Cardiovascular complications are the major cause of morbidity and mortality in diabetes – a disease that affects millions of people worldwide. The lack of specific treatments for these complications is due, in part, to the poor understanding of the underlying cellular and molecular mechanisms, e.g., the signalling pathways that might cause malfunction, and pathways that protect normal vascular function. In diabetes, there are changes in the ability of blood vessels to constrict and relax, which in turn can affect blood flow and blood pressure. Prabhakara Nagareddy is studying how blood vessels function in diabetes and the mechanisms directly relevant to the development of vascular disease. He is exploring the vasoconstrictory role of a well-known growth receptor (epidermal growth factor receptor) pathway and the vasodilatory inducible nitric oxide synthase (iNOS) pathway in normal and diabetic arteries. By developing an understanding of how these pathways produce their effects, this research could facilitate the discovery of unique drug targets for future cardiovascular disease treatments, particularly for high blood pressure.
Year: 2006
The role of Annexin II in airway epithelial wound repair and the effect of corticosteroids on the Annexin II regulated pathway
Asthma is an inflammatory condition of the lungs that affects a growing number of individuals in developed countries worldwide. Current research and therapies for asthma are aimed at relieving the symptoms associated with the disease rather than the underlying defect. In spite of the use of anti-inflammatory agents, asthmatics experience progressive changes in airway structure and cumulative damage to the cells that line the airways (epithelium). The accumulation of damage due to ineffective repair may in part explain the airway’s hyperresponsiveness in asthma and highlights the importance of effective epithelial repair. Ben Patchell seeks to identify molecules that normally contribute to the process of epithelial repair and apply these findings to diseases such as asthma. Specifically, he is studying glycosylation, a process in which certain molecules gain sugars to become fully functional. Glycosylation has previously been shown to be essential in the repair of normal airway cells and there are demonstrated differences between the cells of normal and asthmatic individuals. Ben has developed a method to identify the unknown protein molecules responsible for these differences. Annexin II has been identified as a novel mediator of epithelial repair and has been demonstrated on the surface of airway epithelial cells. Ben is exploring how Annexin II and its associated proteins are regulated and the mechanisms by which they regulate cellular events such as migration in both normal and asthmatic epithelium. He is also investigating the effect of steroids, the primary therapy for asthma, on each of the cellular events. This research could lead to new research strategies and new therapeutics for asthma.
Alterations in hippocampus structure and function during pregnancy and motherhood. The role of corticosterone
Pregnancy and motherhood are life-changing events that often result in cognitive and mood disturbances. Research has shown decreased verbal recall and decreased spatial ability in women during the last trimester of pregnancy. Spatial memory relies in part on the integrity of the hippocampus in the brain, and on the steroid hormone corticosterone, but little is known about the effect of pregnancy and motherhood on these processes and how they relate to memory and learning. Jodi Pawluski is investigating the relationship between corticosterone, hippocampus structure and hippocampus-mediated learning and memory during pregnancy and motherhood. In addition to advancing understanding of how reproductive experience affects neurological, cognitive and hormonal processes in the mother, she hopes her work may contribute to the development of therapies for pregnancy-related diseases such as postpartum depression.
Evaluation of small molecule therapeutics modulating excitotocity in a mouse model of HD
Huntington’s disease (HD) is a progressive neurological disorder characterized by involuntary movements, emotional disturbances and memory loss. There is currently no cure for HD, and the disease is ultimately fatal. HD is caused by a selective loss of a population of nerve cells in specific regions of the brain, particularly the striatum. Accumulating evidence suggests that overactivation of glutamate receptors (transmembrane proteins involved in communication between nerve cells), which are abundant in the striatum, might lead to the selective death of nerve cells observed in HD. Mahmoud Pouladi’s research focuses on evaluating the efficacy of small molecule therapeutics known to target glutamate receptor signalling pathways in a model of HD. His work explores whether restoring physiologic levels of intracellular calcium by modulating glutamate signalling will prevent the neurodegeneration and associated motor and behavioural deficits observed in HD. This study will further our understanding of this disease and provide insights about glutamate signalling as a therapeutic target for the treatment of HD.
Aboriginal youth suicide and cultural continuity
Aboriginal youth in Canada have the highest suicide rate of any culturally distinct population in the world. In B.C., Aboriginal youth take their own lives twice as often as Aboriginal adults, and at a rate estimated at five to 20 times that of the non-native population. However, what these statistics fail to show is that rates of youth suicide vary dramatically across B.C.’s almost 200 Aboriginal bands. Ninety per cent of Aboriginal youth suicides occur in less than 10 per cent of the bands, and youth suicide is virtually unknown in a quarter of bands. Some Aboriginal communities are committed to their cultural past and invested in a shared future. For example, some Aboriginal bands have cultural facilities and a measure of communal control over health, education, policing and child welfare services. This cultural continuity has an impact on lowering suicide rates. Travis Proulx is investigating whether community efforts to teach Aboriginal youth their native language also predict future wellbeing. If young people who are competent in their native language are less likely to commit suicide or be involved in serious accidents, band councils and governments can use this information to design programs that build Aboriginal youth resilience and help prevent suicide.
Molecular epidemiology of Giardia lamblia in British Columbia’s drinking water supplies
Giardia lamblia is a waterborne parasite that causes giardiasis, a diarrheal disease commonly called ""beaver fever”. Despite the comprehensive water quality management measures in B.C., this parasite is often detected in surface water supplies and is the second leading cause of gastrointestinal illness in the province. While current surveillance methods for G.lamblia in water supplies allows for enumeration of the parasite in water, the test cannot differentiate between infectious and non-infectious strains. Natalie Prystajecky is examining a library of archived water samples collected across B.C. over 13 years to determine if the strains in B.C. surface water are infectious to humans and how frequently, what the sources are, and where these strains are found. She is also assessing the effectiveness of control measures such as watershed protection and agricultural waste management best practices in protecting water quality. This information could lead to more effective environmental and health policies and public health interventions.
A population health-based approach to nurse human resource planning in BC
Health human resource planning is identified repeatedly as the foremost priority in the field of health services research. Current approaches to health human resource planning include the need to move beyond “head counts” of health care providers to more robust and dynamic approaches that include consideration of many different factors. Improved planning for the registered nurse workforce is of particular concern, requiring an understanding of the influence of contextual issues such as the impact of population health trends, changing demographics and policy directions on human resources planning initiatives. Sandra Regan’s research is focused on identifying the numbers and characteristics (education, competencies, employment patterns and roles) of the registered nurses needed to meet the health care needs of British Columbians. In order to determine the numbers and characteristics of registered nurses required in BC, her research will combine existing registered nurse databases with population health data, interview data and focus group data from key players in the health care system including consumers. This research will assist decision-makers such as government, employers and educational institutions to understand the implications for future planning of health care services provided by registered nurses. It will also contribute to understanding how to better plan for other health care providers (e.g. pharmacists, physicians).
Epigenetic Regulation of Natural Killer Cell Receptor Genes
The innate immune system, unlike the adaptive immune system, does not first require exposure to a foreign substance before immunity can be developed. Natural killer (NK) cells—a subset of white blood cells—make up a major part of the innate immune system. NK cells are considered a first line of defence in the body as they can recognize and destroy cells that have been altered, such as in the case of virus-infected or tumour cells and also foreign cells. This recognition is through the interaction of receptors on the surface of NK cells, with the receptor molecules called MHC class-1, expressed on the surface of target cells. The absence or alteration of numbers of MHC class-1 on abnormal target cells results in their destruction by NK cells. In both humans and mice, there is great variability in the number and combination of receptors on individual NK cells. Furthermore, it has recently become evident that the receptor repertoire of NK cells can change in response to various stimuli. Building on her previous MSFHR-funded work, Arefeh Rouhi is studying the mechanisms that control these variations among NK cells. Understanding how NK receptors are controlled is critical to the interpretation of how the repertoire is modified in response to infection and tumour cells, and the response of NK cells to mismatched bone-marrow grafts. Ultimately, this knowledge may lead to the development of methods to use the body’s own immune system to protect against infections and malignancy.
Cluster Analysis for High-Dimensionality Population Health Data
Population health research seeks to develop a better understanding of how social, cultural, environmental, occupational and economic factors determine health status. While most population health research focuses on specific hypotheses, understanding the bigger picture can yield insights on a larger scale. How socio-economic factors influence or correlate with health status, how diseases group together in constellations, and how these relate to health services usage, medication usage and health-driven outcomes are all important questions. Cluster analysis (CA) is a class of statistical techniques that can be applied to data that exhibit natural patterns. However, current CA methods are poorly suited to broad population health data, which may contain hundreds of variables with many dimensions. The result is that patterns between classes of variables can be lost in the statistical “noise.” Eric Sayre is developing a new method of CA called Cluster Analysis for High-Dimensionality Data (CAHDD), which provides a means for filtering statistical noise, and allowing important patterns to emerge from the data. By applying CAHDD to Canadian population health data, Eric’s research seeks to answer big-picture questions about socio-economic factors and health status. CAHDD will be available for other health researchers to interpret population health data, leading to significant advances in our understanding of the determinants of health status in our population.
Antagonism of the p75 Neurotrophin Receptor promotes neurotrophin-mediated neural regeneration and plasticity within the injured spinal cord
Functional recovery following spinal cord injury is extremely limited, leaving individuals with limited mobility, autonomic dysfunction, and chronic pain. The lack of significant recovery following this type of injury reflects the failure of mature nerve fibres (axons) to regenerate and the incapacity of uninjured nerves to undergo compensatory growth (plasticity). Regeneration and plasticity are governed by a balance between growth-promoting and growth-prohibiting factors within the injured spinal cord. Neurotrophic factors and myelin-associated inhibitory proteins (MAlPs) both influence axonal growth through axonal receptor complexes that include the p75 neurotrophin receptor (p75NTR). MAIPs suppress axonal growth through p75NTR; neurotrophic factors augment axonal growth partly by inhibiting p75NTR. Angela Scott has found in past research that both the regeneration of injured axons and the plasticity of spared axons can be improved with the antagonism of p75NTR. Her current research explores the role of p75NTR following spinal cord injury. By determining the functional significance and clinical relevance of p75NTR antagonism, her work may lead to clinically relevant therapeutic treatments that improve functional recovery for people with spinal cord injuries.