The hypothalamic-pituitary-adrenal (HPA) axis is a brain-hormone system that plays an important role in the body’s reaction to stress. The HPA axis controls the secretion of glucocorticoids – steroid hormones that are released from the adrenal glands during stressful episodes. In the short term, acute elevations in circulating glucocorticoids are beneficial, serving to meet the metabolic demands of stress by mobilizing energy stores. In the long term, however, chronic stress-induced elevations in glucocorticoids are implicated in several forms of systemic, neurodegenerative and affective disorders, including depression. Dr. Viau is working to determine the sites and mechanisms by which testosterone acts in the brain to regulate the HPA axis. Given the association of chronic stress with depression and the potency by which testosterone inhibits stress-HPA function, Dr. Viau is investigating where stress, testosterone, and depression intersect in the brain. Dr. Viau hopes his discoveries will be taken from the bench to the bedside, towards implementing sex steroid replacement as an adjunct to antidepressant therapy.
Research Location: University of British Columbia
Development and regulation of individual mammalian CNS synapses
A single central neuron can receive signals from up to 50,000 other neurons, which each connect to the central neuron across a synaptic junction. Dr. Timothy Murphy studies individual synapses in the mammalian central nervous system to determine how each contact develops and is regulated. The development and functioning of these individual connections are believed to be building blocks in creating and strengthening the neuronal networks for learning and memory. Dr. Murphy and his colleagues are investigating a number of aspects related to individual synapses. They include: the mechanisms that control the strength of synaptic transmissions at single contacts; the role of calcium in synapse development; the mechanisms that prevent excess calcium from flowing into neurons; and how different types of calcium channels in neurons react to specific and complex patterns of electrical signals in the brain. These basic insights into the behaviour of central nervous system synapses will be important for future diagnostics, as well as therapeutics for diseases of the central nervous system. For example, alterations in synaptic transmission play a role in the origins and treatment of stroke, depression, schizophrenia and epilepsy.
Postsynaptic regulation of neurotransmission
In studying the cellular and molecular mechanisms that allow our brains to learn and remember, Dr. Yu Tian Wang is changing researchers’ understanding of how signals are transmitted throughout the nervous system. Dr. Wang recently came to BC – bringing 12 members of his lab with him – to set up a new laboratory at UBC’s Brain Research Centre and continue his studies on how neurons (brain cells) communicate with one another. Neurons transmit information through a process known as synaptic transmission. Learning, memory and the creation of neural connections in the brain, as well as the development of many brain disorders, are all related to the strength of synaptic transmission. The functioning of neurotransmitter receptors, which are located at the receiving end of synaptic transmissions between neurons, is key to this process. When certain types of receptors, such as glutamate receptors, are understimulated, communication between neurons is decreased and may lead to diseases such as Alzheimer’s; when these receptors are overstimulated, such as during a stroke or epileptic seizure, neurons may die. Dr. Wang’s work has challenged the traditional understanding that the primary way to affect transmission strength between neurons is to increase or decrease the functioning of the receptors. Instead, he has found that some physiological and pharmacological factors, such as certain hormones, can actually alter the number of receptors found on the neuron’s surface and affect transmission strength. This research has many potential applications. For example, enhancing the number of receptors in the brains of people with Alzheimer’s, or in children with neurological disorders, could enhance learning and memory. Decreasing the receptors could protect against brain cell death following a stroke.
Functional interactions between basolateral amygdala and mesocortical dopamine inputs to the medical prefrontal cortex: Electrophysiological and behavioral analyses
As part of a complex, interconnected neural network, the brain’s prefrontal cortex plays an important role in integrating emotional information for complex forms of cognition, such as planning, behavioural flexibility, decision-making and working memory (e.g. remembering a phone number just long enough to write it down). The amygdala — a brain structure residing in the temporal lobe — provides emotional information to the prefrontal cortex. Mesocortical dopamine transmission in the frontal lobes is also important in higher order cognitive processes. Dysfunction of the brain’s emotional and decision-making circuits is believed to be closely linked to diseases such as schizophrenia and drug addiction: patients with these disorders can show structural abnormalities in the prefrontal cortex and the amygdala, decreased levels of cortical dopamine and impairments in emotional processes. Dr. Stanley Floresco is investigating the mechanisms through which emotional and decision-making circuits operate, and how their functioning is modulated by mesocortical dopamine. By shedding light on normal functioning in the brain at a cellular and behavioural level, these studies will increase understanding of the processes that underlie abnormal brain function in many psychiatric diseases.
Molecular pathology of familial gastric cancer
Dr. David Huntsman is one of a growing number of health researchers who are equally interested in answering research questions and translating their findings into better clinical care. As a clinician scientist, Dr. Huntsman identifies and studies susceptibility genes for cancer – specific genes that increase a person’s risk for getting a certain type of cancer. Previously, he and his research team detected mutations in a gene called E-cadherin in one-third of families with extreme histories of early onset stomach cancer. This information was used as the basis for offering prophylactic stomach removal for at-risk individuals with one of these mutations. In all 11 individuals who elected to have their stomach removed, Dr. Huntsman’s team discovered tiny, early cancers, undetectable by current diagnostics. Dr. Huntsman is now working to identify new susceptibility genes for stomach cancer so more at-risk families can be medically managed. He is also studying the role of another gene, EMSY, in breast, ovarian and other cancers. His findings may lead to clinical advances in the diagnosis and treatment for many types of inherited cancer.
Investigations of Parkinson’s Disease with quantitative high resolution PET imaging
Affecting approximately 80,000 Canadians, Parkinson's disease is characterized by the lack of the neurotransmitter dopamine in the brain. Symptoms include progressive impairment of motor function and a significant impact on quality of life. Dr. Vesna Sossi is a medical physicist who brings her expertise in the physics of nuclear imaging to advance understanding of the pathogenesis, progression and specific manifestations of Parkinson's disease, as well as the biochemical results of therapeutic interventions. Currently, she is developing a new method for using Positron Emission Tomography (PET) to study the dopaminergic system (the brain's production and use of dopamine) at varying stages of the disease. PET is a non-invasive diagnostic imaging technique for measuring the metabolic activity of cells in the human body. In addition to providing information about disease progression, this work may provide important insights into how the brain compensates for decreased dopamine levels during early stages of Parkinson's.
Statistical techniques for genomic research
Genomics is the study of how the information contained in a genome gives rise to organisms and their functioning. This relatively new field of research analyzes vast amounts of data to uncover biological trends that help scientists understand how genes function in living systems. Dr. Jenny Bryan is working to develop new quantitative methods and statistical frameworks required for analysis of large functional genomics data sets. Her work addresses how researchers can find patterns and themes in complex, multidimensional genomic data. With colleagues, Dr. Bryan has pioneered methods of statistical gene expression analysis and has created a software program to implement these methods. Her software is currently being used by the world’s second largest biotechnology company. After she completed her PhD in 2001, Dr. Bryan elected to join Vancouver’s burgeoning computational biology and genome sciences community. Along with her dual appointment in the UBC Biotechnology Laboratory and Department of Statistics, she is also a faculty member in the MSFHR/CIHR Strategic Training Program in Bioinformatics.
Children’s mental health: Linking research evidence and policy making
How can we ensure that public policies in children's mental health reflect the best available research evidence about what works to help children. This is the research focus for Dr. Charlotte Waddell, who is exploring ways to strengthen the links between new research knowledge and policy making. At any given time, up to 20 per cent of children experience mental health problems that affect their emotions, learning and behaviour, and interfere with their development. This creates a large burden of suffering for these children, their families and their communities. However, there are often few links between the realms of research evidence and policy making in children's mental health: research evidence is often poorly communicated to policy makers, and policy makers often make decisions that contradict the best available research evidence. Dr. Waddell is investigating the respective needs and working cultures of researchers and policy makers, and will suggest and test new ways for these two groups to share information better. The goal of her work, supported by MSFHR, the Canadian Population Health Initiative and the BC Ministry for Children and Family Development, is to ensure that more effective interventions are available to help children at risk. Her findings will apply to many other health arenas where improved links between research and policy making are also needed.
Studying the health care workers: A program of research on the relationships between work and health
The face of health care and the working environment for health care workers in Canada is changing, bringing increasing job complexity, an aging work force, changes in the delivery of patient care, and concerns for employee recruitment and retention. These changes have been coupled with cost containment strategies – such as restructuring – that alter the resources that staff have available to do their work. Dr. Mieke Koehoorn’s research focuses on how the work environment affects the health and well-being of health care workers in BC. She is using the BC Linked Health Database in conjunction with hospital employee and survey data to create a comprehensive population-based, person-specific, longitudinal database of health care workers. The database, recording information such as health care utilization, workers’ compensation and long-term disability records, is unique in its depth and breadth. Dr. Koehoorn is using this information to describe the health and health care utilization of health care workers and investigate the workplace practices and conditions that predict health outcomes. By understanding the complex determinants of health for health care workers, Dr. Koehoorn hopes to help inform industry decision-makers to allocate resources and implement workplace policies and procedures that improve employee health and performance and reduce work-related disability.
The impact of changing work and community conditions on the health of workers and their children in BC resource dependent communities
Health research has established a strong link between socio-economic status and health outcomes. However, in BC’s resource-dependent communities, the income and social status situations for many workers vary throughout their working lives as a result of changing technologies and labour market conditions. Downsizing and restructuring in the labour market often results in greater frequency and duration of unemployment. Workers who retain their jobs often experience increased work stress in adapting to new on-the-job requirements, and entire resource-based communities are affected when industries downsize and restructure. Dr. Aleck Ostry is focusing on the health of workers in resource-based industries, and the health of their children. Dr. Ostry is studying the health outcomes of more than 28,000 sawmill workers between 1950 and 1998 in 14 BC sawmills, as well as approximately 23,000 of these workers’ children. He will explore to what extent labour market experiences at work and in the community affect the health outcomes of workers, and how these experiences also affect the health of their children. As changing market conditions in the global economy affect workforces throughout the world, this research is gaining national and international recognition.