Characterizing the role of granzyme B in atherosclerosis and hair loss in apolipoprotein E knockout mice

Cardiovascular disease is the leading cause of death in Canada. Atherosclerosis is a cardiovascular disease, in which the inside of blood vessels contain fatty growths known as plaques. Over time, these plaques become unstable and can break, resulting in blockage of blood vessels. This can lead to heart attacks, strokes and limb loss. Wendy Boivin’s research explores what makes a plaque develop, grow, and become less stable. She is focusing on a protein called Granzyme B, which is known to cause plaques. What is unknown is which of two possible approaches Granzyme B uses to induce plaque formation and atherosclerosis: either by entering blood vessel cells and killing them, or by breaking down structural proteins in the blood vessel. Wendy Boivin is studying the role of perforin, a protein that is required for Granzyme B to enter into blood vessel cells. By conducting a study that observes what happens when perforin is removed from blood vessels, she can pinpoint the pathway Granzyme B uses to cause atherosclerosis. Ultimately, this study may contribute to new therapeutic targets for combating this disease.

The Genetics of Asthma, Atopy and Allergic Diseases

My research focuses on trying to identify why some children get asthma and others do not. By identifing specific environmental and genetic risk factors and determining how they work together to predispose children to developing asthma and other allergic diseases we can design better treatments. Studies have found a 1-in-5 risk of developing asthma if one parent has asthma. The odds rise to 2 out of 3 if both parents have asthma. However, in itself, a genetic predisposition does not ensure that asthma will develop. Asthma and allergic disease are the result of both genetics and the environment. The interaction between a genetic disposition and environmental factors is key in the development of – or in protecting against- asthma. I will use information from 250 French Canadian Asthma Families and two additional birth cohorts, and information from the town of Busselton Australia in my research. Home visits were conducted for all the families and children to collect information on environmental factors such as family history, number of children, parental occupations, daycare, pets, dust samples, infections, hospitalizations and medication usage. After reviewing the literature we have found 162 genes which may predispose children to developing asthma and we will be looking at these genes in conjuction with other environmental factors to try and better understand why some children develop asthma and others do not. Using statistical models we will look at what genetic and environment factors best explain why some children develop asthma and others do not. We will then do further laboratory experiments to try and identify these factors work together.

An interventional HIV research program to reduce transmission and enhance antiretroviral treatment outcomes among highly marginalized populations

The prevalence of HIV infection among injection drug users and other highly marginalized groups is a significant health issue in Canada. Vancouver’s Downtown Eastside (DTES) is particularly hard hit, with HIV prevalence rates estimated at 25 per cent. These high rates of HIV infection persist in spite of efforts to reduce HIV transmission through various prevention programs, harm reduction strategies, treatment facilities and community law enforcement. HIV prevention strategies and treatment therapies that are effective among other populations have not had the same success in the most vulnerable and marginalized members of society. As an HIV clinician and researcher in the DTES, Dr. Mark Tyndall’s research takes three streams: Observational Cohort Studies: Identifying trends in risk behaviors, drug use patterns, HlV/Hepatitis C rates, social changes, law enforcement initiatives, and the impact of harm reduction interventions on key health indicators; Antiretroviral Therapy: Developing and evaluating strategies and programs that enhance the uptake, delivery and sustainability of antiretroviral therapy to marginalized groups; and Clinical trials research: Advancing Vancouver as a centre for clinical trials research for the evaluation of candidate HIV vaccines and other novel therapies among marginalized groups. Together, Dr. Tyndall’s studies will allow for evidence-based decision-making and improved health outcomes for marginalized groups living with HIV in the DTES and other urban areas in BC.

Interdisciplinary Team Generating Research on Complex Patients to Develop Innovative Solutions

This award funds the creation of a transdisciplinary team studying health issues of complex patient groups with multiple illnesses, and varied ethnicities and socio-economic backgrounds. The goal is to examine the health status and trajectory of these patients by integrating research about the social determinants that affect their health, such as education, housing status, and income level.

An Internet-based self monitoring intervention for patients with chronic heart failure

In 1997, congestive or chronic heart failure (CHF) was the primary cause of death in British Columbia and in 2000, it was the most common cause of hospitalization for Canadians over the age of 65. Multidisciplinary interventions, including education, follow up and self-management strategies have been shown to improve quality of life and decrease subsequent hospital admissions among people with CHF. However, up to 50 per cent of hospital readmissions for CHF occur because patients have not learned to manage and monitor their condition effectively. Biljana Maric’s research is investigating the feasibility of Internet-based self-monitoring for CHF patients. Participants will log on to the study website each morning, enter their current body weight and answer five questions about their health status and any symptoms they are experiencing. A nurse will log on to a secure database to monitor responses and follow up with participants when responses trigger an alert. Biljana’s study will examine patient and staff uptake, and assess the impact of the program on patient quality of life and self care. If adopted, Internet monitoring of heart patients could decrease the health care costs associated with heart failure readmissions, alleviating some of the financial burden on the health care system while improving patient health outcomes.

An Empirical Test of Rational Polydrug Addiction

The economic model of rational addiction was a breakthrough in the economic theory of consumption of addictive substances. This model’s aim is to reliably estimate an addict’s change in consumption of an addictive substance due to a change in the drug’s price or the price of another drug to which the individual is addicted. Polydrug abuse within populations of heroin addicts has been observed within health services research literature for some time. Suggestions have been made to target treatment interventions and outcome assessment to multiple drugs, rather than a single drug in clinical trials involving substance abusers. Despite this, relatively little epidemiological research has been carried out to evaluate the effectiveness of different modes of treatment for drug abuse in polydrug addicts. Bohdan Nosyk is researching whether individuals addicted to more than one substance (e.g. heroin and cocaine) display some association in their consumption patterns of these substances. If there is a significant association in consumption, focusing treatment on one addiction may be ineffective given the increase in consumption within the other (untreated) drug addiction. This study will survey individuals addicted to multiple drugs residing in Vancouver’s Downtown Eastside to determine the relationship between illicit drug prices and consumption. Research into the addicted illicit drug consumer’s behaviour – in particular, how the consumer substitutes between substances and which drugs tend to complement one another – will provide policy-makers with evidence on which to base future directions in the treatment for addictive substance abuse.

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.

Why are women at increased risk of chronic obstructive pulmonary disease and lung cancer? Is inflammation the missing link?

Chronic obstructive pulmonary disease (COPD) is a term for a group of respiratory diseases—such as chronic bronchitis or emphysema—in which there is chronic obstruction of airflow through the airways and lung damage. In Canada, despite the fact that more men smoke than women, the rates of chronic COPD and lung cancer in women are expected to exceed those in men within the next five years. Dr. Donald Sin is investigating why women seem more susceptible than men to COPD and lung cancer. His research proposes that women mount a more vigorous inflammatory reaction to cigarette smoke and environmental irritants than men, resulting in chronic lung and systemic inflammation that can lead to COPD and in some cases, lung cancer. Dr. Sin is comparing sex-related differences in the relationship between lung and systemic inflammation and the development of lung cancer. His research will not only shed light on why women are more susceptible to COPD and lung cancer compared to men, but may also be an important foundation for developing medications to reduce the risk.

Lung inflammation induced cardiovascular disease

There is substantial epidemiological evidence that inhalation of air pollution particles results in increased morbidity and mortality from heart conditions, such as heart attacks, cardiac arrhythmia, and heart failure. Recent research has shown that air pollution causes the development and progression of atherosclerosis, the underlying disease in vessels responsible for stroke and heart attacks. However, the biological mechanisms of air pollution-induced heart disease remain unclear. Dr. Stephan van Eeden is exploring at the cellular level the connection between the inhalation of air pollution particles and the development and progression of blood vessel disease (atherosclerosis). His hypothesis is that chronic lung inflammation caused by exposure to particulate matter air pollution and cigarette smoke cause a persistent, low-grade systemic inflammatory response that contributes to the development of atherosclerosis. He is conducting a series of studies to determine whether inhalation of air pollution particles destabilizes atherosclerotic plaques and trigger clot formation. This information will provide researchers and policy makers with a greater understanding of the adverse effects of air pollution on individuals’ health.