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).
Research Location: University of British Columbia - Point Grey
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.
Exposure to polybrominated diphenyl ether (PBDE) flame retardants and thyroid effects in pregnant women
Polybrominated diphenyl ethers (PBDEs) are chemical flame retardants used in furniture foams, certain textiles and many plastics. In Vancouver, PBDE levels in human breast milk increased by about 15 fold from 1992 to 2002, bringing current levels to among the highest reported in the world. While the human health effects from ambient PBDE exposure are unknown, animal and laboratory studies indicate that PBDEs alter the levels and transport of thyroid hormones. This is of particular concern during pregnancy, when thyroid hormones play a critical role in fetal brain development. Because even small changes in maternal thyroid hormone levels in early pregnancy have been linked to neurological deficits in children, the thyroid disrupting potential of PBDEs is of interest for public health. Glenys Webster’s study is examining the relationships between PBDEs and thyroid hormones in 150 pregnant women in Vancouver. Using blood tests, her work will determine whether PDBEs are associated with altered thyroid hormone levels at different stages of pregnancy. A detailed questionnaire will also be used to identify the main sources of maternal exposure to PBDEs. Ultimately, Glenys’ research may lay the foundation for future investigations of PBDEs, other environmental toxins and neurological development in children in Vancouver.
Antibiotic Resistance in Superbugs: Regulation of the Blar beta-lactam sensor of MRSA and the MexAB-OprM multidrug-efflux effector PA3719 from Pseudomonas aeruginosa
Every year, Canada spends hundreds of millions of dollars in the fight against antibiotic-resistant “superbugs”, bacteria that have evolved to outmaneuver the drugs that are designed to kill them. The elaborate resistance machinery that bacteria have developed can be energy consuming for the organism to construct and maintain, so bacteria will activate this defense system only in the presence of antibiotics. This effect is seen within superbugs that are resistant to beta-lactam antibiotics such as penicillin. Mark Wilke is working to understand the regulatory machinery bacteria use to switch on beta-lactam resistance, specifically within the notorious superbugs MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa. He is using a technique called X-ray crystallography, which generates atomic resolution “snapshots” of proteins and other molecules in action. His findings could lead to new strategies for combating superbug infections.
Novel redox-elimination mechanism of enzymatic glycoside hydrolysis: A detailed study of Family 4 glycosidases
Carbohydrates are found in every facet of life, not only in metabolic pathways, but also as key mediators in intercellular communication and cellular activity. Associated with these important biomolecules are a class of enzymes—glycosidases—that contribute to the breakdown of carbohydrates, allowing for their use as an energy source by the cell. Interruption of these processes can affect cell growth by limiting the supply of available nutrients. With more than 90 different known glycosidase families, the recently-discovered Family 4 glycosidases have been shown to operate through a different mechanism. In addition, this family exists in a number of bacteria, but not in mammals. Continuing in research that was previously funded by MSFHR, Vivian Yip is performing a detailed investigation of the mechanisms of Family 4 glycosidases. Ultimately, she is interested in exploring how inhibition of these glycosidases could be used to develop antibiotics that selectively compromise bacteria, but not the host.
Coping with Rheumatoid Arthritis: The Effect of Psychosocial Factors on Chronic Pain
Rheumatoid arthritis (RA) is an incurable disease that affects approximately 1 per cent of the western population. It is associated with a variety of symptoms including chronic pain, stiffness and inflammation of joints, fatigue, and frequent mood changes. Because there is no cure, treatment focuses on alleviating symptoms and maintaining mobility and function. Disease factors only partially predict pain and disability among RA patients; consequently, there is growing interest in the influence of psychological and social factors on the progression of this disease. Amy Zwicker is examining the role and degree to which social support from friends and family, and effective coping strategies may help to decrease pain and increase functional ability in people living with RA. She is also examining the effects of these psychosocial factors on mood and physical well-being of patients and their spouses. Findings from her research may contribute to the development psychologically-based interventions that help RA patients deal more effectively with the pain and disability associated with the disease.
Molecular basis of tenascin elasticity and mechanotransduction
Tenascin is an important family of proteins found in the extracellular matrix of tissues—the filamentous structure that is attached to the outer cell surface and provides anchorage, traction, and positional recognition to the cell, and plays important roles in regulating the interactions between cells and the extracellular matrix. It is also known that tenascin mutations are linked to disorders that affect the mechanical properties of skin tissues and joints. However, little is known about the mechanical properties of tenascins and how they are regulated to adapt tissues to withstand force. To study tenascin, Dr. Hongbin Li is stretching single molecules of the protein and examining its mechanical response. He will also evaluate the consequences of disease-causing mutations on the mechanical behaviour of tenascins. These studies will provide new insight into the molecular basis of tenascin mechanics, and help to pinpoint the cause of tenascin-related connective disorders. They may also offer useful information in developing tissue engineering strategies for skeletal repair.
Endoplasmic reticulum-plasma membrane contact sites: Regulation of ER structure and cell growth
Lipids play important roles in all cells, separating the cell from the outside environment and serving to divide the cell into distinct compartments called organelles. In order to carry out their critical biological processes, organelles need to contact and communicate with each other. The disruption of these contacts can result in defective movement of lipids, and the accumulation of lipids is a factor in diseases such as atherosclerosis, Alzheimer’s disease, type 2 diabetes and motorneuron diseases. The endoplasmic reticulum is an organelle that is made up of a network of membranes within cells, involved in the synthesis, modification, and transport of cellular materials. Communication of the endoplasmic reticulum with other organelles is especially important to the cell, because it is the site of many metabolic activities, including making lipids and proteins. Dr. Christopher Loewen is working to determine how the endoplasmic reticulum contacts and communicates with other cell compartments, particularly with regards to lipid synthesis. By studying these contacts, he hopes to shed light on both normal and dysfunctional communication, potentially uncovering new ways to fight lipid accumulation.
Characterization of the influence of covalent histone modifications on DNA methylation in mammalian cells using a novel genomic targeting system
Normally, cells in the body grow, divide, and die in an orderly manner, under the direction of their DNA, the genetic blueprint of life. However, damage to the DNA in a single cell can disrupt this regulated process, prompting the cell to begin dividing uncontrollably and becoming cancerous. A subset of cell growth regulating proteins – those encoded by the tumour suppressor genes – normally act to inhibit cell growth. In many cancer cells, these proteins are no longer produced, not because the genes that encode them have become mutated, but because they have been shut off, or “silenced”. Gene silencing frequently involves methylation, a specific chemical change in the genes’ DNA. However, the cause of methylation and its associated gene silencing cascades remain unclear. Dr. Lorincz is determining the underlying cause of DNA methylation, using a novel mouse cell model system that he has developed. The knowledge gained from this work may lead to the development of pharmaceuticals that inhibit DNA methylation and, in turn, provide new agents for the treatment of those cancers arising from aberrant methylation of tumour suppressor genes.
Methods and tools for integrative meta-analysis of neuroscience micro array data
Dozens of neuroscience laboratories around the world are using gene expression microarrays, a technology that simultaneously monitors the activities of thousands of genes in a sample of brain tissue or cells. While the specific goals of each study may vary, a common theme is increasing our understanding what happens to the brain when it is diseased (as in Alzheimer’s disease or schizophrenia) or damaged by injury (such as stroke). These studies each generate huge amounts of data, with the potential for new discoveries arising from the compilation and comparison of results across laboratories. However, there have been few efforts to date to provide advanced analytic capabilities that can span data sets, and none that address the specific needs of neuroscience. Dr. Paul Pavlidis is developing methods, databases and software to gather, integrate and compare the vast amount of data compiled from neuroscience-related gene expression data. The tools he is developing will allow brain researchers to submit their own data, compare it to published data or that of their collaborators, and combine microarray data with other types of gene expression data. This work will help researchers share data and collaborate in studies that target diseases of brain function.