Investigating protein expression and localization in microsporidian parasites during infection

Dr. Ross Waller’s earlier research into the malaria parasite has contributed important information leading to a new array of drugs to treat the disease. Now he is studying microsporidia, a group of intracellular parasites that infect humans and animals. In particular, microsporidia infect immune-compromised individuals, causing encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach and intestines). The parasites have a remarkable method for invading host cells. This small, simple spore releases a harpoon-like tube that pierces the host cell. The parasite contents are then injected into the host through this tube, establishing the infection. Ross is identifying specific genes and proteins involved in the infection process, using genome sequences that have identified all the genes in two microsporidia. He is looking at the way proteins are prepared prior to and during the initial stages of infection. The results may provide new ways to combat these organisms.

A postdoctoral program to enhance planning and quality improvement initiatives in mental health through the validation of administrative mental disorder diagnoses

While a number of significant improvements in treatment of mental disorders have been made in recent years, gaps remain. For example, major depression is identified in only 50 per cent of people with the disorder when they visit their family doctor, and only half of those people receive appropriate treatment. Initiatives to address these gaps include programs that provide public and physician education and increase connections between care providers. However, it’s unclear how successful these initiatives will be due to a lack of data on the prevalence of mental disorders and whether people improve as a result of these programs. Dr. Paul Waraich is evaluating whether data routinely collected from hospital and physician visits, as well as medication prescriptions, are of sufficient quality to be used to evaluate changes in the care of major depression and other mental disorders. The research could greatly improve understanding of whether new mental health care programs are effective.

Analysis of specific host responses to pathogenic Escherichia coli infection

Escherichia coli (E. coli) bacteria cause much disease and death worldwide. However, little is known about the mechanisms these bacteria and others use to cause disease in their hosts. Specific virulence factors – strategies and molecules that enable the bacteria to cause infection – are needed for disease to develop. The bacteria inject these virulence factors into host cells, which affect normal cellular processes. Dr. Mark Wickham is using two pathogens, E. coli and Citrobacter rodentium, as a model to research how pathogens produce disease at the molecular and cellular levels. Understanding how this process occurs will address a gap in current knowledge, thus improving health and health services, and the research results could be applicable to other disease-causing organisms.

Baseline HIV RNA and mortality after the initiaton of HARRT: Exploring the mechanism that explains the association

Before triple-drug antiretroviral therapy was developed to treat HIV, certain levels of HIV ribonucleic acid (RNA) in the blood were strongly associated with progression of the disease. However, there has been a great deal of uncertainty about the clinical relevance of HIV RNA levels since the therapy was introduced. Recent studies have produced conflicting results about the association of HIV RNA levels with survival or death for individuals with HIV. But these studies did not assess patient adherence to triple-therapy treatment. Dr. Evan Wood is using data from the BC Centre for Excellence in HIV/AIDS Drug Treatment Program to research the association between HIV RNA levels and survival after beginning triple-drug antiretroviral therapy. He is also investigating the relationship between HIV RNA levels and factors such as non-compliance with triple therapy treatment. The findings could be used to adapt provincial guidelines for HIV/AIDS treatment.

Who “crashes” onto dialysis? Impact of social determinants of health on renal patients’ access to dialysis treatment

Despite the fact that chronic kidney disease almost always presents warning signs, 30-50 percent of new renal patients in BC “crash” onto dialysis or are referred late for assessment of kidney disease. Both scenarios are associated with increased morbidity (severity of symptoms), increased hospital stays, reduced opportunities for more ambulatory modes of care, such as peritoneal dialysis or early kidney transplant, and increased mortality (incidence of death). There is much to be learned about the range of possible determinants that may influence renal patients’ ability to access treatment. Nancy Blythe will investigate the social determinants of health of 1300 renal patients who initiated dialysis in BC in 2001-2002. Her aim is to determine whether certain social structural barriers in society (availability of social support, adequate income, etc.) constrains patients from seeking treatment before their chronic illness advances to an acute stage, resulting in late referral to the health system or the onset of dialysis under emergency conditions. Subsequently she will study whether those same social barriers and suboptimal initial access negatively influence ongoing access to dialysis as well as morbidity and mortality. It is anticipated that the research results will contribute to better ways of assisting renal patients to obtain optimal access to this life support treatment.

Addressing needs through action: what can be done to help HIV positive kids (8 and up) to ""live positively"" in BC within their broader healthcare community?

There is little published information about Canadian children with HIV especially about the health-related needs of adolescents. Yet it is during this period when they begin dealing with issues such as disclosure, psychosocial therapy, HIV prevention and sexual health, that support is most needed. Sarah Fielden is examining the health needs of children with HIV and developing strategies to meet them. Her research involves conducting focus groups with children and adolescents, families and service providers to capture a range of perspectives on this issue, and to specifically explore factors in the health system and community that allow children and adolescents to “live positively”. Sarah’s aim is to help improve the health and health care of children with HIV, and assist health care providers, academics, organizations and families in developing effective, age-appropriate interventions.

Role of culture, rumination, and anger suppression on stress recovery

Researchers have identified several factors, including chronic hostility and a tendency to suppress emotion, that may predispose people to stress-related illnesses such as gastrointestinal problems and cardiovascular disease. A compounding factor is that cultures differ in the degree to which they expect members to show or suppress emotion, such as anger; yet little is known about the impact of culturally-mandated suppression of emotion on stress-related illnesses. Jeremy Anderson is examining how cultural and psychological factors may contribute to stress-related illnesses. His study involves provoking anger from two culturally distinct groups of participants, allowing just one of the groups to express the anger, and then comparing the stress responses from the groups by measuring blood pressure, heart rate and the stress hormone cortisol. The research will improve understanding of how culture affects stress-related illnesses and may also help in the design and targeting of healthy interventions for specific groups.

The contribution of hepatic ABCA1 to HDL levels and composition, and suceptibility to atherosclerosis

Coronary artery disease is a leading cause of death among Canadians. High cholesterol has been identified as a major risk factor for the disease. However, there are two kinds of cholesterol: LDL, the so-called “bad” cholesterol that has been linked to coronary artery disease, and HDL, the so-called “good” cholesterol that has been linked to lower incidence of heart disease. Currently, the medical community’s focus is on decreasing LDL levels, but more than fifty percent of people with premature coronary artery disease have low levels of HDL. A gene called ABCA1 has been identified as critical in the production of HDL, but there is still uncertainty about its function. ABCA1 exists in most tissues of the body, but some tissues – notably the liver – are particularly rich in it. Liam Brunham is investigating the role of ABCA1 in the liver and in the production of HDL. Learning about this gene will increase understanding of how the human body produces and uses cholesterol and how it responds to different diets.

The role of the stem cell antigen, CD34, on mature murine mast cells

In earlier research supported by a MSFHR Masters Trainee Award, Erin Drew disproved theories that CD34, a cell surface protein, was specific to immature blood cells. She found CD34 on immature blood cells, but also on cells lining the blood vessels and on mast cells. Mast cells are known to play a pivotal role in allergic and asthmatic responses. Erin’s work now focuses on CD34’s function in mast cells and how the protein prevents inappropriate adhesion to other cells and tissues. These enquiries will increase new knowledge on how blood cells move around the body and how mast cells can invade tissues and respond to allergens. Ultimately, Erin hopes her work will lead to the identification of targets for the treatment of allergies and asthma.

Factors impeding the success of HIV antiretroviral therapy today: Genetic variation, viral evolution and drug resistance, and cellular reservoirs of HIV

Revolutionary new therapies for HIV/AIDS introduced in the mid-1990s have helped to dramatically reduce deaths resulting from HIV infection. However, despite these advances, the prospect of a cure for HIV infection remains a distant goal. Drawing on the expertise at the BC Centre for Excellence in HIV/AIDS, Zabrina Brumme is researching the genetic factors that may influence HIV disease progression and individual response to therapies, with the goal of better optimizing and tailoring HIV therapy to each patient. Zabrina will also study “viral reservoirs,” cell types that are believed to “hide” HIV for long periods of time over the course of the infection. This project could lead to anti-HIV therapies directed specifically against viral reservoirs, increasing the chance of survival and improving the quality of life for HIV patients.