There is little published information about Canadian children with HIV especially about the health-related needs of adolescents. Yet it is during this period when they begin dealing with issues such as disclosure, psychosocial therapy, HIV prevention and sexual health, that support is most needed. Sarah Fielden is examining the health needs of children with HIV and developing strategies to meet them. Her research involves conducting focus groups with children and adolescents, families and service providers to capture a range of perspectives on this issue, and to specifically explore factors in the health system and community that allow children and adolescents to “live positively”. Sarah’s aim is to help improve the health and health care of children with HIV, and assist health care providers, academics, organizations and families in developing effective, age-appropriate interventions.
Pharmacogenetics-the study of how genetic makeup affects an individual’s response to drugs-fascinates Evan Kwong. The field addresses the underlying causes of why drugs may affect people differently, bringing the study of genetics into a practical, clinical setting. In the future, having access to a patient’s genetic profile could help clinicians more quickly and accurately select the right therapy. Evan’s research focuses on the common painkiller codeine, which produces pain relief as it is metabolized into morphine by a liver enzyme. A genetic variation in 25 to 40 per cent of people of Chinese descent appears to be associated with decreased function of this liver enzyme. Evan hopes to determine whether people who carry this genetic variation metabolize codeine less effectively. With that knowledge, clinicians could offer other drugs that will be effective.
Vascular disease is the largest single cause of death in developed nations, and the incidence of cardiac valvular disease (disease in heart valves) is significant. The first cells to be adversely affected in vascular disease are endothelial cells, located on the inner lining of blood vessels. In the initial stages of vascular disease, there are modifications to the way endothelial cells regulate calcium signaling, an essential part of communication between cells. Willmann Liang is studying normal and abnormal calcium regulation in two types of heart valve cells: endothelial cells and myofibroblasts (cells involved in wound healing). Willmann aims to understand how calcium regulation in the human cardiac valve is altered with disease, and to determine how gene expressions governing the various components of calcium signaling are modified. Ultimately, the research may lead to the early prevention and treatment of valvular diseases.
The error-free duplication of a multicelled organism’s genetic material is critical to its survival. Even small changes in the genetic code during duplication can lead to diseases such as cancer. Equally important to cell division is the error-free transmission of chromosomes to each of the two daughter cells, which depends on the proper regulation of sister chromatid cohesion (the attachment of both strands of newly-replicated DNA to the area of the chromosome called the centromere). When the mechanisms involved in chromatid cohesion are defective, there may be uneven segregation of chromosomes to daughter cells. This results in abnormal chromosome numbers (aneuploidy), a characteristic of many cancers. Ben Montpetit is studying the components responsible for regulating cohesion of sister chromatids. Ben’s research is aimed at providing a better understanding of what happens when the cohesion process is flawed, and to help identify therapeutic targets in cells with defects due to altered chromatid cohesion.
Huntington disease (HD) is a neurodegenerative disorder that causes uncontrollable movements, impairment in memory and reasoning ability, and alterations in personality. Patients with the disease carry a mutation in the HD gene, which results in an expanded tract of glutamine (an amino acid). The gene product is therefore a mutated form of the HD protein. This expanded tract disrupts the interaction between the HD protein and other proteins that work together to perform essential cell functions. A modified interaction may alter the normal function of any of the interacting proteins, making specific cells vulnerable to premature death. Anat Yanai is studying the cell biology of several HD interacting proteins, including the way they interact with proteins involved in cellular metabolism and the alterations in their normal function as a result of the mutation in the HD gene. The findings will assist in developing therapeutic strategies for Huntington patients, such as inhibitors or activators of these interactions.
Based on her previous research on pediatric bone health, Dr. Kerry MacKelvie believes that perhaps the greatest hope for preventing osteoporosis in later life is to intervene during childhood. Kerry has studied how high impact exercise affects bone mass and structural changes during growth, and she has investigated the effects of ethnic background on bone health. Now Kerry is bringing together in one study an investigation of all the factors that may contribute to bone strength during childhood: exercise, hormones, body mass and composition, and ethnicity. She will study Asian and Caucasian boys who have not yet reached puberty, focusing on bone mass changes over time for both overweight boys and inactive boys. The study is particularly relevant to Vancouver’s population, as it will examine and compare ethnic-specific hormonal, body composition and bone mass changes during growth in both Asian and Caucasian children.
Along with the completion of the Human Genome Project have come new insights and tools to understand complex gene interactions. Dr. Louis Lefebvre’s work focuses on genomic imprinting, an inheritance process that works counter to the traditional genetic rules. Genes are inherited in two copies – one from the father and one from the mother. Usually, the outcome in the offspring will depend on whether genes are dominant or recessive. With certain genes, however, the inheritance is parent-of-origin-specific: the gene will always be inherited by either the mother or father, with the corresponding gene from the other parent maintained in a silent state. This type of inheritance is thought to be especially important for the development of the embryo and in adult tissues. Defects in imprinting are associated with a variety of disease syndromes. Dr. Lefebvre is studying the mechanisms of genomic imprinting. He hopes to identify new genes required for normal development and better understand the origins and causes of human syndromes that are associated with abnormal imprinting.
Dr. Ruth Grunau is a world expert on the measurement and long-term consequences of pain in newborns and premature infants in neonatal intensive care units. From the late 1980s, when she conducted landmark research on measures for assessing pain in infants, she has continuously added to the body of research concerning how early pain experiences in very low birthweight infants may affect their clinical and developmental outcomes. Dr. Grunau is conducting several studies on pain and stress in fragile premature infants whose medical care involves repeated exposure to invasive procedures. She is studying how to distinguish pain from stress in very premature infants, and how pain, sedation and analgesia may affect their neurobehavioural development. She is investigating the effects of repetitive pain on attention, behavioural organization and development in very premature infants and toddlers. Finally, she is studying whether positive maternal interaction may moderate the potentially negative effects of neonatal intensive care unit experiences. By learning the most effective ways to minimize any detrimental consequences caused by early repetitive pain and stress, Dr. Grunau’s goal is to help clinicians improve the short- and long-term outcomes of very premature infants.
Dr. Ala Aoukaty has spent nine years investigating anti-viral and anti-tumour cells. Aoukaty’s doctoral research focused on understanding the signalling process that occurs after receptors on the surface of cells are engaged. That experience provided him with a strong background to conduct postdoctoral research on X-linked lymphoproliferative disease (XLP), a fatal disorder caused by a genetic mutation and characterized by severe infectious mononucleosis, immune deficiency and malignant lymphomas (tumours). A large Aboriginal family that carries the genetic mutation has been identified. Aoukaty will isolate and study cells from XLP patients and carriers of the disease in the family to study the abnormal immune responses at work. The research will shed light on how the immune system specifically responds to Epstein-Barr virus, which causes infectious mononucleosis, provide insights in general about lymphoproliferative disorders (diseases of immune system tissue), and enable the testing of gene replacement therapies.
Chromosome segregation is a fundamentally important process for human cells. When cells divide, they normally ensure both daughter cells receive one copy of each chromosome. But defects in this process can cause cells to lose chromosomes or receive extra ones. Inaccurate chromosome segregation can lead to diseases such as cancer. Despite the importance of this process, researchers are just beginning to identify and understand the genes and molecular mechanisms involved. Dr. Kristin Baetz is investigating the genes and mechanisms needed to ensure accurate chromosome segregation. Baetz is developing a genomic screen to identify unique genes in a genetic yeast model, whose genome and cell biology are remarkably similar to that of humans. Building knowledge about chromosome instability could lead to new treatments for common forms of cancer.