Marco Gallo is using Caenorhabditis elegans (a small worm) as a model organism to determine how mitochondrial 2-oxoglutarate carrier (OGC) affects aging and insulin signalling. He is studying how this protein interacts with the insulin pathway, and how it affects the development and function of mitochondria, which serve as the cell’s energy source. The proposed mechanism by which OGC is involved in the occurrence of diabetes is by modulating insulin signalling (the cascade of molecular events that result in insulin production). A related version of this protein (B0432.4) is also found in C. elegans. In worms, suppression of this protein resulted in a 20 per cent increase in their average and maximum life-span & in changes in the levels of insulin secretion. Gallo’s research aims to identify the mechanisms that mediate the interaction between OGC and insulin signalling. He is addressing this question with work on C. elegans, mouse & human cell lines. This work could shed more light on the changes that occur in the mitochondria and lead to metabolic diseases, with an emphasis on diabetes.
Research Location: University of British Columbia - Point Grey
Expiratory flow limitation, dynamic hyperinflation and respiratory muscle fatigue during exercise in men and women
The act of breathing is a complex physiological process involving the interaction of numerous respiratory muscles and a neural control network. These respiratory muscles are the only skeletal muscles in the body whose functioning is necessary to sustain human life, making their ability to resist fatigue very important. Despite this, research has shown that high intensity exercise can induce respiratory muscle fatigue. Given the life-sustaining role of the respiratory muscles, it is important to understand the mechanisms of fatigue, how it is best detected, and how the human body responds and adapts to fatigue. Also, research suggests that physiological and anatomical differences may make women more susceptible to respiratory muscle fatigue compared to men. However, there are no studies that have systematically examined sex-based differences in respiratory muscle fatigue, and the “normal” pulmonary response to exercise in women is not well understood. Jordan Guenette was previously funded by MSFHR for his early PhD work identifying the respiratory limitations women face as they age. Now, he is examining the mechanisms and consequences of respiratory muscle fatigue in men and women during whole body exercise. His study will determine if the smaller lungs and airways in women cause greater respiratory muscle fatigue compared to men. He will also investigate whether high levels of respiratory muscle work reduce blood flow to other parts of the body and are responsible for impairment of whole body exercise performance. Guenette’s project will address questions significant to both basic and clinical science, outlining how men and women differ with respect to the normal pulmonary physiology of exercise. His findings have the potential to influence exercise rehabilitation programs for a variety of patient populations, and exercise prescription to prevent disease in healthy individuals.
Metacognitive factors in smoking: causal effects of maladaptive appraisals of cravings, thought suppression and nicotine withdrawal on craving severity
Cigarette smoking is directly responsible for the deaths of more than 45,000 Canadians each year. Although the majority of current smokers want to quit, smoking cessation can be extremely difficult. Since smokers are more likely to lapse after experiencing intense, persistent and distressing cravings, identifying factors that influence the severity of smoking-related thoughts, images and impulses is critical for understanding and preventing cessation relapse. Recent theories on the role of metacognitive processes in psychopathology hold promise for increasing our understanding of this important health issue. Metacognition refers to how people think about and react to unwanted thoughts and impulses. In her Master’s level research, Elizabeth found that among individuals attempting to quit smoking, metacognition is associated with nicotine craving severity and smoking cessation difficulty. Specifically, smokers who viewed their cravings as more important to control and more personally meaningful experienced more frequent, distressing and persistent cravings and were more likely to relapse one month later. Elizabeth is now building on this research, investigating the causal factors that contribute to personally meaningful interpretations of cravings, in relation to the effects of acute nicotine withdrawal and efforts to control thoughts about smoking. The results of Elizabeth’s research will help build understanding of the psychological factors that increase the risk for smoking relapse. They may also lead to innovative clinical strategies focused on appraisals and responses to cravings.
Logic, intuition and delusions: dual stream processing biases in decision-making
Delusions, a key characteristic of schizophrenia, are fixed false beliefs that are firmly held despite convincing evidence to the contrary. An underlying mechanism that can account for this debilitating symptom remains elusive. “Dual-stream information processing” is a decision-making model that divides reasoning into two separate components: a fast, intuitive stream, and a slower, logical stream, similar to our understanding of decisions made by the “”heart”” or “”gut”” versus those made by the “”head””. For most decisions, intuition and logical reasoning converge onto the same conclusion. However, in instances where intuition and reason do not agree, there may be processing differences between healthy people and people with schizophrenia. Healthy people show a bias toward the logical stream, prompting them to more carefully examine the available evidence. In schizophrenia, individuals may not detect conflict between the two streams and may not have a bias toward the logical conclusion. This could enable their erroneous intuitive interpretations of events to endure unchallenged, leading to delusions. William Speechley is testing this hypothesis by studying how people make sense of conflicts between the intuitive and logical streams of reasoning. Healthy individuals and delusional schizophrenia patients will be given reasoning tasks and their brain activity will be recorded using functional magnetic resonance imaging (fMRI). He predicts that healthy controls and delusional schizophrenia patients will differ when the two streams of reasoning conflict, and that the patient group will not adequately recruit logical reasoning areas of the brain during conflict. He also expects that fMRI will indicate greater activity in areas relating to intuitive processing among schizophrenics. This research will make a significant contribution to our understanding of the cognitive basis for the formation and maintenance of delusions in schizophrenia, potentially leading to more effective treatment strategies.
Ambient air pollution, residential traffic noise, and cardiovascular disease in British Columbia
Cardiovascular disease is the leading cause of death worldwide and accounts for approximately one-third of deaths across BC and Canada. Growing evidence has shown that air pollution and residential traffic noise are associated with cardiovascular disease. Chronic exposure to air pollution may induce and accelerate atherosclerosis, and environmental noise pollution is associated with hypertension. Previous studies have not clarified the independent effects of noise exposure and the joint effects of both ambient air pollution and residential traffic noise on the risk of cardiovascular events. Wenqi Gan is investigating if British Columbians exposed to higher levels of air pollution and residential traffic noise have an increased risk of cardiovascular events such as heart attacks, and whether this effect is greater among older age groups and individuals with other existing health conditions. Using air quality monitoring data , calculated environmental noise levels, as well as cardiovascularhospitalization and death records in Metro Vancouver, his study will follow more than half a million residents aged 45-85 over five years. Advanced statistical methods will be used to analyze the relationship between air pollution and noise exposure levels and the risk of cardiovascular events. Gan’s study will help identify the impacts of multiple environmental exposures on the risk of cardiovascular events and will also provide important evidence to support environmental policy making about air pollution, urban design, and transportation planning.
Combined analyses of the environmental risk factors for Lung Cancer in British Columbia and the resulting burden from particulate air pollution, arsenic and radon exposures
Every year, approximately 2,200 British Columbians die of lung cancer and an additional 2,700 are diagnosed with the disease. While tobacco smoke is the primary cause of lung cancer in BC, approximately 25 per cent of lung cancer cases are not attributable to smoking. In fact, lung cancer in non-smokers accounts for the seventh leading cause of cancer death. Studies have found that environmental factors increase the risk of lung cancer in both smokers and non-smokers, including exposure to particulate air pollution, residential radon (a radioactive gas that leeches from soil and building materials), and arsenic in drinking water. These three exposures are widespread throughout BC and affect a large percentage of the population. However, no study has been conducted that determines how many, where and to what levels the BC population is exposed to these environmental carcinogens, or the risks posed to lung cancer development and the resulting burden on lung cancer in BC. Perry Hystad is creating current and historical provincial exposure models for particulate air pollution, radon and arsenic. These results are linked with provincial lung cancer data collected by the National Enhanced Cancer Surveillance System. His research will include exposure assessment, epidemiological analysis and burden of disease calculations. Hystad’s findings will shed light on the risks posed by these environmental carcinogens across BC. Ultimately, this work could help identify potentially susceptible populations and contribute to the development of prevention measures.
Evaluating changes in the social, sexual, and drug-using networks of men who have sex with men (MSM) following testing and an enhanced prevention intervention for acute HIV infection: Applying social …
The primary purpose of this research is to provide insight into how to reduce the rising rate of HIV infection among men who have sex with men (MSM) in Canada. The number of HIV infections in Canada continues to rise annually, with MSM accounting for a disproportionate number of these new infections. Evidence now suggests that individuals are highly infectious during the early stage of HIV infection, and these individuals are responsible for generating 11 to 40% of new infections annually. Indentifying individuals as soon as possible after acquiring HIV infection and providing a risk reduction intervention is necessary to curtail this HIV epidemic among MSM. Traditional HIV antibody testing is unable to detect HIV during this early infective stage; a new technology (nucleic acid amplification test-NAAT) that can identify early HIV infection has recently become available and will be used in this study. Traditional epidemiologic methods have focused on individual-level risk factors (e.g. number of sexual partners, condom use) but these have failed to fully explain transmission dynamics or control epidemic growth. Social network analysis (SNA) is a methodology that considers relationships, and interactions among those with varying risk characteristics in the social context. SNA is increasingly being applied to infectious disease epidemiology and research suggests this is a useful approach to the study of HIV transmission dynamics. MSM who acquire HIV are likely to belong to social, sexual, and drug-using networks whose members have similar risk behaviours. We hypothesize that early HIV detection and risk reduction interventions targeting these individuals, and their networks, will reduce the transmission of HIV. This research will employ SNA to examine and describe the social, sexual, and drug-using networks of MSM diagnosed with early HIV infection using NAAT. Network information will be used to identify networks containing high levels of risk behaviour and networks with a high incidence of early HIV infection. An enhanced prevention intervention will be developed with MSM community participation and implemented among individuals within the network who are engaging in high risk behaviour, and who are prominent in the network. In addition, SNA will be used to evaluate how the networks change over time (post-intervention) considering network structure, sexual mixing patterns, rate of partner change, risk behaviour, and to determine forward HIV transmission events.
Community Learning Centres: A Model of Community Engagement in Health, Education & Training
There are disproportionately high rates of poor health among First Nations populations in comparison to the general Canadian population. A contributing factor is the limited access many geographically-isolated rural and remote First Nations communities have to health information. Dr. Sandra Jarvis-Selinger is focusing on a new and innovative approach supporting community access to health information. This approach involves the formation of Community Learning Centres (CLCs) in four communities located in the Ktunaxa Nation in southeastern BC. A CLC is both a physical and a virtual space for community members to access Internet-linked computers and web-based resources developed according to community-defined health priorities. Health information is created by and for community members and is both accessed at and disseminated via CLCs through information and communication technologies. Community engagement is the cornerstone of this project, with due emphasis placed on community input and governance, local health priorities and inclusion of traditional medicine, language and knowledge. Dr. Jarvis-Selinger is conducting a program evaluation to determine the effectiveness and sustainability of the CLC design and implementation. The evaluation is being co-developed with each community in order to match the communities’ needs, workflow, schedule and style of participation. This research will increase our understanding of how to successfully and sustainably: 1) support community-university partnerships; 2) improve community wellness; 3) expand access to and awareness of community health resources; and 4) increase employment opportunities through technical, research and interpersonal skills training. Overall, this research promises to make a meaningful contribution to the domain of First Nations community health through the use of technology.
Regulation of T Cell Development, Function and Transformation by Interleukin-7.
Immune disorders – such as immunodeficiencies, leukemia and lymphoma, autoimmunity, and allergy – are significant health problems. For example, every year 5,600 Canadians people die of cancers of the immune system, such as leukemia and lymphoma, and these cancers account for 42% of all cancers in children. Current treatments for these cancers, such as chemotherapy and radiation therapy, have significant shortcomings. To improve recovery rates and reduce unwanted side effects, researchers need to develop new, specifically targeted treatment approaches. Treating diseases with few side effects requires knowing the signals involved in disease development. Dr. Ninan Abraham is focusing his research on understanding how a cytokine called interleukin-7 (IL-7) regulates immune cells by interacting with proteins to trigger biochemical pathways that control normal cell development and function. IL-7 is an essential growth factor that promotes the development of T cells and memory T cells, which are both essential for the body’s response to pathogens that lead to disease or infection. Being able to enhance development or survival of T cells by manipulating IL-7 could lead to the creation of more effective vaccines to boost the body’s immune response to disease. Conversely, since over-expression of IL-7 is associated with several forms of human T cell lymphoma, being able to limit this cytokine’s activity could also be important. By identifying how IL-7 promotes the development or survival of T cells and memory T cells, Abraham hopes for new strategies for treating these cancers and enhancing vaccines for long-term immunity.
Pharmaceutical sales representatives, patient safety and cost-effectiveness of care: comparative cross-sectional survey
Prescription medicines are a common and important form of treatment offered by family doctors. The information that doctors receive about the effectiveness and safety of medicines helps to determine their prescribing choices. Most doctors in Canada see pharmaceutical sales representatives regularly. Previous research has demonstrated that sales representatives influence prescribing choices and that doctors often underestimate the extent to which they are influenced. A recent example of this influence emerged in the US with the arthritis drug Vioxx. Despite a 2001 Food and Drug Administration advisory committee recommendation that doctors be warned of heart attack risks associated with the drug, sales staff were advised not to inform doctors of. By the time Vioxx was withdrawn from the market in 2004, it had been linked to between 88,000 and 140,000 heart attacks. Dr. Barbara Mintzes is investigating whether information critical to safe prescribing is provided to doctors by sales representatives. She is gathering data from three countries: Canada (British Columbia and Quebec), the US, and France. She aims to identify best practices in regulation of drug promotion, and to understand how the messages doctors receive from sales representatives can be incorporated into education to improve prescribing. Ultimately, her goal is to improve prescribing safety and appropriateness. A key component of the research will be discussions of the implications of the results with policy-makers, physicians, medical educators and industry.