Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide and affects ~1% of Canadians. Its chronic inflammation causes pain and joint failure, eventually leading to disfiguration and disability. The cartilage and bone destruction of RA is thought to be caused by a certain family of enzymes, MMPs, that are capable of breaking down all joint components, causing severe damage and pain. Recently, 14-3-3 proteins were discovered to be critical communication proteins between skin cells during the healing process. 14-3-3 proteins also stimulate production of MMPs. Thus, the abnormally high amounts of 14-3-3 found in RA joints might be responsible for excess MMPs production, which leads to joint destruction. Jennifer is studying how 14-3-3 proteins may stimulate production of MMPs and lead to the joint destruction in RA. Ultimately, her work will contribute to the development of novel therapeutic strategies to diagnose and treat RA and other arthritic diseases.
Year: 2006
The role of p53, p63 and p73 in the survival of oligodendrocytes following spinal cord injury
Spinal cord injury can be characterized into two broad pathological events known as the primary injury, typically a blunt force trauma, and the secondary injury, an ensuing degradation of both neurons and glial cells. The secondary injury is characterized by vascular alterations, poor blood flow, production of free radicals, oxidative stress, ionic imbalance, inflammation and excitotoxicity, which has a very large impact of the survival of oligodendrocytes, the cells responsible for myelination in central nervous system. These event occur days to weeks following the injury making them suitable for pharmacological intervention. Recent work has implicated p53 and p63 as pro-apoptotic (programed cell death) and p73 as antiapoptotic for neurons. Using animals which are absent of these factors specifically in oligodendrocytes, I wish to examine their affect on the survival and apoptosis of oligodendrocyte following a spinal cord injury. I also wish to correlate this difference in oligodendrocyte survival and apoptosis to the behavioural outcome of these animals. This will enable the validation of p53, p63, and p73 as targets to promote survival of oligodedrocytes following spinal cord injury. lf that is the case, it would suggest the need to develop novel treatments that target these proteins for potenetial future clinical application.
Physical Activity, Local Joint Factors and Osteoarthritis
Osteoarthritis is a leading cause of disability in Canada. This type of arthritis causes deterioration in the joints, leading to swelling, pain and stiffness. It often results in lost work time and places limits on an individual’s normal function and recreational activity. Both the increasing prevalence of osteoarthritis in the province’s aging population, and the lengthy surgical wait times for replacing osteoarthritic joints are high profile health care issues in British Columbia. Physical activity can offer almost universal improvements in health, which includes decreasing the risk of heart disease, stroke, high blood pressure and cancer. Health Canada recommends all adults participate in at least 30 minutes of moderate-intensity exercise most days. But some types or too much physical activity, such as competitive sports or heavy physical work, can cause excessive wear and tear in the joints, increasing the risk of osteoarthritis. In addition, some people may be more vulnerable to the type or amount of physical activity because of the way their legs are aligned (e.g. bow-legged) and/or because of increased flexibility (hypermobility). Chuck Ratzlaff is comparing data on lifetime physical activity and these joint factors in people with knee and hip osteoarthritis to those who don’t have the condition, as part of a national arthritis study. The results can be used to recommend appropriate amounts and types of physical activities that may decrease the risk of osteoarthritis of the hip and knee.
The effect of a province wide, school-based physical activity initiative on the behavioral symptoms of Attention-Deficit Hyperactivity Disorder (ADHD) in children
Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed psychiatric disorders of childhood. Children with ADHD have a high rate of disciplinary problems in school, experience social and academic difficulties, and encompass 30 to 40 per cent of referrals to child guidance clinics. Given the frequent occurrence of ADHD and the issues associated with it, effective and appropriate treatment has become a critical issue. With the desire to provide a healthy and effective solution in treating the symptoms of ADHD, Nicole Smith’s study is exploring the effects that repeated physical activity may have on the symptoms of ADHD in a practical setting. Using a standardized ADHD questionnaire, parents and teachers will indicate the degree of influence a long-term, province-wide, school-based physical activity initiative has on the behavioural symptoms of children with ADHD while in their classroom and home environments. The primary goal of Nicole’s research is to evaluate the effect of school-based physical activity intervention on ADHD symptoms and classroom disruption among children ages 9 to 12 with ADHD. Since little research exists on the impact of exercise on the behavioural symptoms of ADHD in children, there is potential for this research to make a significant contribution in the areas of child mental health, ADHD health promotion and intervention.
Prenatal Alcohol Exposure: Fetal programming, stress responsiveness, and vulnerability to depression and addiction
Women who consume large quantities of alcohol during their pregnancy can deliver babies with Fetal Alcohol Syndrome (FAS) or Alcohol Related Neurodevelopmental Disorder (ARND). Adults with FAS/ARND can exhibit a range of motor, behavioural and neurodevelopmental deficits. They also have higher rates of addiction and depression compared to the normal population. However, the relationship between prenatal exposure to alcohol and these psychiatric conditions is not known. One consequence of prenatal alcohol exposure (PAE) is re-programming of the neural system involved in stress, known as the hypothalamic-pituitary-adrenal (HPA) axis. Activation of the HPA axis during stressful situations is, in the short term, an adaptive response. But prolonged activation or an inability to “shut off” this system can have drastic consequences on brain function and behaviour. HPA dysfunction is implicated in the cause of depression, and activation of this system through stress can influence the initiation and maintenance of, as well as relapse to, drug addiction. Kim Hellemans is exploring how changes in the neural wiring of the HPA through PAE influences behaviours and neuroendocrine function associated with addiction and depression. Early targeting and prevention of psychiatric conditions is a critical goal of health research; the aim of Kim’s research is to determine whether normalizing HPA dysfunction in children with FAS/ARND can prevent their vulnerability to depression and addiction in adulthood.
The role of perfectionism, stress, and interpersonal discord in chronic headache disorders: A daily process study
Headache disorders are a prevalent health issue affecting between 10 to 35 per cent of the Canadian population. Headache disorders—which range from migraines to tension headaches—are associated with significant emotional, social and economic costs, including lost work days, decreased productivity and increased health care costs. There is increasing interest in understanding the role of psychosocial influences, such as personality traits, interpersonal interactions, coping and stress, in the onset, frequency and severity of headaches among sufferers. Perfectionism is a personality trait that has been identified as a potential risk factor for headache disorders. Perfectionists tend to experience greater stress due to their high expectations, self-critical tendencies and interpersonal conflict. Dayna Lee-Baggley is examining how perfectionism may generate and magnify risk factors (e.g., stress) for headache episodes. Her study is the first to monitor perfectionists’ experience of headaches on a daily basis. By identifying the risk factors associated with headache disorders, Dayna’s research will allow researchers to identify targets for intervention that could prevent or minimize the occurrence and impact of headaches for a substantial group of people.
Early Nutrition, Language and Cognitive Development
Large amounts of omega-3 fatty acids are essential to support fetal and infant brain development. Omega-3 fatty acids accumulate in the central nervous system in the developing infant brain during and after pregnancy, although the brain appears to be particularly sensitive to dietary deficiencies of important essential fatty acids during intrauterine development. Before birth, essential fatty acids (those fatty acids which humans cannot form and which must be obtained from the diet) are transferred through the placenta, and after birth, through breast milk. The intake of omega-3 fatty acids in western diets is low with research demonstrating that many women following typical western diets likely have lower intakes than what is required by the developing infant before birth. Current guidelines for intake of Omega-3 fatty acids are directed at reducing the risk of chronic diseases like cardiovascular disease, and do not consider the needs of pregnant and lactating women, or the important role of omega-3 fatty acids in brain development and function. Dr. Orly Lipka is investigating whether an increase in omega-3 fatty acids during pregnancy reduced the risk of poor neurodevelopmental outcome in infants. Her research involves the use of sensitive tests of early language and problem solving ability to assess subtle delays in development secondary to nutritional deficiency during prenatal development. An important part of this work is also following up to assess the later effects in early childhood. The findings should lead to better understanding of the importance of omega-3 fatty acids with respect to cognitive and behavioral development.
Nuclear liver X receptors in the pathogenesis of, and the innate immunity against Samonella enterica
Salmonella enterica infections represent a serious public health problem. This bacterium causes diseases ranging from typhoid fever to food poisoning, affecting millions of people each year. Currently, there is little understanding of how Salmonella causes disease and the role of the immune system during the infection. The innate immune system is the first line of defense against pathogens, and is considered to be very important in defining the outcome of Salmonella infection. Recent evidences suggest that important components of the innate immune responses are modulated by some of the same elements involved in the control of various metabolic pathways. Previously, Alfredo Menendez was funded by MSFHR for his PhD research into the generation of a prophylactic vaccine against HIV-1. Now, Alfredo is studying the innate immune response against Salmonella, and the interplay between the control of inflammation and metabolism in the setting of Salmonella typhimurium infection, in vitro and in vivo. Research in this field may lead to the development of improved or novel treatments or vaccines for Salmonella through the enhancement of the innate immune response
To Each Her Own: Sex Work Typologies, Intimate Relationships, and their Impact on HIV Risk for Female Sex Workers in Vancouver's Downtown Eastside
The estimated 1,000 female sex workers in Vancouver’s Downtown Eastside (DTES) live in Canada’s poorest neighbourhood, characterized by deplorable housing conditions and high rates of hepatitis C and HIV infections. HIV prevalence is an alarming 26 per cent, according to a recent study of 198 female sex workers in the DTES. Although violence, poverty and social marginalization have been identified as putting these women at risk, we know very little about two of the defining issues that characterize sex work and make these women vulnerable to HIV: types of sex workers, and the intimate relationships women form with boyfriends and regular clients. Treena Orchard is exploring whether there is a link between a particular type of sex worker and relationship structure that places certain groups of women at greater risk for HIV infection. Her hypothesis is that women with an established sex work status are more likely to form lasting relationships and avoid high-risk sexual practices. Treena’s research is examining how different types of sex workers are identified and organized, and how these women construct and attach meaning to their intimate relationships, especially in relation to the issues of sexuality, health and trust. This study will use individual interviews, focus groups and social mapping to determine the broader social processes and health determinants that structure the HIV risk of these female sex workers. Examining the social organization of sex work and relationships in this context is critical to improving the women’s health status and developing HIV prevention programs that are population and gender-specific. As one of the few qualitative studies to address these issues among Canadian sex workers, this research will be relevant to other researchers, health authorities and – through their participation – the women themselves.
A prospective exploration of associations among cognitive dietary restraint, cortisol excretion, ovarian function and bone health in premenopausal women
About 16 per cent of Canadian women over age 50 have osteoporosis – a condition with low bone density that increases their risk of fracture. Osteoporosis costs the health system $1.3 billion annually, and both prevalence and costs are expected to rise in the next two decades as the population ages. Optimizing peak bone mass during women’s younger years is key to preventing osteoporosis. In western culture where thinness is idealized, many women experience body dissatisfaction. In response, women attempt to control their body size and weight, typically through diet and/or exercise. The eating attitudes of many women are characterized by high levels of cognitive dietary restraint (CDR) – the perception that one is constantly monitoring and attempting to limit food intake in an effort to control weight. While the adverse consequences of clinical eating disorders (e.g. anorexia nervosa) are well-recognized, the potential health effects of subtle disturbances of eating attitudes, such as high levels of CDR, are only beginning to receive researchers’ attention. Jennifer Bedford is studying whether these eating attitudes affect young women’s bone density. Previous research in the area suggests that women with high CDR have higher levels of the stress hormone, cortisol, which may negatively affect bone density directly by disrupting bone and calcium metabolism. It also affects bone indirectly by disturbing the menstrual cycle hormones, resulting in disturbances in ovarian function. Jennifer is conducting the first prospective study to examine the relationships between eating attitudes, cortisol levels, ovarian function and bone density in young women. The findings should lead to health and nutrition education strategies to inform young women of the potential health effects of their attitudes about food, eating and their bodies.