Approximately 1,050 new spinal cord injuries occur every year in Canada, primarily in young people. There are currently approximately 40,000 Canadians living with a spinal cord injury (SCI). As a physician and neuroscientist, Dr. Brian Kwon is actively involved in discovering new ways to improve the prognosis of those with SCI. Experimental treatments that have shown tremendous benefits in animal models of spinal cord injury have not translated in human clinical trials. This discrepancy suggests important differences in the biological responses to spinal cord injury between humans and animals. Within minutes of a spinal cord injury occurring, the spinal cord swells at the injury site. This swelling reduces blood flow and oxygen to the spinal cord tissue and can subsequently result in further secondary damage. Dr. Kwon is researching whether draining some of the cerebrospinal fluid (CSF) that surrounds the spinal cord will reduce the pressure on the cord, restoring blood flow and minimizing the risk for secondary damage. In a clinical trial of patients enrolled at Vancouver General Hospital within 48 hours of their SCI, CSF samples will be taken and measured for proteins that regulate inflammation. This biochemical evaluation will offer the first human description of how these inflammatory proteins are expressed following injury, leading to new biomarkers or indicators of injury severity to assist with further research. The expression proteins will be compared with the expression of proteins in animal models to determine differences in response between humans and animals. Ultimately, these insights will assist researchers in developing therapies to improve the lives of patients with spinal cord injuries.
Program: Scholar
Wild-type Huntingtin’s pro-survival function: A potential role in Huntington’s disease pathogenesis and treatment
Huntington's Disease (HD) is an Inherited brain disorder affecting approximately 1 in 10,000 Canadians that causes progressive disability with an inexorable march towards death averaging 18 years after the onset of symptoms. There is currently no cure for HD and no known treatment that affects the age of onset or the progression of symptoms. The underlying genetic defect that causes HD is now known and the mutant HD gene produces an abnormal protein called huntingtin (htt) that damages brain cells. Many research groups around the world are studying how the abnormal htt protein kills cells, but the normal cellular function of htt is not well understood. This proposal is unique in that we will examine the protective role that the normal htt protein may play in the disease process of HD. We previously demonstrated that the normal htt protein has a pro-survival function in the brain and prevents various forms of brain cell death. Our proposed experiments will determine what specific regions of htt are required for this protective role, how protein modifications of htt affect this function, and we will test what effect modulating levels of normal htt have on the progression and development of HD. Based on our preliminary results, I hypothesize that altering the pro-survival function of htt will modulate the process of brain cell injury in HD. Mapping the critical pro-survival regions of htt, investigating the mechanisms by which this function is regulated, and understanding the downstream pathways by which htt modulates brain cell death may provide novel cellular therapeutic targets for HD and for neurodegenerative disorders in general.
The pathways project: Evaluating the transition of psychiatric services from hospital to community
Deinstitutionalization is the process and implementation of the transition of mentally ill individuals to community-based care. Although the rationale for transition from hospital-based to community-based care can be understood in terms of the desire to improve the quality of life of those living with mental disorder, the reality of resettling large numbers of previously institutionalized patients in the community raises questions about the potential risks and benefits for patients, their family members, and the public. Riverview Hospital, once Canada's largest psychiatric hospital, currently cares for the most chronically ill patients in BC, all of whom will be transferred to Tertiary Regional Psychiatric Facilities in the coming years. This significant restructuring of health care delivery provides a rare, naturalistic research opportunity to document the practical, clinical, and social implications of transferring psychiatric services to community-based settings.
Prior to transfer from hospital, Dr. Tonia Nicholls’ team will conduct a detailed evaluation of each patient’s clinical (e.g. physical health, psychiatric symptoms), (b) behavioural (e.g. suicide, self-harm, aggression, activities of daily living), and (c) psychosocial (e.g. consumer satisfaction, quality of life, stigma) status. After moving into a community care setting, each patient will be re-assessed several times to determine what, if any, changes are found. The study will evaluate to what extent closing Riverview Hospital has intended and unintended consequences. Specifically, Dr. Nicholls will study rates of homelessness, criminalization, and the transinstitutionalization experiences and health system utilization (e.g. contacts with police, admissions to correctional and forensic facilities, emergency room visits) of this cohort of individuals with severe mental illness.
In addition to patient interviews, information from patients' family members and peers, as official record databases will also be used in this study. Through a comprehensive evaluation of the process and outcomes of transferring psychiatric care to community settings, her work will demonstrate the implications of deinstitutionalization at both an individual and community level and will serve to inform future practice and policy decisions.
Risk Assessment and Prediction of Infectious Disease Outbreaks (RAPID): An integrated framework of quantitative public health policy design
Traditionally, British Columbia has played an important role in public health policy design in Canada. BC has a reputation for providing leadership in population health research aimed at improving the health of its residents. To continue providing leadership in this realm, BC needs to create a timely, quantitative framework to stifle the increasing threat of emerging and re-emerging infectious diseases. Despite medical advances, communicable diseases remain a major cause of death, disability and social and economic upheaval for millions around the world. Consequently, combating infectious diseases requires planning beyond individual-based interventions. Dr. Babak Pourbohloul is working to develop an integrated research, mentoring, education, and knowledge translation platform. He will create a quantitative risk assessment and predictive framework to understand the pattern of infectious disease spread, and will develop mathematical models to identify optimal, cost-effective control strategies against a wide variety of infections. This research will enable public health leaders to address six key areas: the most effective control strategies for emerging respiratory infectious diseases and influenza pandemic preparedness; vaccination program evaluation; public safety and bioterrorism; public health issues associated with infection control in marginalized populations; hospital infection prevention; and outbreak containment. Through Dr. Pourbohloul’s research, both the province and the BC Centre for Disease Control can maintain their vision and leadership in managing the complexity of infectious disease transmission with innovative and sophisticated quantitative tools – improving the health of all Canadians.
Developing a Decision-Support Framework for Locating Regional Palliative Care Hubs in Rural and Remote Canada
Canada’s aging population is on the rise, resulting in greater demand for palliative care services (PCS). However, service delivery is unable to meet demand, particularly in rural and remote areas due to the absence of existing infrastructure, qualified medical practitioners, funding, and user volume. In addition, many of these services have been developed in urban centres, resulting in a centralization of palliative care services and facilities.
One solution to address the need to provide PCS to residents of rural and remote areas is to relocate care recipients to service-rich urban centres. However, research has documented that most Canadians prefer to spend their last days at home. The development of regional palliative care hubs is an innovative solution for delivering PCS to residents within these rural and remote communities.
Using a mixed-method study design that combines geographic information science (GIS) and spatial analysis with qualitative methods, Dr. Nadine Schuurman will determine which rural and remote BC communities are potential candidates for regional palliative care hubs, and what potential barriers exist for accessing these services — both by patients and by providers. Her research will also include the development of a GIS-based decision support tool for determining the most suitable communities for serving regional centers, and identifying the types of patients and providers most likely to benefit from having a hub in these locations.
Dr. Schuurman’s goal is to provide insight into how to provide palliative care to an aging population in rural and remote Canada and to help inform policy and program decision-making related to the allocation of health care resources.
Genetics of alopecia areata
Alopecia areata (AA) is a common autoimmune disease leading to extensive hair loss in men, women and children. About 640,000 Canadians (one out of 50) will develop AA. There is no cure, and treatment options are minimal. While, in general, the condition is not life threatening, hair loss can be psychologically devastating, particularly for women and children. Using a rat model, Dr. McElwee has identified several areas on chromosomes where genes coding for AA susceptibility are present. Now further work is required to determine the specific genes involved and what they do. Once these genes are identified in the rat model, the next step is a large scale study to identify corresponding genes in AA-affected humans. A more comprehensive understanding of the structure and function of these genes in comparison to corresponding genes in non-affected individuals will lead to a better understanding of how AA develops. In the long run, the goal is to explore the development of treatments which specifically target and ameliorate the affects of underlying genetic flaws that give rise to the disorder.
Novel strategies for treatment of PTEN deficient prostate cancer
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men of the Westernized world. While early stage disease is frequently curable with surgery or radiotherapy, limited treatment options are currently available for approximately one-third of patients who clinically present with locally advanced or metastatic disease resulting in a poor prognosis for patients with advanced disease. One treatment option that is currently being used for advanced PCa is a medical procedures designed to block androgenic steroids to induce death of prostate cancer since prostate cancer cells typically require these hormones for their growth and integrity. While this treatment is often effective with a response rate of up to 80%, within 1-3 years the tumours inevitably recur as hormone-refractory variants, a condition for which there is no current effective therapy. Thus if we are to have an impact on survival rates of patients with PCa, new therapeutic strategies are required for treating advanced disease. Up to 50% of advanced prostate cancers have acquired mutations in a gene called PTEN that essentially inactivated it. Inactivation of PTEN in prostate cancer is correlated with a poor prognosis. Loss or inactivation of this gene makes prostate cancer cells more resistant to different forms of therapy including chemo-, radiation and hormone-therapy. The development and progression of cancer is dependent on the deregulation of the intricate balance in the rates of cell growth and death. The proposed project addresses how loss of the PTEN gene confers cell with a survival advantage and resistance to therapies. Under ordinary conditions, PTEN keeps growth of normal cells in check by serving as a brake to inhibit cell growth. When PTEN is mutated in cancer, the brakes fail and this confers uncontrolled growth and increased resistance of the cancer cells to chemotherapy and hormone ablation therapy. My lab is actively working on how loss of PTEN protects prostate cancer cells from death signals and we are looking for different ways to block the effects of inactivating PTEN. Results of this study will be directly relevant to development of new therapies aimed at treating the subset of advanced prostate cancers that have lost PTEN.
Social Determinants of Rural and Northern Community Health
Research has increasingly linked the health of individuals to the integrity of a community’s social fabric, the extent to which residents in a community trust each other and participate in community activities, and on the networks of communication and exchange between community members. However, little research on this “”social capital”” has been conducted in British Columbia. Yet, communities in British Columbia are facing an accelerated pace of structural change due to the effects of globalization, changes over the past 15 years in health and welfare systems, and industrial restructuring. It is imperative, particularly in the Central and Northern Interior of the province, where an unprecedented eco-economic crisis is unfolding due to the pine-beetle infestation, that the impacts of these changes in community structure and functioning and, in turn, their impacts on social capital and the health and the health and educational status of children and adolescents are investigated in a way that may lead to amelioration. Building on the foundation of over a decade of work on the social determinants of workplace and community health and a recently awarded New Emerging Team grant to investigate the social determinants of community health in British Columbia, this program of research will further methodological developments in community health research while strengthening the base for community health research at the University of Victoria, in BC, nationally, and internationally. Given that many other communities in Canada, as well as in other nations, similar challenges, the knowledge, conclusions, and recommendations arising from this program of research will be applicable in other jurisdictions.
Community screening and intervention for high-risk oral premalignancies
Worldwide there are over 300,000 new cases of oral cancer each year with half of these cases dying of the disease; mainly because of late diagnosis. As such, the advanced widespread disease often requires complex and disfiguring treatment, consequently with a huge impact on the quality of life of the patients, at the same time adding stress to the health care system. It is important to prevent and identify the disease at early stages.
In BC, a particular high-risk medically underserved community resides in Vancouver Downtown Eastside (DTES), the location of one of Canada's poorest neighborhood. Residents in this community are at high risk for oral cancer because many are heavy smokers and regular consumers of alcohol, which are the established risk factors for oral cancers. Further aggravating the problem is that many are having complicated immune status; additionally, poor nutrition and oral hygiene and a limited access to dental and medical care.
There is an urgent need to reach this high-risk population to make sure these individuals are equally served. Moreover, a screening program targeted toward such a high-risk community could effectively decrease the suffering and fatal impact attributable to oral cancer. The key focus of my research is to work within high-risk communities to develop a screening strategy targeted towards the hard-to-reach underserved populations where the need is greatest.
The main objective of this study is to establish current research activity in the study of oral cancer and precancers within the context of community-based clinics in a high-risk population in Vancouver. The activities involve: 1) to establish the first oral cancer screening clinic in a high-risk community in BC, 2) to incorporate and evaluate several new visualization tools and molecular markers for the identification of high-risk OPL and early cancer, and 3) to understand the biology of infection and inflammation to OPLs and its role in cancer formation in a high risk community. This work meets the main objectives of the National Cancer Agency, Canada in prevention and early detection of cancers.
Detection of novel microdeletions and microduplications in persons with intellectual disability using whole genome microarrays
Intellectual disability (ID) is a diagnosis given to persons who have life-long cognitive and adaptive impairments that commence in early life. ID affects about 1-3% of the population, thus nearly 1 million Canadians have an ID. The cause of ID is unknown in at least 40% of all cases. Recent reports have suggested that very tiny chromosome changes are the cause of many cases of ID. These tiny chromosome anomalies are usually not seen using routine microscopic analysis. However, recently developed microarray technology provides an opportunity to detect these very small changes.
Dr. Evica Rajcan-Separovic has used this technology to look for such abnormalities in 200 subjects with ID and have detected very small genetic changes in 16% cases. Some of the genetic abnormalities were seen in more than one individual. Her team plans to extend their array study to 400 more ID individuals in the next 6 years and to examine using molecular methods another 2000 subjects with ID to see if they can find additional individuals with the same abnormalities. By studying a larger number of individuals with the same chromosome change, they will be able to determine what physical features and medical issues are due to that genetic change.
Rajcan-Separovic's next step will be to develop Health Care Watches for each new condition identified. These will describe expected health issues, so that families and physicians can be better prepared to care for individuals with these new genetic syndromes. This approach will eliminate costly multiple testing and searching for answers, and should allow optimal care and health for persons with ID.