers in Vancouver’s Downtown Eastside (DTES) live in Canada’s poorest neighbourhood, characterized by deplorable housing conditions and high rates of hepatitis C and HIV infections. HIV prevalence is an alarming 26 per cent, according to a recent study of 198 female sex workers in the DTES. Although violence, poverty and social marginalization have been identified as putting these women at risk, we know very little about two of the defining issues that characterize sex work and make these women vulnerable to HIV: types of sex workers, and the intimate relationships women form with boyfriends and regular clients. Treena Orchard is exploring whether there is a link between a particular type of sex worker and relationship structure that places certain groups of women at greater risk for HIV infection. Her hypothesis is that women with an established sex work status are more likely to form lasting relationships and avoid high-risk sexual practices. Treena’s research is examining how different types of sex workers are identified and organized, and how these women construct and attach meaning to their intimate relationships, especially in relation to the issues of sexuality, health and trust. This study will use individual interviews, focus groups and social mapping to determine the broader social processes and health determinants that structure the HIV risk of these female sex workers. Examining the social organization of sex work and relationships in this context is critical to improving the women’s health status and developing HIV prevention programs that are population and gender-specific. As one of the few qualitative studies to address these issues among Canadian sex workers, this research will be relevant to other researchers, health authorities and – through their participation – the women themselves.

Examining the complex role of social, environmental and structural factors as barriers and facilitators for HIV risk and prevention among substance-using women in survival sex work.

Women engaged in survival sex work in Vancouver’s Downtown Eastside (DTES) face multiple vulnerabilities that directly enhance their risk of HIV transmission, including entrenched poverty, homelessness, repeated episodes of violence and assault, substance abuse, and social marginalization. In addition, the illegal, clandestine and largely unregulated nature of sex trade work in Canadian cities increasingly pushes street-entrenched women to the outskirts of society, limiting their means to protect themselves and access to supportive health services. Despite increasing evidence of gender differentials in new HIV infections facing women – particularly youth and women of Aboriginal ancestry – and extensive harm reduction and public health efforts focusing on illicit drug use in this community, little information exists about the complex social, environmental and structural factors that facilitate prevention, harm reduction practices, and access to care. Kate Shannon’s research will use participatory-action research methodologies to explore the social and environmental barriers and facilitators to HIV prevention among survival sex workers. While several individual factors have been shown to elevate HIV and STI (sexually transmitted infection) risk among female substance users in this setting, far less attention has been paid to the role of social and structural violence and power relations in facilitating HIV risk through both sexual and drug use pathways. Using social mapping, focus group discussions and interview-questionnaires, Kate’s research will aim to demonstrate the social and environmental factors that mitigate the HIV risk environment of survival sex workers, and in particular, the role of violence and power relations in the negotiation of HIV prevention behaviours among drug-addicted women and their intimate and working partners This research will provide valuable information about a population that has remained largely on the periphery of public health and harm reduction strategies and services. It is anticipated that the research will also foster capacity building among survival sex workers and help inform evidence-based policy and practice tailored to this population.