Molecular and genetic mechanisms of obstructive lung disease

Asthma and chronic obstructive pulmonary disease (COPD), also known as emphysema, are major causes of disease and death worldwide. The prevalence of asthma is increasing, and in some Canadian communities, up to 20 per cent of children are affected. Globally, emphysema ranks twelfth as a cause of lost quantity and quality of life, and is projected to rank fifth by the year 2020 as smoking and air pollution increase around the world. Significant gaps exist in our understanding of these disorders, and while limited therapies are available, none is universally effective or without side effects. I am examining genetic susceptibility for asthma and COPD. Many people smoke and are exposed to allergens, but only a small percentage develop asthma or COPD. For example, cigarette smoking is the major risk factor for COPD, but only 10-20 per cent of smokers develop the disease. Similarly allergy is common, but only some individuals develop asthma. The evidence suggests that susceptibility runs in families, but few genetic risk factors have been identified. My research team is using a registry of lung tissue from patients who have had lung surgery, as well as DNA from large groups of individuals who have these conditions, to identify the genes that account for this susceptibility. We want to discover the molecular mechanisms that cause asthma and COPD, and to predict if an individual’s genetic makeup puts them at increased risk for these disorders. Ultimately, this research should increase understanding of these disorders and contribute to the development of new diagnostic tests, preventative strategies and therapies.

Investigation of the apolipoprotein C-II activation site of human lipoprotein lipase

The enzymes hepatic lipase (HL) and lipoprotein lipase (LPL) play a key role in the metabolism of cholesterol and fat circulating in the blood stream. However, their specific role and capacity to offer protection from heart disease are unclear. My research will identify the parts of each enzyme responsible for performing different functions. This knowledge will more clearly define how these enzymes influence the metabolism of cholesterol and fat and the development of cardiovascular disease. I am combining parts of HL and LPL to create new enzymes that will highlight the differences between the original enzymes’ functions. For example, a fundamental property of enzymes is how they are activated. We know a particular protein that does not activate HL does activate LPL. I will put the portions of LPL we think are responsible for activation into HL to test whether HL is activated and confirm that this part of LPL causes activation. When we know how these enzymes work to regulate and control the level of cholesterol and fat, we will understand their relationship with cardiovascular disease, and should be able to develop enzyme inhibitors or activators to improve cardiovascular health.

Epidemiological and population-based investigations of persons infected with HIV

I am a demographer who is currently involved in observational research into the impact of antiretroviral therapy on quality of life and life expectancy of persons with HIV disease in British Columbia. I am also interested in issues regarding access to antiretroviral therapy in developing nations. My most significant contributions to HIV research include: Studies monitoring seroincidence and determinants of HIV infection and risk behaviour among gay and bisexual men In a natural history study of HIV-positive gay and bisexual men, we demonstrated that lower socioeconomic status decreases the length of survival. Low income was significantly associated with shorter survival from HIV infection to death, even after adjustment for CD4 count (which measures immune suppression in persons with HIV), age at infection, year of infection and use of HIV therapies and prophylaxis. Studies measuring the impact of HIV infection on population health My primary goal in the area of population health research has been examining the impact of HIV on patterns of mortality, migration and hospitalization in Canada. One study I conducted showed that although there are barriers to widespread HIV treatment, limited used of antiretroviral therapy could have an immediate impact on South Africa’s AIDS epidemic. A second study demonstrated that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources. Studies evaluating the impact of antiretroviral therapy on the health and well-being of persons with HIV disease One of my studies demonstrated a significant reduction in mortality and AIDS-free survival for HIV infected individuals who initiated therapy with regimens including stavudine or lamivudine compared to those who initiated therapy with regimes limited to zidovudine, didanosine and zalcitabine.

Determinants of excessive waiting for cardiac catheterization and revascularization in British Columbia

Cardiovascular disease is the most common cause of morbidity and mortality in British Columbia and Canada, accounting for one-third of all deaths and over one-half of deaths among persons aged 50 years and over. The economic burden of cardiovascular disease is enormous. In BC in 1998, the most recent year for which there are reliable figures, the annual direct costs were approximately $1.1 billion and the indirect costs were estimated at $3 billion, making this the most costly of any category of diseases in the province. I have developed a research program for the systematic investigation of the delivery and outcomes of cardiovascular diagnostic procedures, and medical and surgical care in BC and the rest of Canada. The projects in the research program largely involve using linked administrative and clinical databases. One project of particular interest in BC is the issue of wait times for cardiac bypass surgery. In Canada in the late 1980s, a dramatic increase in referrals for coronary artery bypass surgery outstripped capacity for this procedure. The Ontario government expanded capacity and developed criteria for placing patients on cardiac surgery waitlists. Capacity was increased in BC, but patients were put on the waitlist in an ad hoc manner, which continues today. I am conducting a large study to examine waitlists for cardiac operations in BC. The official wait time is the interval between being booked for an open heart operation and actually having the procedure. There is evidence this wait has decreased in the past two years. I am investigating whether there is a true decrease or if patients are waiting earlier in their process of care, before the operation is booked. This study will compare wait times in BC to benchmarks established in Ontario, identify the proportion of patients who wait longer than recommended by medical guidelines, examine the characteristics that predict longer wait times, and propose ways to shorten the waitlist for people waiting the longest. The results of this research will help determine whether we need a more formal system for managing cardiac resources in BC.