Vesicle transport is a process that underlies various molecular events, such as the movement of glucose transporters in response to insulin in muscle and fat cells. Malfunctions in these transport processes can result in a range of problems, including diabetes or problems in learning and memory formation. An important but unclear aspect of vesicle transport is how molecules are retained within specialized compartments in the cell and how they are released to the cell surface. Chris Tam’s research goal is to identify proteins that control the storage and release of molecules in yeast cells. She is doing this by conducting high-throughput genome-wide screening to uncover yeast genes that are required for the intracellular storage of the protein Chs3. As the basic cellular mechanisms that regulate vesicle transport are likely conserved in both yeast and humans, this understanding from yeast cells may provide insights into various fundamental aspects of human biology. Ultimately, this work may contribute to the development of new treatments for diabetes and diseases involving memory and learning deficits.
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Peptide YY Therapy for Obesity
Obesity is a debilitating disease reaching pandemic proportions in developed countries. Several hormones are involved in regulating feeding and energy, including peptide YY (PYY), an appetite regulatory hormone. PYY is released from the gut in response to a meal, relaying signals to the brain to prevent further eating. Several research studies, including work by Suraj Unniappan, have shown that PYY causes inhibition of feeding when administered at pharmacological doses in experimental models. However, the body very rapidly clears PYY from the system, and continuous delivery of PYY results in desensitization against the peptide. This prevents prolonged and consistent effects of PYY on feeding and weight loss. Suraj’s preliminary results indicate that a fat cell-derived hormone, leptin, enhances and prolongs the appetite regulating effects of PYY. In this research, he is working to develop a combination therapy for obesity using PYY and leptin. Next, he proposes to develop a cell-based therapy for obesity using cells that, when activated by a drug, will synthesize PYY and release it in a meal-responsive manner. If this research is found to be effective in reducing food intake and promoting weight loss, it could be beneficial for treating obesity and its debilitating complications.
Stimulus-driven control in visual neglect: the role of awareness
A person’s field of vision, or visual field, includes an enormous amount of information. By means of attention and eye movements, people are able to select certain objects and location from any point in the visual field. Selection may be stimulus-driven (the properties of the object attract a person’s attention involuntarily, such as a flashing light) or goal-driven (the observer purposely turns their attention to an object). People with damage to the right parietal or parieto-temporal lobes of the brain—commonly brought on by stroke, vascular, demyelinating or infectious diseases—suffer from visual neglect, limiting their ability to select information from the visual field. They often fail to notice items in the visual field opposite to the damaged area of their brain. Interestingly, research has suggested that visual neglect in these people is a function of goal-driven selection, and that stimulus-driven selection function may remain intact. Wieske van Zoest’s research is investigating the role of stimulus-driven control in patients with visual neglect. While participants—patients and healthy controls alike—may not be aware of stimulus-driven influences in selection, direct measures (such as eye movement recording) allow for investigation of the contribution of stimulus-driven control. The proposed work may have significant practical relevance for patients, allowing them to process information if it is presented in such a way that it draws attention automatically in a stimulus-driven fashion.
Cardiovascular morbidity and mortality associated with the use of corticosteroids in patients with rheumatoid arthritis: a population based study
More than 300,000 Canadians have rheumatoid arthritis (RA), a disease that causes chronic pain and inflammation in the joints. In British Columbia, more than half of people with rheumatoid arthritis receive corticosteroids to reduce inflammation. Several studies have shown that patients with RA are more likely to develop and die from cardiovascular disease (CVD) and, on average, live 12 years less than people without RA. The increased risk for CVD cannot be fully explained by traditional risk factors such as smoking, high blood pressure, diabetes, high cholesterol and a family history of CVD. Disease severity as well as treatment used in the management of the disease seems to play an important role in the development of CVD. Dr. Antonio Aviña-Zubieta is studying cases of individuals in BC who were diagnosed with RA between 1997 and 2000, and evaluating outcomes in people who received corticosteroids with those who did not to determine if there are differences between the two groups in the number of heart attacks, heart failure and stroke. This will help to establish if corticosteroids used in the treatment of rheumatoid arthritis contribute to CVD. He also will study whether the brand, dose and duration of use with different drugs influence the risk of heart disease. The results could offer new insights, leading to improved treatment and management of rheumatoid arthritis and other conditions for which these drugs are commonly prescribed.
Particulate Matter Air Pollution Induces Vascular Endothelial Dysfunction
Despite improvements in air quality over the past few decades, research shows that elevated levels of particulate matter air pollution (called PM10) are associated with an increase in cardiovascular disease (CVD) and death. More than 800,000 deaths a year can be attributed to PM10-induced CVD, including life threatening irregular heartbeats, atherosclerosis, heart attack and stroke. Diesel exhaust particulates are the major contributor to PM10 in most urban centres worldwide. But there is little evidence to describe how these particulates affect cardiovascular function. The endothelium is a monolayer of cells separating blood from the vascular wall, thus providing physical and biological protection. Importantly, endothelium plays a major role in protecting, activating and controlling cardiovascular function. Activation of endothelium is implicated in the development of atherosclerosis. Ni (Nicola) Bai is investigating whether exposure to diesel exhaust particulates induces dysfunction in these cells, causing the progression of atherosclerosis, and ultimately leading to heart attack and stroke. The findings should help develop interventions that minimize or prevent deaths associated with breathing polluted air.
Healing Practices of Azorean Immigrants: Implications for Practitioners in North America
Therapists in BC need to develop culturally sensitive mental health services to reflect the changing demographics of BC’s population and better serve immigrant clients. This is especially important because research has shown that immigrants simultaneously use traditional healers from their country of origin and local health care services to alleviate symptoms of illness. More than 30,000 BC residents report Portuguese origins. Birdie Bezanson is studying the beliefs, values and methods of traditional Portuguese healers in BC and the Azores Islands in Portugal, and the implications for local practitioners in multicultural counselling. Clinical practices and healing processes develop within and reflect particular cultures and value systems. Birdie is examining the interface between traditional and clinical methods of dealing with distress to develop a more comprehensive understanding of healing and well-being. This research is directed at informing the development of culturally sensitive treatment alternatives that will enable local practitioners to accommodate the needs of Portuguese clients and other immigrant communities in the province.
Characterizing looking behaviours within social scenes: Implications for a social deficit in autism
Autism Spectrum Disorder (ASD) encompasses five neurological disorders that change how the brain processes information. Children and adults with ASD have varying levels of difficulty with social interaction and communication, may exhibit repetitive behaviours, and may have unusual attachments to objects or routines. One form of ASD – classic autism – is the most common neurological disorder affecting children, and usually appears in the first three years of a child’s life. Elina Birmingham is studying the deficiencies that limit the ability of people with ASD to interpret social cues and develop and maintain social interactions. She wants to determine whether these deficits reflect a perceptual inability to process people’s faces (the eyes and mouth, for instance), or a failure to understand and interpret the social cues that are part of social interactions. To do this, she is tracking eye movements to determine how people with ASD respond to social scenes of people interacting and non-social scenes with no interaction. The results should help confirm whether people with autism have the greatest difficulty interpreting social interactions, information that can be used to develop diagnostic and rehabilitation techniques.
Genetic discrimination in mutation carriers identified through predictive testing for HD
In her earlier research supported by a MSFHR-BCMSF Junior Graduate Studentship Trainee Award, Yvonne Bombard completed a qualitative study of how individuals live with, and manage the potential for, genetic discrimination. Based on these findings, she adapted an Australian survey to reflect the concerns and experiences relevant to Canadians at risk for Huntington’s disease (HD). Yvonne’s work now focuses on recruiting 300 Canadian participants to complete the adapted survey. Survey results will then be analyzed to identify the nature and frequency of discrimination against Canadians who test positive for the HD gene mutation (but who have not yet developed outward symptoms) when applying for insurance, in their work environment, and in social and family settings. The findings of the study will help counsellors, patient support groups, and the health policy communities identify areas where more education or policy may be needed. Ultimately, this research may lead to better supports and improved health of individuals identified as being at risk for developing Huntington’s disease.
Investigation of the role Cnk2p plays in ciliary length control
Eukaryotic cilia are membrane-bound organelles in cells known for their function to propel cells (such as sperm cells), or move fluid over a cellular surface (such as respiratory epithelial cells in the lungs). More recently, researchers have looked more closely at immotile (unmoving) primary cilia which are found on almost all terminally differentiated mammalian cells (mature cells that no longer grow). Previously believed to have no function, immotile primary cilia have now been shown to have significant signalling roles and are gaining recognition as sensory organelles. A series of recent discoveries has pointed to the idea that the cilia found in tubular epithelial cells of the kidneys are required for maintaining the differentiation of kidney tubules, and that the loss of this function results in Polycystic Kidney Disease, a common human genetic disease also found in other species. Focusing on one member of a family of proteins known as the NIMA-related kinases, Brian Bradley is studying the connections between cilia, the processes by which they are assembled, and cell division. He hopes his work can lead to a better understanding of the role of cilia in human health and disease.
Tissue Specific Functions of ABCA1
An individual’s cholesterol levels – both LDL (or “bad” cholesterol) and HDL (or “good” cholesterol) – are known to be a significant predictor of the risk for heart disease. While much attention has been focused on lowering levels of LDL, much less is known about the factors that determine HDL levels and how to alter these levels. However, research suggests that every 1 per cent increase in HDL levels results in an approximately 2-3 per cent decrease in risk for cardiovascular disease. With insight into how to raise HDL levels, a majority of the population might avoid developing heart disease. The gene ABCA1 has been identified as crucial to the production of HDL cholesterol, and is expressed in many tissues in the body. However, it is unclear which specific cell types or organs are responsible for the generation of HDL particles. Liam Brunham is investigating the specific role of ABCA1 in different tissues of the body and determining how ABCA1 in these tissues responds to different genetic and dietary environments. This research will increase the understanding of how ABCA1 functions to determine HDL levels, and suggest new ways to protect against heart disease.