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.
Year: 2001
Cell adhesion and signaling in oncogenesis
The main objective of my research is to understand the molecular basis of how cancer progresses and to use the knowledge to identify new cancer therapies. To achieve this, my research team is studying receptors found on the surface of most cells that cause them to attach to other cells. We want to determine how the receptors communicate information they detect on the outside of the cell to the inside of the cell. We have identified proteins that interact with these receptors on the inside of the cell and are responsible for transmitting information to other parts of the cell to control cell division, cell death, cell differentiation and cell movement. We are focusing on one protein – Integrin Linked Kinase (ILK) – whose function is tightly regulated in normal cells, where its activity rapidly turns on and off. But in cancer cells, ILK is on all the time, leading to increased cell division, decreased cell death and increased cell movement. We have determined that ILK is at least partly responsible for the abnormal behaviour of cancer cells, and ILK activity is considerably elevated in many types of cancer. We have also identified specific chemical inhibitors of ILK activity, which are currently being evaluated in pre-clinical trials. The results to date show these inhibitors are effective in blocking growth and spread of tumours. ILK is present in many tissue types, and it is likely that it plays a critical role in the development and function of these tissues, and in other diseases of chronic inflammation such as arthritis, asthma, kidney disease and heart disease. To investigate this further we are using genetic techniques to alter ILK expression and function in a tissue-specific manner. Such studies will lead to a better understanding of the role of ILK and related proteins in nomal and diseased tissues.
Origin and evolution of intracellular parasites apicomplexa and microsporidia
Apicomplexa and microsporidia are two groups of parasites that infect a broad range of animals, including humans. Apicomplexa cause serious diseases such as malaria and encephalitis. Traditionally, microsporidia were not prevalent among humans. However, microsporidia are increasingly becoming a problem in people with impaired immune systems. The relationships of these parasites to other organisms and how they evolved are not clearly understood. Yet recent molecular studies have revealed surprising evolutionary histories for both groups of parasites. Apicomplexa evolved from an alga, an unusual origin for a parasite. Microsporidia were originally believed to be simple, single-celled organisms that were not highly evolved. But we now know that microsporidia have evolved from fungi. I am studying the evolution and biology of apicomplexa and microsporidia to learn how they developed into parasites and how they function. This research may uncover weaknesses in the parasites that can be exploited to develop new treatments for disease involving herbicides or fungicides that would not have been considered earlier.
Functional imaging of neuronal Ca2+ in vivo and in vitro brain slice
My research lab uses fluorescence imaging technology combined with electrophysiological measurements to study problems with the transmission of information in the brain. Such problems are the foundation of numerous brain disorders including schizophrenia, depression and Parkinson’s disease. We need a thorough understanding of the brain’s communication process to understand and develop treatments for these disorders. Brain function depends on the activity of neuronal circuits, which are formed by thousands or millions of neurons (nerve cells) that communicate with each other at points of contact called synapses. Neurons communicate when the pre-synaptic neuron releases a chemical transmitter that diffuses across the synaptic space and binds to receptors on the post-synaptic (receiving) neuron. The receptors are often located on branches of the neuron called dendrites. My research examines the factors that control the amount of chemical transmitter released, and in particular, the regulation of release by calcium ions in pre-synaptic neurons. Transmitter release is stimulated by an influx of calcium into the pre-synaptic neuron. Calcium influx is controlled by changes in the electrical potential of the pre-synaptic neuron that regulate the opening and closing of the voltage sensitive “”gates”” of calcium permeable pores in the neuron’s surface. By changing calcium influx and accumulation in neurons, the strength of the synaptic connection can be varied to adapt to new conditions or tasks. Using fluorescent dyes that are sensitive to calcium, we monitor calcium in pre-synaptic neurons at the same time that we measure synaptic transmission electrically. Our laboratory has the unique capability to make these measurements in an intact living mammalian brain. We are investigating how activity in the pre-synaptic neuron and substances such as dopamine or serotonin control transmitter release by their effects on calcium, and the biochemical machinery that release transmitter in response to calcium. We also are studying how the signal reception at the post-synaptic neuron is regulated by electrical properties of the dendrites.
The role of the hematopoietic progenitor antigen, CD34 on mature mast cells
A study that Erin Drew took part in revealed some surprising insights about the mysterious CD34 protein. Contrary to the predominate belief that this protein is absent on mature blood cells, this study demonstrated that CD34 is present on mature mast cells. These cells play a major role in the development of asthma and allergies by releasing strong chemicals such as histamine into tissues and blood. In her Master’s research, Erin further investigated the role of CD34, and a similar protein CD43, on mast cells. Her research suggests that CD34 blocks inappropriate cell adhesion, and that CD34 and CD43 play an important role in the appropriate migration of cells into tissues. Erin hopes this work could lead to new drug treatments for asthma and allergies, as well as contribute to the emerging use of stem cell transplantation in treatment of diseases.
The role of BDNF in progesterone and estradiol effects on cell proliferation, survival and cell fate in the dentate gyrus of adult female rats following contusion
Research has revealed that adult humans and all other mammals are unique in their ability to generate new brain cells as part of a process called neurogenesis. After a traumatic injury, estrogen and progesterone (female steroid hormones) and the Brain Derived Neurotrophic Factor (BDNF) protein help the brain recover. Jennifer Wide’s Masters research focused on the interaction between estrogen and neurogenesis, and in particular, the effects of chronic estradiol treatment on neurogenesis. Based on previous research, she hypothesized that changes in neural structure affect cognition, such as through working memory (also known as short-term memory). She studied, therefore, the effects of estradiol treatment on acquisition and reacquisition of working memory. The research demonstrated that chronic estradiol treatment has a significant differential effect on working memory, especially in low doses. Increasing understanding of neurogenesis will bring researchers closer to the goal of replacing lost cells throughout the brain and have a major impact on neurotrama and neurophsychiatric disorders.
Bone Health in Adult Women: The Relevance of Dietary Restraint, Cortisol Excretion and Nutrition-Related Stress
Candice Rideout is fascinated with bones. Despite a perception that bones are static once we’re fully grown, they’re actually ever-changing, which intrigues Candice. She is also interested in how nutritional behaviours affect bone health. The two interests come together in her research. Candice, who transferred from a Masters to PhD program, is examining bone health in adult women, looking specifically at possible links between dietary restraint, stress and bone density. The first phase of the research involved a broad survey of more than 1000 healthy postmenopausal women. Phase II will be an intensive study of a sub-group of women from the first phase, in which Candice will investigate the hypothesis that high levels of dietary restraint (the perception that one is constantly monitoring and attempting to limit food intake in an effort to achieve or maintain a desired weight) is associated with increased stress and possibly lower bone density. The diet and physical health of Phase II participants will be studied over a three-month period. Candice hopes this research will contribute to a better understanding of how nutritional factors relate to women’s health and wellbeing.
Heroin and Methadone Maintenance Treatment: Accessibility, Barriers and Quality of Life issues for Women in the Downtown Eastside, Vancouver, British Columbia
Magdalena Recsky developed her passion for epidemiology while working summers as a research assistant at the BC Centre for Excellence in HIV/AIDS. She put that passion into practice through her Masters research, which explored issues surrounding methadone dosing, satisfaction with methadone doses and associated HIV-risk behaviours. Using existing data, she investigated the barriers women face in accessing methadone maintenance programs, which led to a broader study into methadone dosing. Results from the studies and a literature review demonstrate that high patient satisfaction with methadone treatment can potentially decrease certain HIV-risk behaviours. The results also highlight the importance of physician-patient relationships in the treatment of heroin addiction and the importance of individualizing methadone treatment. Although certain methadone doses are pharmacologically required to curb heroin withdrawal, the research shows that once that dose is reached, patient satisfaction with treatment may be more important in positively influencing methadone treatment outcomes. Ultimately, she hopes this research will contribute to improvements in methadone treatment programs that more effectively address the needs of specific population groups, such as those involved in high HIV-risk behaviours.
Regulation of the transcriptional activator, beta-catenin, by the B cell receptor
Sherri Christian is studying a process that’s integral to the immune system: the development of B cells that produce antibodies – immune cells that attach to and destroy infectious microbes and other harmful agents. Signals from within and outside B cells direct the multi-stage process by which these cells develop. Christian is investigating the nature of these signals and specifically examining the regulation of a protein called beta-catenin. The protein’s importance in the development of other cell types suggests it may play a similar developmental role in B cells. Christian hopes that increasing understanding of B cell development will ultimately lead to therapies for prevention of disease, such as cancer, which occurs when the normal process of cell development goes awry.
Comparative and functional genomic analysis of a gene dense, GC rich region at chromosome 7q22 associated with myeloid leukemias and male infertility
Michael Wilson’s doctoral research focuses on a fragile region of the human genome, 7q22, which has been linked to leukemias, hemochromatosis (a genetic disease that causes excessive build-up of iron in body tissues), male infertility and schizophrenia. Besides preparing a detailed map of all 7q22 genes and elements that regulate their expression, Wilson is also working with a bioinformatics group at Penn State to design a web-based program that interactively displays the gene sequence data. He is also investigating the function of two specific genes, including one that plays a role in fertility. Wilson hopes the research will provide essential information for narrowing in on cancer and schizophrenia-related genes, and also provide insight into male infertility.