The unprecedented investment in biomedical research during the past 50 years has resulted in many important advances in health care knowledge. However, the successful and timely integration of these advances into clinical practice remains a major challenge, especially in primary care and community settings. There is growing recognition that one of the obstacles to translating knowledge into clinical practice may be the knowledge itself, and how, where and by whom it was generated. Often, research knowledge is created in academic settings with little opportunity for involvement or input from primary care providers, community partners or patients. Dr. Janusz Kaczorowski aims to generate more high quality research evidence by end-users themselves, and under clinical conditions that closely resemble real life primary care and community settings. He believes that such an approach will help develop evidence that is more relevant to healthcare professionals working in these setting, which will speed up the knowledge transfer process. Building on his previous work across North America, Kaczorowski’s research focuses on the development of innovative primary care and community-based strategies for chronic disease prevention and management that will have a positive impact on the lives of British Columbians and Canadians. Strategies include collaborative ways to involve, in addition to family physicians, community caregivers (such as pharmacists), volunteer peer health educators, community-based organizations and patients in the research process.
Research Location: University of British Columbia - Point Grey
Development of an Integrated Risk Assessment and Risk Management Tool for Health Care in BC, Phase 1 – assessment of chemical exposure hazards encountered by health care workers in BC
There are more than 80,000 health care providers working in BC. They work in complex and demanding environments where they may be exposed to numerous potential health hazards, including those that are chemical (e.g. drugs or cleaning agents), biological (e.g. bacteria or viruses) and physical (e.g. noise or radiation) in nature. Dr. George Astrakianakis focuses on understanding the many factors that determine the potential for exposure to health hazards among health care workers, and how to best mitigate their associated risks. In the initial phase of his research, he is identifying the specific chemical exposures commonly encountered in the healthcare workplace, assessing the risk to health for healthcare providers, and defining appropriate exposure control measures. In subsequent phases, he will assess biological and physical hazards, and implement and evaluate control strategies. Much of Astrakianakis’ data will be drawn from surveillance information collected by the Occupational Health and Safety Agency for Healthcare, which supports BC’s health care industry in part by monitoring information on occupations, exposure incidents and injuries among the Province’s health care professionals This information will form the basis for creating a job exposure matrix (JEM), which will be used to map exposure levels to occupations and eventually to provide risk estimates. The ultimate goal of this project is to design and implement appropriate exposure control strategies — such as technology, policy and training — in health care settings and to evaluate their effectiveness in mitigating risk to health care providers.
Determination of cleavage site specificity of matrix metalloproteases by assay of a peptide library generated by enzymatic digest of a complete or partial proteome
Mass spectrometry is a technique for separating and identifying molecules based on mass. It’s an important tool in proteomic investigations, the analysis of the whole set of proteins expressed in a cell. Recent advances in mass spectrometry have enabled the identification of thousands of unknown nd uncharacterized proteins. Many of these proteins are proteases, enzymes responsible for splitting specific peptide bonds (primary links of protein structures). Patrick Beaudette is studying a protease family known as matrix metalloproteases (MMPs). MMPs regulate a variety of cell processes, from the degradation of structural proteins to the activation and inactivation of cell signaling pathways. Proteins proteolytically processed under these circumstances can have implications in a variety of disease symptoms, ranging from inflammation to tumor growth. Beaudette’s research focuses on identifying the substrates (molecules upon which enzymes act) that a particular MMP protein splits, and the mechanism by which it locates these substrates within the cell. The research may lead to a fuller understanding of the function of the MMP family of enzyes and the role it plays within a cell. The findings could contribute to the design of inhibitors for MMPs for use in therapy of cancer and other conditions.
Discovery of immunogenic Salmonella peptides by immunoproteomics
Salmonella bacteria can contaminate food, causing Salmonellosis, a disease with symptoms such as diarrhea and abdominal cramps. Although treatable with antibiotics, the incidence and severity of Salmonellosis has increased over the last ten years, partially due to increased antibiotic resistance by some strains of the bacteria. Consequently, other methods of treatment or prevention are needed to better control these infections. Queenie Chan is investigating the potential to develop a vaccine for Salmonellosis. Vaccine design varies in difficulty, depending on the nature of the infectious agent. In the case of Salmonellosis, dendritic cells take up bacteria in the body and break the protein components down into small pieces (peptides) on the surface of the cells. These fragments retain the identity of the original bacteria. In theory, injecting bacterial fragments identical to those found on the surface of dendritic cells will prompt an immune response against the bacteria, without an actual infection. Chan is using an instrument called a mass spectrometer to simultaneously assess hundreds of these peptide fragments to determine which peptides elicit an immune response. Chan hopes these peptides will provide the foundation for creating a vaccine against Salmonellosis, thereby avoiding the use of antibiotic drugs that help perpetuate the growth of antibiotic-resistant bacteria.
Effect of long term air pollution exposure on childhood respiratory diseases in the Georgia Basin: A cohort study
Asthma is the most common chronic disease in childhood. Long term studies indicate predisposition to asthma develops in the first three to five years of life. Recent evidence suggests exposure to air pollution from traffic is associated with new cases of asthma. However, the long-term impacts of air pollution exposure and whether this exposure causes asthma are unclear. Nina Clark is investigating the association between exposure to air pollutants and childhood respiratory diseases in southwestern BC. Using the BC Linked Health Database that connects various data sources to provide individual level health outcome data, Clark is tracking the exposure and health outcomes of approximately 120,000 children who were born in the region over the four-year period beginning in 1999. She will examine resources including maps detailing air pollution concentration, medical services plan billing records and hospital discharge records. Clark will also look at variables such as age, gender, birth weight and socioeconomic status. She hopes her research will lead to targeted reductions of air pollution exposure, such as zoning or land use restrictions to limit exposure of children, and help provide focus for future interventions and policies.
Remaining patient: Transforming the practices of health care to promote positive outcomes for teen mothers and their children
Teen pregnancy is a health issue affecting Canadian youth, particularly vulnerable teens. Unfortunately, teen mothers typically do not access health care regularly which hinders their ability to receive necessary information about both prenatal and maternal health. Without effective and early intervention, young mothers and their children have ongoing health, social and education issues that strain the health care system. While researchers have differing opinions about the impact of age on these health outcomes, most research defines teenage pregnancy as a health and social problem. Genevieve Creighton is studying whether the concept of teen mothers as “ill” stigmatizes teen mothers, making them reluctant to access the health care system for fear of being judged by health care workers and educators. Creighton is working with pregnant and parenting teens and their health care providers to determine whether certain attitudes and practices have a negative impact on their relationships and how these can be transformed. This information could help health and social service providers design more effective programs for teen mothers and other vulnerable populations.
The role of Na+/H+ exchangers (NHEs) in pH regulation and brain function
The regulation of pH (a measure of acidity or alkalinity) is a highly sophisticated and tightly controlled process that is extremely important for proper brain function. Abnormal fluctuations in the pH of neurons (nerve cells) may be involved in the development of many neurological disorders such as epilepsy. Sodium-proton exchangers (NHEs) are membrane proteins that play an important role in maintaining and regulating cellular pH. Two forms of these proteins in humans, NHE1 and NHE5, are found at high levels in the brain. Graham Diering is investigating the exact function of NHE5, the only NHE that occurs almost exclusively and at high levels in the brain. NHE5 has been linked to familial paroxysmal kinesigenic dyskinesia (PKD), a neurological movement disorder. However, the precise involvement of the protein in PKD, and its role in proper brain function, are unknown. Diering is researching NHE5 in different brain structures, including mature and developing tissue, and examining the protein at the cellular level to determine where it may be active in nerve cells. An enhanced knowledge of the mechanisms in nerve cells that regulate pH could increase understanding of the factors that govern brain function, both in the normal and diseased state. As well, an analysis of specific molecules involved in this process could contribute to development of diagnostic and therapeutic strategies for treatment of neurological disorders.
Elucidating the signal transduction pathways by which the host defence peptide LL-37 initiates immunomodulatory responses by bronchial epithelial cells
The immune system must strike a balance between fighting off illness and infection and damaging tissues in the body. If the balance swings too far in either direction, the results can be disastrous. Over-stimulation of the immune system can result in tissue damage, low blood pressure, organ failure and death. A good example is toxic shock syndrome, which occurs when an enormous overreaction by the immune system triggers a rapid drop in blood pressure, leading to multiple organ failure. Mortality is as high as 30 to 40 per cent Researchers recently suggested that this type of reaction may explain, in part, why the 1918 flu epidemic was so deadly. A protein called LL-37 is involved in healing wounds and growing new blood vessels, a process that is vital for repairing damaged tissue. Niall Filewod is investigating whether or not LL-37 can help calm an activated immune system. Thus diminishing the effect of excessive immune responses and protecting the body from toxic shock. If so, this research could lead to new drugs to treat conditions ranging from sepsis to arthritis that result from immune system reactions gone awry.
Heme binding and transport by the Staphylococcus aureus Isd system
Staphylococcus aureus is a bacterial pathogen that is of considerable medical concern. Though it normally lives externally on humans or animals, S. aureus causes problems when it is introduced into breaks in skin or mucosal surfaces, enabling it to invade the surrounding tissues and move into the blood stream. S. aureus poses an especially great threat in the hospital setting where it is one of the most commonly acquired bacterial infections and a serious cause of disease and death. The emergence of multidrug-resistant “superbugs” has highlighted the potential threat S. aureus poses in the health care system. There is an imperative need for new means of inhibiting the growth of S. aureus. As in many other organisms, iron is required for growth in S. aureus – an element that the bacteria must either extract or scavenge from within the human system. The majority of iron in the human body is found in heme, and many other organisms have evolved to utilize heme as an iron source. Recently, S. aureus was also shown to preferentially use heme-iron in early growth, but little is known about its heme uptake mechanism. Jason Grigg is exploring the function and structure of a set of four cell surface heme binding proteins found on S. aureus. By describing how the bacteria grows by extracting iron from its host, this research may lead to new ways to “starve” the bacteria and inhibit its pathogenesis.
The role of RyR2 in palmitate-induced beta-cell apoptosis in primary human and mouse pancreatic islets
Type 2 diabetes is a chronic disease affecting more than 2.2 million Canadians. The disease is characterized by the body’s inability to produce sufficient amounts of insulin — a hormone that regulates blood glucose levels. Over time, high levels of blood glucose can lead to complications like blindness, heart disease, stroke and kidney problems. Although the incidence of type 2 diabetes is increasing, its cause is still poorly understood. Type 2 diabetes results from a combination of beta-cell failure and insulin resistance. Obesity has long been known to be a major risk factor in the development of diabetes, and a leading hypothesis is that high saturated free fatty acids in the blood stream (hyperlipidemia) contribute to beta-cell death. Recent studies have also found that variations in certain genes, called “diabetes genes,” may increase susceptibility to the disease and play a role in beta-cell death. Kamila Gwiazda is investigating how these networks of diabetes susceptibility genes and acquired risk factors, such as hyperlipidemia, regulate beta-cell death and cause the onset and progression of type 2 diabetes. Gwiazda’s research could explain how obesity leads to diabetes and triggers other diseases that commonly occur in diabetics, ultimately leading to new therapies to prevent and treat the disease more effectively.