Who has Epilepsy in British Columbia?

According to national surveys, an estimated 30 per cent of Canadian children between six and 18 years of age suffer from chronic conditions and/or disabilities, including seizure disorders. However, these surveys do not allow for provincial analysis, due to small sample sizes, and there is limited comparability between surveys because of differences in target groups, methodologies and conceptual frameworks. Currently, there are no comprehensive prevalence data on children with special health care needs in BC, such as children with epileptic seizures, who account for half the visits to specialists because of neurological disease. Veronica Schiariti is researching the influences of neighbourhood income, population density, health care availability and community resources on the treatment prevalence of epilepsy in BC children under the age of 19. She is examining both diagnosis and treatment patterns of pediatric patients with epilepsy. Veronica hopes that her research will contribute to improved treatment for epileptic children by identifying disparities in health service delivery, informing health care policy decisions, and enabling long-term tracking and study of health and development outcomes at the individual level and in the broader population.

Optimizing the Role Nurses Play in Preventing Pediatric Deaths: An Application of Situational Awareness

Up to 23,000 preventable deaths are estimated to occur each year in Canadian hospitals. Nurses who provide care at the bedside are well positioned to promote patient safety, because a critical component of their role is to notice and gauge potential risks. Although research suggests that nurses’ workload, training and experience influence patient mortality, little is known about the actual processes that nurses use to prevent or reduce error. Kim Shearer is applying the model of “Situational Awareness” (SA) to study pediatric nurses performing resuscitation of children in hospital. SA – defined as knowing what is going on in your environment – has been proposed as the primary basis for decision-making and performance in complex, dynamic systems, helping researchers understand how threats within the environment are gauged and safety is facilitated. Kim’s study will identify factors that promote or impede nurses’ ability to gauge the work environment and make decisions, generating the basic knowledge needed to create computer simulations for teaching and testing SA in pediatric resuscitation. Findings of this research will help to prevent or minimize error and enable development of novel health education interventions to improve SA and hence the safety of children in dynamic and complex acute care environments.

Pharmacogenetics of Mycophenolate in Thoracic Transplant Recipients: Role of UDP-Glucuronosyltransferase Genetic Polymorphisms

Thoracic (heart and/or lung) transplantation is an effective but aggressive measure for treatment of end-stage heart and lung diseases. However, rejection of the transplanted organ remains a major problem and frequently leads to organ loss and death. All transplant recipients take immunosuppressants (drugs that prevent rejection), yet over-immunosuppression exposes them to undesirable infections and other side effects. Mycophenolic acid (MPA) is an effective immunosuppressant commonly used in transplantation. However, tailoring MPA therapy is challenging due to the wide variability and unpredictability in treatment responsiveness and side effects among patients. Genetic makeup and metabolism of MPA have a significant bearing on drug responsiveness. While many studies provide better understanding of MPA in kidney transplant recipients, information on the thoracic transplant population is scarce. Lillian Ting’s research is exploring the role of genetics in determining treatment responses. The ultimate goal is to individualize regimens, even before treatment begins, for each patient in order to obtain optimal treatment response and minimal toxicity. The results from Lillian’s study will add valuable knowledge to transplantation management. It will be directly incorporated into patient care, improving patient survival and quality of life after transplantation.

Abnormal brain development in premature newborns

Many children who have been born prematurely experience long-term cognitive, visual and motor deficits. A number of interrelated factors that commonly follow preterm birth are believed to contribute to neurodevelopmental impairment, including newborn illness and exposure to medications, abnormal brain development in the months following birth, and a characteristic type of brain injury known as white matter injury. Currently, there is little research regarding how white matter injury and abnormal brain development lead to impaired motor and cognitive function. Dr. Steven Miller is researching brain development and injury in premature babies to understand how such injuries occur and why specific brain regions are affected. Using magnetic resonance imaging (MRI) techniques, Dr. Miller is measuring brain development and white matter injury in premature newborns shortly after birth and then again when the newborns reach term-equivalent age. Subsequent tests measuring gross and fine motor skills, language and cognition will be conducted at 18 and 36 months of age to evaluate neurodevelopmental outcome. The results of this study will provide a better understanding of the factors impacting brain growth and injury in newborns, and lead to improvements in preventing or treating brain injury in this population. Dr. Miller’s research group also studies brain development and white matter injury in other groups of newborns at high risk of neurodevelopmental impairments, such as those with heart birth defects.

The exploration of genetic conditions affecting the health of aboriginal people

Canadian aboriginal people have shorter life spans and an increased burden of disease compared to their non-native Canadian counterparts. As in all populations, complex disease—both genetically and environmentally determined—plays a significant role. For example, among the Inuit of Baffin Island, the prevalence of one type of congenital heart defect is four times as high as in other populations.

Dr. Laura Arbour is exploring the genetic and environmental determinants of heart defects among the Inuit of Baffin Island. She will determine the contributing factors of genetics, intake of nutrients that are important in heart development (such as folate and vitamin A) and environmental exposures during pregnancy. She will also assess whether current public health efforts to reduce birth defects by fortifying flour with folic acid are sufficient for people in a northern environment. The goal of her research is to inform public health efforts aimed at prevention, early recognition of symptoms and timely treatment.

The role of protein tyrosine phosphatase alpha (PTPa) in integrin signaling in fibroblasts

Communication between the outside and inside of cells relies on protein molecules (such as integrins) at the cell surface, which interact with the external environment and send signals to other molecules inside the cell. These molecules interact to form complex signaling cascades to effect appropriate cell responses. Protein tyrosine phosphatases (PTPs) are a family of proteins that play a critical role in cell signaling processes. Shirley Chen is investigating the function of PTPalpha, an important player in integrin signaling. This signaling pathway regulates cell growth, migration, and survival, and has been implicated in cancer development and progression. By studying the activity of PTPalpha-deficient cells in comparison to normal cells, she will learn more about the role of this protein in the integrin signaling cascade. Since integrin signaling governs several aspects of how a cell responds to the environment, her study of this process will help reveal why certain cells, such as cancer cells, behave abnormally. In the long term, her research could contribute to understanding the onset and course of diseases such as cancer and diabetes, and may potentially lead to PTPalpha-based therapeutics for these diseases.

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 ‘junk DNA’ of unknown function. It is now known that the so-called junk DNA isn’t 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 ‘ultraconserved sequences’, 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.

Palmitoylation of ABCA1 and its effect on localization and function

Atherosclerosis is a slow, progressive disease caused by the buildup of plaque (fatty substances, cholesterol, cellular waste products, calcium and other substances) in the inner lining of the arteries. This plaque buildup can lead to heart attack, stroke or gangrene. Research has shown that high-density lipoproteins (HDL) remove excess cholesterol from plaque by transporting cholesterol away from the arteries and back to the liver, thus slowing the buildup. Higher levels of HDL seem to be protective against coronary artery disease, and thus HDL is sometimes referred to as “”good”” cholesterol. Dr. Roshni Singaraja is researching the role of the newly-discovered gene ABCA1, whose function is to to produce HDL. Specifically, she is investigating the role of the palmitoylation process (the attachment of palmitate – fatty acids – to proteins which acts as a signal for the protein to be transported) on ABCA1 and its function. In addition, Roshni will examine the function of ABCA1 in the brain and the impact of palmitoylation on these functions. Roshni’s research may lead to potential strategies to increase HDL production and to accelerate or reverse cholesterol transport in order to prevent atherosclerosis.

The American Society of Addiction Medicine – patient placement criteria, second edition revised (PPC- 2R) validity study in Canadian women

Mental health and addiction services have experienced frequent budget cuts in recent years, as governments try to contain health care spending. Yet, as Dr. Shimi Kang discovered during her earlier research at the World Health Organization in Geneva, Switzerland, substance use and mental illness are major global public health issues. The American Society of Addiction Medicine (ASAM) has developed a software program for making treatment decisions that consider resource issues. The program prompts interviewers to ask a series of questions, and produces recommendations for matching patients to the most appropriate treatment setting, based on standardized criteria. The software is now widely used in the United States, and studied in several other countries. However, the effectiveness of this assessment tool has never been studied within the Canadian health care system or with women, who experience different rates of addictive disorders and mental illness than men. Shimi is conducting the first Canadian study to evaluate whether the program can be applied to assess the complex biological, psychological and social needs of women with mental health and addiction problems. The results may lead to better techniques for treating drug and alcohol addiction and preventing relapse in women.

Role of the tumor suppressive E3 ubiquitin-protein ligase, Hace 1, in the development of childhood neoplasm

The onset and growth of a tumour may be due to the destruction of the balance that is normally achieved between tumour promoting and tumour suppressing factors. Recently, Dr. Poul Sorenson’s research team discovered a new gene, Hace1, from a case of Wilms’ tumour (the most common kidney tumour of childhood). They also found that Hace1 protein levels were reduced in 75% of the Wilms’ tumours analyzed, and that the restoration of Hace1 levels in tumour cells was capable of inhibiting tumour growth. These findings suggest that Hace1 is a tumour suppressive factor and that loss of Hace1 may contribute to the development of childhood tumours. However, the mechanisms by which Hace1 inhibits tumour formation are not yet understood. Current research suggests that Hace1 is an enzyme that specifically labels target proteins with small protein tag(s) called ubiquitin. It is thought that alterations of this process, as in the reduction of Hace1 levels observed in Wilms’ tumour, may lead to malfunctions of the target proteins and facilitate tumour development. Dr. Fan Zhang is testing this hypothesis through the identification of Hace1 target proteins and analysis of the Hace1 function in both normal and tumour cells. The knowledge derived from this study will help researchers understand how loss of Hace1 leads to the formation of childhood tumours which, in turn, may lead to new preventive treatment based on correcting the imbalance between tumour promoting and tumour suppressive factors.