B lymphocytes (B cells), which develop from stem cells in the bone marrow, are specialized immune cells that produce antibodies to fight infections. After developing they move into the blood stream where their role is to detect pathogens and be activated by the encounter to mount an immune response against infectious microbes. An important cellular process called adhesion is involved with the development and activation of B cells. Adhesion is the process whereby receptors on the surface of the B cells bind to receptors on the surface of other cell types. A protein called Rap acts as a molecular switch that cycles between an âonâ or âoffâ state to regulate cell adhesion. Kevin Lin is studying the mechanisms of how Rap regulates B cell adhesion and cytoskeleton remodeling. In particular, he is investigating Rapâs control of the activation and function of Pyk2 (nonreceptor protein tyrosine kinase), believed to be involved in regulating the form and structure of the cell in response to antigen binding and chemokine signaling. This work will provide new insights into processes that regulate the development and activation of B cells, and may be important for a better understanding of inflammatory responses, autoimmune diseases, cancer of B cells, and other immune related diseases.
Year: 2005
Injection site infections of injection drug users in Vancouver's downtown eastside
In addition to other serious health risks experienced by Canadaâs estimated 125,000 injection drug users, individuals who inject drugs commonly develop infections at the site of injection, such as abscesses and cellulitis (infection of the skinâs deeper layers). Previous studies have shown these injection site infections account for the majority of admissions to emergency departments and hospital beds in Vancouver. Treatment is inefficient and costly, and these infections can lead to more severe complications, including bone infection, amputation and death. Surprisingly, there has been little research on preventive measures. Now, Elisa Lloyd-Smith is studying which individuals are at increased risk for injection site infections, and what preventive measures and treatments are most effective. She is also assessing whether the supervised injection facility in Vancouver’s Downtown Eastside community, the first in North America, reduces hospitalizations due to injection site infections. This is the first study anywhere in the world to evaluate the impact of a safe injection site on infection rates. Elisaâs research will identify preventive measures to reduce the incidence of injection site infections, improve health outcomes among injection drug users, and reduce health care costs.
Investigating the role of the O-GIcNAc post-translational modification in protein function and specifically in the etiology of type II diabetes
Sequencing the human genome has led to the realization that a relatively small number of genes can give rise to an enormously complex living organism. This can be explained by the fact that proteins can be modified after their initial assembly to have multiple functions in multiple locations in the co-ordination of cell growth and function. One such modification called O-GlcNAc has been shown to be involved in many cellular processes, however, its precise function has not yet been determined. Malfunctions in the regulation of O-GIcNAc-modified proteins have been implicated in such diverse diseases as diabetes, Alzheimerâs, Parkinsonâs, and a variety of cancers. For example, diabetic patients have been found to have elevated O-GlcNAc levels, although it is not clear whether these high levels are a cause or an effect of diabetes. Using techniques including mass spectrometry, chemical synthesis and mouse models, Matthew Macauleyâs goal is to develop a method for identifying proteins modified by O-GlcNAc. This will give valuable insights into how this modification process affects normal cell function and may provide new knowledge about its precise role (i.e. is it a cause or an effect) in diabetes. In turn, such knowledge may contribute to the development of more effective preventive and treatment strategies.
Exposure to air pollution and incidence of Acute Otitis Media in children
By age three, 80 percent of children in North America have experienced a middle ear infection, or otitis media. Symptoms include ear discharge, pain, fever, vomiting and diarrhea. This condition is the number one reason for young children to visit their doctor. Consequently, otitis media has high health care costs and is thought to contribute to overconsumption of antibiotics. The identification of preventable risk factors will aid in reducing the incidence of this common childhood disease, and the associated costs to our health care system. Known risk factors for otitis media include recent respiratory infection, age, gender, race, season, non-initiation of breast feeding, familial history, daycare enrolment, and exposure to passive smoking. Outdoor air pollution has been hypothesized as a risk factor. Elaina MacIntyre is conducting the first study in North America to investigate whether exposure to air pollution from industrial, traffic and residential woodburning sources is linked to the incidence of otitis media in children under 2 years of age. She is examining the health records of 60,000 children in British Columbia born between 1999 and 2000 to see if episodes of increased residential air pollution correspond with increased rates of diagnosis for otitis media. If a link is found, Elaina will analyze the cost of cases attributable to air pollution.
Cultural variations in parent's beliefs about attention-deficit/hyperactivity disorder: Implications for assessment and treatment
Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common mental disorders in children. Three to five per cent of elementary school-aged children are diagnosed with ADHD, which is often accompanied by other learning disabilities or disorders. Children with ADHD display persistent inattentive, hyperactive and impulsive behaviours that are inappropriate for their age. Research shows medication and behavioral treatments can be effective in treating ADHD. However, little research has examined the factors that influence parentsâ acceptance of and adherence to these treatments. Treatment adherence is an issue, especially among Asian-Canadian families. Janet Mah is investigating cultural variations in parentsâ attitudes towards mental health disorders such as ADHD. She is comparing how parentsâ expectations for child behaviour affect treatment choices in Asian-Canadian and Caucasian families. Janet will assess whether Asian-Canadian parents are less likely to attribute problem behaviour to medical causes, and more likely to feel a sense of stigma about mental health problems, compared to Caucasian parents. This research could help clinicians improve cultural sensitivity in mental health services to better reach the under-served population of Asian-Canadian families.
Emotion regulation among caregivers: Implications for psychological and physical health
Mounting evidence indicates that taking care of a spouse with a chronic disease increases the caregiverâs 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.
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.
UV exposure and effects of gene interactions with UV exposure as risk factors in Non-Hodgkin's lymphomas (NHL)
Non-Hodgkinâs lymphomas (NHL) are cancers of the lymphatic system, which is responsible for the bodyâs immune response to fight disease. People with suppressed immune systems are at increased risk for Non-Hodgkinâs lymphoma, but little is known about other risk factors. Some evidence points to ultraviolet (UV) exposure from sunlight as a possible risk factor. For example, the incidence of NHL has increased in parallel with some skin cancers. The risk of these skin cancers and NHL increase with proximity to the equator, suggesting sunlight or UV exposure is a risk factor in NHL, as has been proven for skin cancer. Certain groups with higher exposure to sunlight have increased risk of developing NHL. And UV radiation is known to suppress the immune response, which is associated with NHL. Carmen Ng is investigating genetic and environmental risks for NHL. She is also examining whether variations in two genes, XRCC1 and MC1R, affect the risk of Non-Hodgkinâs lymphomas due to UV exposure. This study will help explain the causes of NHL, which can be used to develop preventive measures and better treatments for the disease.
In silico approaches for investigating mechanisms of gene regulation
More than 95% of the human genome is made up of non-coding DNA, historically dismissed as âjunk DNAâ of unknown function. It is now known that the so-called junk DNA isnât junk at all; in fact, it contains important information specifying how genes are regulated. Non-coding DNA sequences located adjacent to genes typically contain binding sites for proteins that act like regulatory switches, turning genes on or off in the appropriate cell types and under particular conditions. Errors in this process have been linked to diseases ranging from cancer to obesity. Recent studies have determined that there are a surprisingly large number of non-coding sequences that are highly conserved across the vertebrate lineage. These regions, termed âultraconserved sequencesâ, are almost identical in humans, rodents and fish. They have been minimally explored but appear to have an important role in regulating the expression of key developmental genes. Shannan Ho Sui is studying the properties of ultraconserved regions in the human genome to assess their potential role in gene regulation. Her research involves using bioinformatics techniques to find and analyze patterns in DNA sequences. By determining the properties of genes associated with ultraconserved regions, evaluating how frequently recombination occurs in these regions, and locating similarly highly conserved non-coding sequences in the fly and worm genomes, Shannan hopes to develop a model describing how and why these regions are maintained in the genome. Her research results will provide valuable insights into mechanisms of gene regulation that play important roles in development and disease.