Health Innovation Design and Evaluation Research Team

In their ongoing efforts to improve health outcomes, decrease health care costs, and increase administrative efficiency, health care agencies are increasingly investing in information-based technologies (IT). Recently, the Canadian government highlighted the need for developing new methods for evaluating new health sector technologies in order to provide insight into the challenges associated with increased use of IT in health care settings. This award supports the development of a team that is researching the use of IT for epidemiological data collection (EDC), also known as e-epidemiology. The team’s goals include: identifying technological, organizational, governance and implementation challenges associated with the increased use of IT for EDC; addressing data quality issues arising from increased use of IT for EDC; and improving collaborations among researchers, decision makers and technology developers across disciplines who share an interest in e-epidemiology. The team hopes to improve the quality of evidence used in decision making about information technologies used for collecting epidemiological data in BC.

Production of high-quality proteins in plants for screening and treatment of human lysosomal storage diseases

Lysosomes are structures that digest materials within the cell. Lysosomal storage diseases are devastating diseases caused by deficiencies of specific enzymes within the lysosomes. Mucopolysaccharidosis I (MPS I) is a progressive lysosomal storage disease that affects most organ systems. In severely affected humans, this genetic disease leads to early death because of profound disturbances to the heart, brain and other organ systems. One way to correct lysosomal enzyme deficiency is through using purified enzymes for enzyme replacement therapies (ERT). However, the current methods used to commercially produce the enzymes for ERT are prohibitively costly. Because of this, sustained financial support for ERT among affected Canadians is uncertain. Dr. Allison Kermode is exploring whether using plants as hosts to produce these human enzymes will offer a more economical way to provide ERT treatments for MPS I, as well as for Gaucher disease, another lysosomal storage disease. She will test whether plant-made human enzymes are effective as ERTs. She will also establish a plant-based system for assessing potential small molecule treatments for these diseases. Finally, in collaborative work, Kermode will test plant-made lysosomal enzymes in assays for newborn screening of lysosomal storage diseases. Some of the research will be expanded to other therapeutic proteins relevant to Type I diabetes, providing a general platform for plant production of therapeutic proteins.

Structural dynamics of hERG potassium channel gating studied using voltage clamp fluorimetry

Ion channels are cardiac membrane proteins that control the flow of ions like sodium and potassium in and out of heart cells, regulating both cardiac electrical impulses and the contractions associated with the heart beating. Voltage-gated potassium channels, such as the human ether-a-go-go related gene (hERG). are a class of ion channels that open and close – an action known as gating – in response to changes in the electrical potential across the cell’s plasma membrane. In the heart, hERG channels play a crucial role in regulating heart rate and rhythm. Reduced hERG channel function has been associated with loss of the normal heart rhythm and sudden cardiac death. The unique role played by hERG channels in the heart is a result of their unusual gating properties. However, there is limited knowledge about the molecular mechanisms of these gating processes and how they are modulated.

Dr. Tom Claydon is using a new fluorescence technique that he established as a post doctoral fellow that provides a real-time analysis of the protein motions that cause hERG channels to open and close. With a small fluorescent probe attached directly to the channel protein, Claydon’s team can directly study movements that occur within the channel as it opens and closes and measure the electrical current passing through the channel during this activity. Only a handful of researchers worldwide are currently using fluorescence experiments to study ion channel gating. These experiments will provide a comprehensive and unparalleled view of hERG channel function and how it is modulated in health and disease. An understanding of these processes will lay the foundation for new therapies for cardiovascular disease.

Improving Sensitivity of Early Detection of Alzheimer’s Disease via Multidimensional Analysis of Longitudinal Magnetic Resonance Scans

Statistics show that two per cent of Canadians aged 60-74 years, and one-third over the age of 85, suffer from Alzheimer's disease and related dementias. By 2031, more than 750,000 Canadians are expected to have Alzheimer's disease and related dementias. The social and financial costs of managing people with these conditions is significant and puts a severe strain on families and on the health system. Sadly, by the time Alzheimer’s symptoms are recognized and confirmed, there is often substantial irreversible neurodegenerative damage. Current methods of diagnosing Alzheimer’s disease are frustratingly inexact. Lacking ways to identify the onset of disease within the brain itself, clinicians instead look for telltale symptoms, such as failing memory. Even when the disease has progressed and structural changes become apparent on magnetic resonance imaging (MRI) scans, neurologists do not have tools to precisely measure how advanced the disease is, relying instead on visual inspection. Dr. Faisal Beg is trained in engineering, biology and mathematics. Drawing from international MRI databases containing the brain scans of hundreds of older adults with and without Alzheimer’s, he is taking precise measurements to pinpoint where and how brain structures change with the onset of the disease. It’s a complex analysis, made even more challenging due to the normal variations seen in brain shape, size and structure. Beg anticipates that his research will help take the guesswork out of diagnosing Alzheimer’s disease, especially in its early stages. In the longer term, it also may contribute to more accurate assessments of whether new Alzheimer’s drugs are effective in slowing or halting progression of the disease

Multimodal Imaging Instrumentation for Non-Invasive Functional Retinal Imaging

With an aging population comes an increase in a number of diseases and conditions of the eye. A recent advance in imaging – called optical coherence tomography (OCT) – provides a non-invasive way to create high resolution, cross-sectional images of inside the eye. OCT is particularly useful in providing these images of the retina, showing cross sectional images of the various layers with resolution equivalent to a low-power microscope and better than other imaging techniques such as magnetic resonance imaging (MRI).

A new technological development called Fourier Domain (FD) OCT provides these images much more quickly than existing systems. It has also been successful in creating three-dimensional images of the retina, which were previously not possible to obtain. However, clinical use of FD OCT is limited as it generates only an image of the eye’s structures, without providing any functional information about the biological processes at play.

Dr. Marinko Sarunic’s research builds on earlier work where he successfully combined FD OCT imaging with molecular contrast capabilities to provide functional information. He is now using this technology to determine its usefulness in retinal diagnostics, the study of disease processes, and the testing of new drugs and therapies. Development of FD OCT imaging techniques will help physicians better understand and manage ophthalmic conditions, through high resolution visualization and improved minimally-invasive, image-guided procedures.

Total Synthesis and Structure-Activity Studies of a New Anti-Cancer Drug Based on the Natural Product, Imbricatine

With an estimated 159,900 new cancer cases and 72,200 deaths from cancer predicted to occur this year alone in Canada, the need for new cancer therapies with unique mechanisms of action is urgent. Researchers are finding a promising resource among the ocean’s estimated one to two million structurally diverse microbial species. Compounds derived from marine organisms offer great potential in the fight against cancer; in the past decade, more than 30 natural products from the ocean have entered preclinical and clinical trials as potential treatments for cancer. However, it is often not ecologically or economically feasible to extract the active ingredient by harvesting natural sources in the ocean. Synthetic organic chemistry – where molecules are engineered in the laboratory – serves as an alternative source of these compounds. Inhee Cho is focusing on the synthesis of imbricatine, a chemical originally isolated from the Pacific sea star that shows significant anti-tumour properties. The structural core of imbricatine includes tetrahydroisoquinoline, a molecular structure that is also found in many biologically active agents, including anti-tumour antibiotics and drugs that treat diseases such as asthma, Parkinson’s and other nervous system diseases. Cho is developing an efficient way to synthesize tetrahydroisoquinoine, allowing rapid access to this important class of natural products in order to obtain enough material for biological testing and chemotherapy. Cho’s work may facilitate the discovery of new lead compounds with useful pharmacological properties, potentially leading to new therapies for treating cancer

Trajectories towards self-harm, suicide, and other maladaptive coping behaviours

Borderline personality disorder is a serious mental health problem characterized by heightened emotional vulnerability and difficulty modulating emotional responses. Individuals with BPD have high rates of health risk behaviours, such as suicide attempts (75 per cent), self-harm (69-80 per cent), and substance abuse (60 per cent). Despite frequent intense emotional reactions to stressful events, people with BPD lack the skills to reduce their distress through adaptive coping methods. In an effort to reduce these unpleasant emotions and feel better, persons with BPD features often resort to maladaptive coping strategies that are quick and easy to execute (e.g., self-harm, substance abuse) but have negative long-term consequences. However, not everyone with BPD engages in these risky behaviours in response to every stressor, and the specific triggers for these behaviours are largely unknown. Certain types of emotional states (e.g., shame) and life stressors (e.g., being rejected) may be particularly linked with self-destructive coping behaviours. Kristy Walters is examining the specific negative emotions or particular stressful triggers that may be strongly associated with maladaptive behaviours such as self-harm, substance abuse, or suicide. This research will also examine whether or not these relationships among emotions, stressors, and maladaptive behaviours is unique among individuals with borderline personality disorder (BPD). A better understanding of which specific emotions constitute cause for concern, or which types of negative events are more likely to result in self-destructive behaviour, will considerably improve clinicians’ ability to evaluate their client’s level of risk and better identify those clients who are in urgent need of life-saving interventions.

Integrating gene expression data, interaction network information and evolutionary analysis to investigate mammalian innate immunity at the systems level

The immune response is the set of defenses our bodies mount to counter harmful microbes. The innate immune response is our first line of defense, providing protection until the adaptive immune response is activated. Unfortunately, the innate immune response can also be a double-edged sword. It can spin out of control and cause an overwhelming immune response called sepsis, which is responsible for 200,000 deaths every year in the US. The innate immune response is initiated and regulated by complex signalling pathways of genes in our cells. These pathways identify which type of microbe is invading (bacteria or viruses, for example) and mounts appropriate responses. Dr. David Lynn is investigating the genes involved in the innate immune response, how they are turned on and off in particular infections, and what goes wrong in cases of sepsis. This work generates vast quantities of data, requiring computer-based approaches (bioinformatics) to understand and handle such large datasets. Lynn’s work integrates gene expression data with information about how genes and proteins are interconnected in our cells in signalling networks or pathways – providing new information about gene interconnections influence their regulation. He is also investigating the same networks and pathways in other species such as mouse and cow, determining the differences and similarities in their innate immune response. Lynn’s work will help identify potential therapeutic or drug targets that could help safely boost the immune response. It will also highlight cases where important immunological differences make animal models unsuitable for research on human immunity.

Redefining community resilience: community perspectives on the intersection of gender, mental health and adaptive capacity in the context of the Mountain Pine Beetle disaster

Much of British Columbia’s forests have been infested with the mountain pine beetle (MPB), an epidemic that is predicted to result in the loss of more than 80 per cent of the province’s pine forests by 2013. The MPB is also expected to result in the widespread loss of jobs, shifts in traditional resource cultures of affected communities, and an increased risk of forest fires and other natural disasters (e.g. slides, flooding). Gender is recognized as one of the most critical determinants of disaster-related vulnerability. Women and children are disproportionately affected by disasters, reporting higher rates of stress-related health problems (e.g., post-traumatic stress, anxiety, depression), an increased risk of sexual and domestic violence, greater economic marginalization, and substantial increases in their work. They are also less likely to be involved in community-based planning and decision-making processes. Dr. Robin Cox is analyzing individual and collective stressors associated with MPB in four forestry-dependent communities: Barriere/Louis Creek, Clearwater, Quesnel and Wells. She is piloting a community-based research strategy intended to engage affected residents in each community in a series of workshops and focus group interviews. The focus of these events is to identify and elaborate community-based definitions and strategies of resilience that reflect the specific cultural, social, and political contexts of participants. The proposed study will contribute to the development of knowledge around community resilience that integrates a gender perspective, and will lead to the development of policies and procedures that are relevant and responsive to different communities affected by MPB.

New Perspectives on Gender, Diversity, and Health Policy, Planning, and Services

The primary methods for identifying and responding to differences between men and women in the health context are gender-based and gender-sex-based analyses (GBA/GSBA). While these approaches are intended to consider diversity within each group, they do not always capture how gender interacts with other factors such as race/ethnicity, socio-economic status, sexual orientation, geography, ability and age. Not taking these factors into account in health planning, implementation and research can result in real economic and human costs for health care consumers. These include lost opportunities, ill health, suffering and perhaps overall, an ineffective and inequitable health care system. A key challenge facing researchers and policy makers is how to move beyond singular variables (e.g. gender) to understand the complex dynamics at play between gender and health. Dr. Olena Hankivsky is examining how GBA and GSBA are applied in health planning, services and policy in Canada, Sweden, the UK, Australia and the Ukraine. She is exploring innovative improvements for analyzing gender and diversity in a health context. In particular, Hankivsky is conducting a gender and diversity analysis of the most recent health reform initiative in British Columbia — The Conversation on Health. The findings could contribute to developing policy tools and interventions that will improve the effectiveness and efficiency of health services and programs for vulnerable and marginalized populations in BC, Canada, and internationally.