Autism Spectrum Disorders (ASDs) are characterized by impairments in social interaction and communication, as well as restrictive behaviours and interests. These life-long disabilities affect more than 1 in 250 individuals. It has been shown that early diagnosis is essential for children with ASD: the earlier intervention is initiated, the better the outcome. However, affected children are commonly not definitively diagnosed until they are three years of age or older. Sibling, twin and family studies have shown that ASDs are largely genetic in origin and certain chromosomal regions harbouring possible ASD susceptibility genes have been identified. Recent studies suggest that between 5 and 48% of individuals with autism exhibit chromosomal anomalies. This suggests that small chromosomal anomalies, such as microdeletions and microduplications, may be relatively common and clinically important markers for identifying underlying causes of, and susceptible gene regions for, ASDs. Dr. Suzanne Lewis is researching the genetic susceptibilities of ASD, using a novel method for the analysis of regional changes in DNA called microarray-based comparative genomic hybridization (array-CGH). Using this method she is identifying and characterizing chromosomal abnormalities in 100 subjects with ASD. In parallel, Dr. Lewis is also researching ASD phenotypes – genetic influences in combination with respective behavioural, physical, medical, environmental and family findings. Dr. Lewis aims to build a research pathway that identifies genetically distinct subgroups of ASD that also share unique clinical phenotypes. Through researching this genotype/phenotype correlation Dr. Lewis ultimately hopes her research will contribute to a better understanding of the genetic causes and consequences of autism and help in developing methods for the very early identification of infants and families at risk for autism.
Year: 2005
Evaluating socioeconomic status differences in patient preferences for asthma therapy using discrete choice experimentation
Asthma is one of the most common chronic conditions affecting Canadians. Despite the availability of effective therapies and guidelines on how to manage asthma appropriately, poorly controlled asthma remains a significant health issue, with morbidity (complications) and death rates continuing to increase both in Canada, and worldwide. Dr. Larry Lynd’s previous research identified that asthmatics of lower socioeconomic status are more likely to have poorly controlled asthma. Building on his previous work, Dr. Lynd is now studying the factors that may be contributing to these differences, using a novel methodology called Discrete Choice Experimentation, originally developed for market research. Study participants complete a questionnaire which is designed to determine their individual preferences for different aspects of asthma management. The questionnaire asks questions related to areas such as avoiding side effects, realizing a benefit from drug therapy, and how much individuals are willing to pay to achieve these outcomes. By comparing this data with their socioeconomic information, Dr. Lynd hopes to determine if there are differences between individual’s preferences are based on their levels of education and household income. The results of this study will provide further insight into some of the factors that may be contributing to poorly controlled asthma, which in turn will contribute to the development of specific programs and interventions aimed at improving asthma control and outcomes. This study is one component of Dr. Lynd’s broader research program involving the development and application of new methods for therapeutic risk-benefit analysis.
Understanding community capacity in mental health reform through an examination of the gendered dimensions of the Riverview redevelopment process in British Columbia
Recent mental health reforms in British Columbia have resulted in a shift in the way services are delivered to people with serious and chronic mental health problems. Specifically, the main source of care for people has shifted from the provincial psychiatric hospital (Riverview Hospital) to smaller care facilities located in various regions throughout the province. Dr. Marina Morrow is studying the impact of these service changes on various groups affected by deinstitutionalization by examining the experiences and needs of recipients of mental health services, family members of people with mental illness, mental health care providers, administrators, advocates, and community members. Dr. Morrow is particularly focussing on issues relating to gender, and how the needs of women and men leaving Riverview Hospital might differ. Dr. Morrow is also examining the capacity of the current mental health system to respond to individuals, that have been newly discharged from Riverview, to ensure their successful integration into communities, and how the system can provide community-based support to individuals who become ill in the future. Dr. Morrow hopes the results from her research will contribute to improving the mental health care system’s response to people with serious and chronic mental health problems so that they can live full and productive lives in their communities.
Understanding the role of cryptochromes in human circadian phototransduction
The human eye is much more than the organ of vision. In addition to the machinery of the eye that allows us to see, the retina also houses photoresponsive molecules (photoreceptors) that mediate non-visual, light-driven signaling pathways. Our biological clock is regulated by the input of these light signals, including the circadian (24-hour) oscillation of our biochemistry, physiology, and behaviour. Many human functions rely on circadian rhythm and its accurate synchronization with the outside world by light (circadian phototransduction), including sleep, hormone regulation and brain function. Despite its central role in human health, however, virtually nothing is known about circadian phototransduction, including the light-driven events in a key photoreceptor called cryptochrome. Dr. Melanie O’Neill aims to uncover these events and to describe the mechanism of action of cryptochromes as circadian photoreceptors at the molecular and cellular level. Her research will provide a critical link between light input and biological response, and offer the basis for a description of circadian phototransduction that rivals our detailed description of vision. This research will enable an understanding and potential manipulation of biological timing that may transform our view of human health and our treatment of a host of human diseases including sleeping disorders, depression, and cancer.
Gender and ethnic differences in treatment seeking for acute coronary syndromes
Important advances in the diagnosis and treatment of heart attacks have resulted in a growing majority of people recovering and resuming healthy, active lives following a heart attack. In spite of these medical advances, however, little progress has been made in reducing the time it takes for individuals to seek medical assistance after they first experience symptoms of a heart attack. Many people still arrive at a hospital too late to receive the full benefit of clot-busting therapy and other drugs. Patient-related delays result in a significant number of poor health outcomes and deaths. To achieve better clinical outcomes following a heart attack, people must be able to recognize heart attack symptoms and be willing to seek treatment immediately. Dr. Pamela Ratner is examining the many factors that shape people’s understanding of their risk of heart attack, the symptoms that occur, and the course of action that should be taken. She is focusing specifically on gender and ethnicity, together with other socio-demographic, clinical, psychological, and social factors. Dr. Ratner’s research aims to clarify the roles that gender and ethnicity play in modifying these factors, and to develop a theory of treatment seeking for cardiac symptoms. Results from her research will contribute to designing effective interventions that improve responses and decrease patient-related delays.
Access to care at the end of life: encounters between home care nurses and family caregivers
An important social change of the last quarter century has been a shift in the setting for health care delivery away from institutions — the move from facility-based care to home-based care. In particular, access to palliative home care services has become a major health policy issue in Canada. With an aging population, a growing number of Canadians diagnosed with terminal illness, and almost 90 per cent of Canadians reporting a preference to spend their final days at home, current government policy is pressing for more and better care of the terminally ill in the community. While several conditions are needed to effectively support palliative care at home, two of the most important are the availability of family caregivers (FCGs) and access to services by home care nurses (HCNs). Dr. Kelli Stajduhar is studying the decision-making factors that HCNs take into account when providing specific levels and types of palliative home care nursing services and exploring how the relationships between HCNs and FCGs shape access to care for dying patients. She is interviewing FCGs providing palliative care at home, HCNs and expert clinicians and administrators. Dr. Stajduhar is also observing relationships between HCNs and FCGs to better understand how these interactions affect access to care. Ultimately, results from this research will inform the development of health services, policies and HCNs’ decision making in order to improve access to care for families in palliative care.
Structure-based antibiotic discovery on the bacterial membrane
The growing resistance of bacterial infections to standard antibiotic therapies is a major health concern around the globe. The microorganisms that cause serious illnesses such as hospital staphylococcus aureus infections, tuberculosis and meningitis are increasingly developing antibiotic resistant strains both within the hospital and community settings. Some particular bacterial infections, often termed “”superbugs””, have become entirely resistant to all antibiotics currently used in hospitals. Dr. Natalie Strynadka’s research is directed at understanding the way in which bacteria resist current families of antibiotics and at developing new antibiotic drugs that work by inhibiting specific features of the bacterial life-cycle. Her research team will undertake this research by characterizing the three-dimensional atomic structures of molecules critical to the viability of the bacteria, such as their ability to “inject” antibiotic resistant genes into host cells. By describing these structures in fine detail, they will be positioned to design antibiotics that specifically inhibit these critical molecules of the bacteria, destroying its ability to cause disease.
Role of SPARC in cancer therapy
Colorectal cancer (CRC) is the third most common cancer in both men and women, and was responsible for an estimated 8,300 deaths in 2004 in Canada. While there has been an overall decline in the incidence and mortality of CRC in the past two decades because of better cancer prevention, the overall five-year survival rate continues to be poor. This is due in part to chemotherapy resistance, which is common in many solid tumours. Dr. Isabella Tai’s research is directed at understanding the mechanisms enabling cancer cells to become resistant to cancer drugs and other therapies. Using a high-throughput “genomics” approach, her research team has developed a comprehensive list of genes involved in chemo- and radiotherapy resistance. One such gene, SPARC, had low levels of expression in colorectal cancer cells that were resistant to several chemotherapy agents. By increasing the levels of SPARC in therapy refractory cells, response to radiotherapy and chemotherapy was restored and tumor size reduction was observed. Dr. Tai’s team is now examining the general applicability of SPARC-based therapy in other cancer model systems, how it promotes tumor regression, and whether patients who are likely to become resistant to therapy can be identified based on a potential diagnostic marker. The results of the project could lead to improvements in cancer treatment and potentially provide a diagnostic marker to identify individuals likely to develop chemotherapy resistance.
Improving the treatment of posttraumatic stress disorder: A controlled evaluation of a new behavioural treatment
Posttraumatic stress disorder (PTSD) is a common consequence of life-threatening traumatic events (e.g., road traffic collisions, military combat, criminal victimization). PTSD is a severe anxiety disorder that often follows a chronic course and is associated with significant disablement. Existing PTSD treatments are only moderately effective and research is needed to find interventions that can improve treatment outcome. One potential method of improving treatment outcome for PTSD is by reducing anxiety sensitivity, which is described as a person’s fear of experiencing the physical sensations that result from anxiety (e.g. heart palpitations, dizziness) and their belief that these sensations will have harmful consequences. Anxiety sensitivity is elevated in PTSD and is associated with PTSD symptom severity. Interventions that directly target anxiety sensitivity have the potential to enhance PTSD treatment outcome. Dr. Jaye Wald is conducting the first controlled study to examine the effectiveness of interoceptive exposure therapy (IE) on PTSD. While this behavioural intervention has been shown to be effective in treating anxiety disorders, its ability to improve the outcome of existing PTSD treatments has not yet been investigated. Dr. Wald will use IE to repeatedly expose individuals to feared bodily sensations, with the goal of eventually reducing their anxiety sensitivity. Results of this research will have important practical implications for the mental health care field and for individuals with PTSD by enhancing understanding of this disorder and ultimately improving its treatment.
Notch signaling in Lymphoid Neoplasia
A common theme in cancer is the dysregulation of a normal developmental process that either directly causes cells to grow in an uncontrolled manner, or renders them susceptible to cellular damage that, in turn, leads to uncontrolled growth. One example of this process occurs with a normal cellular gene called Notch, which is inappropriately activated in a large fraction of cases of a certain type of blood cancer called T cell acute lymphoblastic leukemia (T-ALL). During normal development of the immune system, regulated Notch activity is required for formation of mature lymphocytes that protect the body from infection. When activated, Notch promotes the formation of normal T lymphocytes, but if this signal is not turned off in time, these T cells can undergo malignant change and become cancerous. Dr. Andrew Weng is studying the signals that are generated by Notch activation and the context in which these signals are received by the cell. By understanding the role of Notch in cancer development, he hopes to develop methods for manipulating Notch activity to shut down the growth of established cancer cells, and perhaps also to prevent it from occurring in the first place.