Mounting evidence indicates that taking care of a spouse with a chronic disease increases the caregiver’s vulnerability to psychological and physical illness. Caregivers report poorer health and use medications for physical problems more than non-caregivers, and they are 63 percent more likely to die over a five-year period than non-caregivers. Little is known about the ways caregiving affects health and well being. However, it has been observed that some individuals adapt successfully to the role of caregiver, despite the multitude of social, economic, and personal demands it places on them. This variability in caregiver well-being suggests that there are important individual differences in responding to stressful situations. Teresa Marin is analyzing the daily impact of expressing or suppressing emotions on the mental and physical health of spouses caring for cancer patients. While a caregiver may routinely control negative feelings to avoid upsetting the spouse, research suggests that chronic suppression of negative emotions may increase distress in the long run, because it can limit communication and support within and outside of the marital relationship. Teresa believes that strategies for dealing with negative emotions may be an important link between the day-to-day demands of caregiving and long-term health. By determining how emotional and coping behaviours affect well being, clinical interventions can be designed to foster healthy adjustment among caregivers.
Research Location: University of British Columbia - Point Grey
Air pollution exposure of pregnant women and infants – where and how much?
Urban residents are exposed to air pollution from motor vehicles every day. Research suggests that elevated exposure to air pollution may contribute to the development of respiratory and cardiovascular disease, particularly in the elderly and children, and to adverse pregnancy outcomes. Exposure levels depend on how much pollution is in the environment, where people live, and their daily activities. For example, high levels of air pollution around urban homes near busy streets have been linked to low birth weight babies and preterm births. Elizabeth Nethery is specifically looking at the levels and effect of air pollution exposure on pregnant women in urban centres. While air pollution studies generally use computer models based on neighbourhood monitoring stations and home location to estimate individual exposures, Elizabeth is the first person to evaluate the accuracy of these estimates for pregnant women by comparing predicted to actual exposures. The results will provide more accurate information on the air pollution levels pregnant women inhale, and could lead to regulatory strategies, health protection measures, and policies to improve the health of women, children and the general population.
Stress and adult neurogenesis: neuroprotection by dehydroepiandrosterone (DHEA)
Mood disorders such as depression and post traumatic stress disorder are a major health concern in British Columbia, and around the world. Understanding the role of stress related to depression is a crucial step towards developing treatment strategies. From a biological perspective, stress-induced decreases in neuron (nerve cell) production in the adult brain have been associated with depressive symptoms. One line of research into treatment options is the use of a steroid hormone called dehydroepiandrosterone (DHEA) which has been shown to alleviate symptoms of depression. Steroid hormones are critical for the nervous system to develop and function normally, but relatively little is known about the actions of DHEA on the nervous system and how DHEA acts at the cellular and molecular level. Amy Newman is investigating how physiological levels of DHEA buffer the effect of stress in organisms in the brain. She is examining the effects of DHEA on stress-induced changes in the nervous system and on adult neurogenesis (development of nerve tissues). Ultimately, findings from this study may lead to the development of therapeutic advances to decrease neuronal loss in response to stress, and alleviate symptoms of depression.
Mechanism of valproic acid-induced hepatotixicity
Valproic acid is an anticonvulsant drug frequently prescribed to epileptic patients, and also used to manage bipolar disorder, migraine headaches and pain. Despite its ability to control seizures, the drug is associated with a rare, but potentially fatal liver toxicity. It is unclear how valproic acid causes liver failure, and health care professionals are unable to predict which patients will be affected, although it occurs more frequently in patients younger than two years of age who are also taking other anticonvulsant medications. Tony Kiang is researching the factors that cause and the mechanisms responsible for valproic acid induced liver failure in pediatric epileptic patients. The research could help physicians identify patients at risk of liver toxicity before prescribing valproic acid, so other medications can be used instead. The findings could also be applied to other drugs with similar side effects to improve their safety, and to identify compounds likely to cause side effects during drug development.
Glutamate regulation at the Drosophila larval neuromuscular junction: a model for excitatory synaptic function
The human brain is composed primarily of two cell types – neurons, which extend axons that make contact with other neurons at synapses, and glia, which wrap around neurons, protecting them and regulating their function. An electrical signal is conducted through the axon to the synapse where neurotransmitters are released to electrically excite the next neuron. The termination of this chemical signal is controlled by nearby glia, which remove the neurotransmitter using transporter proteins on their cell surfaces. A malfunction in this activity may lead to excessive levels of neurotransmitter accumulating in the synapse, over-exciting nearby neurons and glia and eventually leading to cell degeneration and death. This type of glial malfunction has been linked to many common neurodegenerative diseases (e.g. stroke, Alzheimer’s, multiple sclerosis and muscular dystrophy). Glutamate, the neurotransmitter at most brain synapses, is also present at many synapses of the fruit fly (Drosophila melanogaster). As in humans, fly glia have glutamate transporters that are thought to regulate synaptic communication. Robert Parker is studying glial neurotransmitter transporter function in the fruit fly, altering the amount of glutamate transporter present in glial cells near the Drosophila neuromuscular junction (a synapse between a neuron and a muscle cell) which may cause the over-excitation, degeneration and death of nearby cells. By studying the basic function of glutamate transporters in flies, he hopes to gain a greater understanding of the clinical importance of glutamate transporters in many human neurodegenerative diseases.
The effects of an acute bout of exercise on alpha-receptor responsiveness and orthostatic tolerance in hypertensive individuals
Hypertension (high blood pressure) is a major public health issue. About 22 per cent of Canadians have hypertension, a risk factor for numerous cardiovascular diseases, including stroke, coronary heart disease, kidney failure and narrowing of the blood vessels to the arms, legs and feet. Jessica Scott is examining the effects of exercise in people with mild or moderate hypertension. Previous studies have shown an eight to 10-week physical exercise program can dramatically reduce blood pressure in hypertensive individuals. But the striking decrease in blood pressure immediately following exercise may be dangerous for these patients. While standing, gravity displaces blood away from the middle region of the body and pools in the extremities, reducing the volume of blood available to the heart. Fainting after exercise as a result of this pooling in the extremities may be the first indication of a serious cardiovascular condition. Jessica is investigating whether a sudden drop in blood pressure predisposes people with hypertension to lose consciousness following exercise. Ultimately, she aims to develop a safer, more effective exercise program for people with high blood pressure.
Tracking the differentiation fate of islets from pancreatic endocrine progenitors via expression of lentivirally transduced fluorescent reporter genes
The recent success of a pancreatic islet cell transplantation procedure known as the ‘Edmonton Protocol’ gave new hope for a better treatment of type 1 diabetes (insulin dependent diabetes), compared to the current treatment via insulin therapy. However, a shortage of donor pancreatic tissue means an alternate source of transplantable cells is needed. Insulin-producing islet cells are created from pancreatic precursor cells through a process called differentiation. However, not all pancreatic precursor cells give rise to insulin-producing islet cells. Further, the optimal conditions for differentiating these cells have not been determined. This poses a challenge for researchers attempting to identify and isolate the specific precursor cells needed for producing transplantable islet cells on a large scale in the laboratory. Marta Szabat is working to develop a functional assay for tracking the differentiation fate of islets from pancreatic precursor cells using fluorescent reporter genes. This cell marking technique would flag only those cells with specific genetic characteristics, allowing for purification and further characterization of labeled cells. Using this functional assay, her long term objective is to determine the optimal conditions to support (culture) the differentiation of pancreatic progenitors into insulin-producing cells.
Computational identification and quantitative modeling of dynamic cellular pathways
The ability of cells to carry out life functions arises from the collective behavior of interacting molecules. Cells are able to integrate multiple internal and external messages simultaneously and respond reliably with a predefined set of outcomes. This adaptability and robustness is based on a complex system of signaling and regulatory molecules, which interact in dynamic circuits to regulate and support all aspects of cell growth and function. James Taylor brings a background in engineering physics to the study of molecular biological systems. He is using mathematical and computational modeling to simulate information flow through dynamic molecular circuits. In parallel, he is designing microfluidic platforms for the experimental testing of these circuits on the single cell level. James hopes to increase the efficiency of biological discovery and the use of predictive modeling in drug discovery. Employing filamentous form cell differentiation in yeast as a model system, he is characterizing the dynamics of a new circuit within the MAP Kinase cascade, a common signaling system that plays a central role in integrating the signals from a diverse group of external stimuli to regulate processes such as cell proliferation, cell differentiation, cell movement and cell death. Using a double headed approach of modeling and experimentation, he is continuing to research how this complex circuit enables the cell to robustly integrate multiple internal and external molecular messages simultaneously.
Back injury in heavy industry: Examining peak and cumulative back muscle activity for risk exposure assessment
Despite increasing technological advances, heavy industries remain physically demanding, with high back injury rates among workers. In BC, more than 17,000 compensation claims for back strain accounted for 25 per cent of all claims for 2001. More than a quarter of these claims come from employees in the forestry, wood and paper products, construction, transportation, and warehousing industries. Activities such as lifting, carrying or pushing objects subject workers to forceful exertions, repetitive movements and awkward postures, all of which can contribute to back injuries. Injuries are thought to be caused by both “peak” or maximal loads (such as lifting a heavy box once) and the total load over time (repeatedly lifting boxes throughout the day). However, most studies have focused solely on peak loads. Catherine Trask is conducting the first study to measure muscle loading over time among workers in these five heavy industries. Catherine is comparing how peak and cumulative muscle loads impact back strain, and whether total load is an important risk factor for back injury. The results may identify the maximum safe physical loads for workers in heavy industry, which would help reduce injuries, make industrial workplaces safer, and reduce claim costs.
The function of Pyk2 on Rap-GTPase mediated cell spreading and cell migration
B cells make antibodies that help combat pathogens. The B cell receptor, chemokine receptors and integrins on the cell surface are molecules that send signals to regulate B cell migration and adhesion. These processes are essential for B cells to enter the lymphatic system and to identify and adhere to foreign molecules (antigens) for the purpose of mounting a protective immune response. Proteins called Rap GTPases and Pyk2 are important in controlling B cell migration and adhesion, but the mechanisms involved are not well understood. Kathy Tse is investigating how Rap regulates Pyk2 and how Pyk2 promotes B cell migration and adhesion. Specifically, she is examining the localization and activity of Pyk2 during cell migration and adhesion. Knowledge from this study will allow better understanding of normal B cell movement and activation, and has potential for identifying drug targets for treating immune system diseases, including cancer.