Neurological diseases and disorders have been estimated to affect 3.6 million Canadians living in the community and over 170,000 Canadians living in long-term care facilities, including in British Columbia. However, we have limited information about the molecular mechanisms that cause many of those neurological conditions, largely because of the complexity of our nervous system. Therefore, understanding the mechanical processes that impart precise neural circuit formation using a simple model organism is critical to try to find ways to prevent neurological diseases and cure patients.
Toward this goal, Dr. Mizumoto will use nematode Caenorhabditis elegans as a model system to investigate the mechanisms that underlie neuronal circuit development. C. elegans has a short life cycle (3 days/generation) with a simple nervous system consisting of only 302 neurons, making it a great genetic model system to study the fine neural circuit formation. Most importantly, countless studies have shown that mechanisms and molecular machineries underlying the development of the nervous system are remarkably conserved between C. elegans and humans. It is likely that the knowledge obtained from our research will be directly applicable to the human nervous system and to diseases associated with nervous system defects.
Using C. elegans, Dr. Mizumoto will explore how neurons communicate with their neighboring neurons/cells to form a stereotyped neuronal pattern at the level of single synapse, which is a specialized interface between neurons or between neurons and other type of cells (such as muscle cells), to transmit electrical signals. Using a combination of C. elegans genetics, molecular biology and microscopy, this research will move towards an understanding of the fundamental principles of neural network formation.These studies will advance health-related knowledge by providing direct targets for other researchers to test in fruit fly (Drosophila) and mammalian models of neurodevelopmental disorders affected by Sema/Plexin signaling and others, and ultimately the development of therapeutic strategies for the treatment of these disorders.
End of Award Update: April 2023
Most exciting outputs
Many of the genes that we discovered from our research in specifying synapse formation are heavily associated with various neurological conditions, which suggest that our work may have potential to better understand the disease conditions affected by mutations in these genes.
Impact so far
As our work is fundamental and basic, we do not expect the impact of our work to be immediate.
Potential influence
We hope that our discoveries would lead to the development of therapeutics to treat neurological conditions in 20 years.
Next steps
We will continue to uncover the fundamental mechanisms of synapse pattern formation and specificity using C. elegans as a model organism.
The rising incidence of type 2 diabetes (T2D) puts financial stress on health care systems in British Columbia and across the world. Lifestyle interventions can improve cardiometabolic health to prevent or treat T2D, but optimal lifestyle strategies (e.g. exercise intensity, type, timing; diet composition) are not well-defined and adherence is notoriously poor.
The goals of Dr. Little's research are to optimize lifestyle interventions for improving cardiometabolic outcomes and uncover potential mechanisms underlying these health benefits. The research program aims to improve cardiometabolic health and reduce inflammation via a series of translational studies to define the optimal exercise and diet strategies and uncover cellular mechanisms underlying the benefits. To translate findings for true health impact, YMCA has partnered to implement an HIIT walking intervention in the community. In addition, a randomized controlled trial will be implemented to evaluate the effectiveness of a pharmacist-led intervention, implemented through a network of 13 BC pharmacies, to teach patients with T2D how to follow a low-carb, high-fat (LCHF) diet while also reducing their medications. This has tremendous potential to change diabetes management in BC through an innovative pharmacist-led therapeutic nutrition program using LCHF diets.
The long-term goals of this research will be to develop optimal evidence-based exercise and diet interventions that improve patient health and inform clinical practice guidelines for the prevention and treatment of T2D. Elucidation of the cellular and molecular mechanisms underlying the anti-inflammatory effects of exercise and diet approaches will also be used to define the best anti-inflammatory lifestyle interventions, and identify potential therapeutic targets for prevention and treatment of T2D.
Among women who give birth in industrialized countries maternal age, obesity, twin or triplet pregnancy, and presence of chronic diseases such as diabetes and hypertension continue to increase. For example, 34% of mothers in Canada today are overweight or obese, and approximately 20% of births are to women over 34 years. These demographic trends highlight the need for increasingly complex obstetric care with careful prenatal monitoring and timely obstetric intervention if necessary.
Dr. Lisonkova's research will quantify the risk of severe maternal morbidity by developing a score system that will accurately distinguish between high, moderate, and low risk women. This score calculator will help, for example, women in rural areas to decide about transport to higher-level obstetric care, as these women may face geographical barriers to timely transfer. Determinants of these elevated risks will be examined, as well as whether these risks increase with distance to maternity care, seasonally (for example in winter), or occur only among women in selected geographically specific areas.
The results of this research will provide information to women who are contemplating delaying childbirth, who are overweight or obese, or have chronic health problems. This information will also help health care providers in pre-pregnancy and pregnancy counselling, and health care administrators to identify maternal care needs with respect to maternal-fetal medicine specialists and intensive care units. The maternal morbidity risk score calculator can also be used to adjust for baseline risks (maternal comorbidity, etc.) when comparing hospital performance and evaluating new safety measures in maternal care.
This project will be conducted in collaboration with the Society of Obstetricians and Gynaecologists of Canada, Public Health Agency of Canada, and the Department of Family Medicine & Midwifery, University of British Columbia. The collaboration between midwifery, family physicians and obstetricians will be beneficial especially for women in rural areas, for whom accurate risk identification is crucial.
New HIV diagnoses are 71 times higher among gay, bisexual and other men who have sex with men (GBM) than other men in Canada. Since 2010, BC has adopted Treatment as Prevention (TasP) as a policy to increase HIV testing and engage more HIV-positive individuals in effective treatment to reduce transmission at a population level. However, the number of new diagnoses among GBM in BC has remained largely unchanged. Further, surveillance shows an increase of HIV diagnoses among the youngest birth cohorts of GBM. HIV pre-exposure prophylaxis (PrEP) is a new preventive tool for HIV-negative GBM, but inaccurate information, sub-optimal adherence or risk-compensation could result in a false sense of security, paradoxically leading to increased HIV transmission. In addition to HIV, infectious syphilis is now epidemic among GBM in BC.
This research program will address the HIV and sexually transmitted infection (STI) epidemics among GBM in Metro Vancouver and BC. Dr. Lachowsky will measure HIV risk behaviour over time, determine how PrEP affects bacterial STI incidence, and analyze shifting attitudes about HIV, challenges with HIV prevention and treatment, and changes in sexual negotiation and practices. Results will directly inform population-specific, age-relevant public health policy, programming, and interventions to reduce the burden of HIV for GBM, especially young GBM.
Dr. Lachowsky will employ a bidirectional, integrated knowledge translation approach, with a Community Engagement Committee and key academic, public health, and community partners. An interactive Web 2.0 hub will allow for knowledge dissemination and generation with community and service providers, and will be complemented with more traditional presentations, workshops, and publications.This single research project is part of a larger program of research examining health disparities amongst GBM in BC and Canada using interdisciplinary, community-based approaches.
British Columbia is currently in the process of developing and implementing new evidence-based policies and clinical reforms to address problematic substance use, including new: (i) pharmacotherapy approaches (e.g., replacement therapies); (ii) clinical practice guidelines; and (iii) integrated service delivery models of care. While men who have sex with men (MSM) represent a key group with historically high levels of substance use disorder and subsequent social and health-related sequelae (e.g., increased rates of HIV and sexually transmitted and blood-borne infections), there remains a gap in our knowledge about how best to design and implement services for today's generations of various sub-groups of MSM who use drugs (e.g., MSM who are: young; Indigenous; economically deprived).
Dr. Knight's five-year population health research program will adapt health policy and service delivery practices to improve substance use treatment trajectories for key groups of MSM who use drugs and are at risk for severe health and/or social consequences (i.e., the criteria for substance use disorder, as defined under DSM-V criteria). The aim will be to identify the most efficacious and scalable combinations of strategies to adapt interventions that respond to MSM's individual needs and broader social and structural conditions. This approach to implementation science offers a way to go beyond describing the problem and to focus on building an evidence base for implementing and adapting context-sensitive and population-specific solutions into routine policy and practice.
With collaborators representing the BC Ministry of Health, Vancouver Coastal Health, BC Centre for Disease Control and YouthCO HIV/Hep C Society and the BC Centre for Excellence in HIV/AIDS, as well as through the engagement of the BC Centre on Substance Use's Community Advisory Board, Dr. Knight's findings will be used to inform the development of policies (including clinical and provincial guidelines) to effectively scale up and integrate services that have the capacity to improve substance use treatment trajectories for MSM. Contributions to new knowledge will include the identification of the individual, social and structural factors shaping MSM's ability to reduce problematic drug use and prevent severe health and social outcomes (e.g., HIV and/or Hep C). Study outputs will also be assessed at an annual Stakeholder Workshop in which recommendations will be developed and refined for clinical and provincial guidelines.
British Columbia (BC) faces a mental health and addiction crisis with an estimated cost of $100 million annually. In April 2016, a public health emergency was declared due to an alarming increase in opioid-related overdose deaths in recent years.
People who use illicit drugs (PWUD) bear a great burden of preventable morbidity and mortality from drug overdoses as well as other comorbidities including mental disorders and infectious diseases. While opioid agonist therapies (OAT) have proven effective in reducing heroin use, concomitant use of opioids and stimulant drugs (e.g., heroin and cocaine) is common among PWUD. Furthermore, recent research has suggested that many PWUD also suffer from untreated chronic pain, which may be driving prescription opioid (PO) misuse among this population. However, little is known about patterns of concomitant use of illicit opioids, POs and stimulants, and how OAT and other health services may serve to mitigate potential harms associated with such polydrug use. Currently, no approved pharmacotherapies exist for stimulant use disorder, necessitating urgent research effort in this area.
Dr. Hayashi's research will inform policies, programs and clinical practice to reduce harms associated with polydrug use. The primary research objectives are:
- To investigate and address the impact of PO misuse, untreated chronic pain and concomitant opioid and stimulant use on patterns of drug-related harm.
- Evaluate "naturally occurring" interventions and policy changes (i.e., new opioid addiction-related services and Vancouver Coastal Health's Downtown Eastside Second Generation Strategy) that are relevant to polydrug users.
- Evaluate the efficacy of a novel pharmacotherapy to treat polydrug users.
The research will employ vast longitudinal behavioural and biological data collected since 1996 via three ongoing prospective cohort studies of over 3000 PWUD in Vancouver. The findings are expected to inform care development and overdose prevention efforts for a high needs population in BC. One objective will involve implementing a clinical trial to evaluate whether an amphetamine-based medication reduces powder/crack cocaine use among 130 patients on OAT, who have both opioid and cocaine use disorders. If the study medication proves effective, Dr. Hayashi's research will potentially contribute to the identification of the first proven medication for cocaine addiction.
Concerns about the sustainability of publicly funded health systems and the rising cost of care abound, yet there is little research that explores health care efficiency. Simple cost-saving exercises (i.e. cutting services) may risk harming patients, while more sophisticated, efficiency-saving approaches aim to provide health care at a greater benefit per unit of cost. Encouraging quality and value of health care delivery, whilst reducing waste, is also an indirect way to control health care costs. Undertreatment (failure to use best available care), overtreatment (treatment contrary to best-available evidence or preferences of patients), and poor coordination of care are three key clinical sources of waste. Many large-scale schemes aim to incentivize better health care, but show mixed results.
Dr. Harrison’s research will translate aspects of successful schemes and inform sustainable health care provision in Canada, focusing on musculoskeletal (MSK) diseases as they have been central to successful schemes. MSK diseases affect 11 million Canadians, and contribute hugely to the economic burden of disease in Canada. They have extensive impacts on people’s lives, including their health-related quality of life, ability to work, financial situation and reliance on the health care system. Additionally, high quality care of rheumatic disease requires early access to treatments which are often complex and considerably different from one another. Therefore, it is increasingly recognized that patients need coordinated, multidisciplinary support and care.
Dr. Harrison’s program will encompass policy-focused health economics and outcomes research to inform the design of financial and non-financial incentives to improve the efficiency of health care delivery.
End of Award Update: September 2022
Most exciting outputs
The project allowed me to explore whether a change to introduce a billing code for multidisciplinary care in rheumatology changed the experience of patients visiting rheumatologists in BC. We found that rheumatologists who used multidisciplinary care were able to expand services for patients.
Impacts so far
Our work adds to the evidence around incentives for multidisciplinary care in chronic disease. This will help inform future policy decisions.
Next steps
I continue to work on the evaluation of incentives and changes in policy for health care. I am currently co-leading a project evaluating the biosimilars initiative in BC.
Useful links
Findings from health promotion research that could help Canadians live healthy lifestyles are often not applied in practice. This gap between health promotion research and health promotion practice is particularly concerning for people with spinal cord injury (SCI). Despite people with SCI's urgent need for interventions that respect their unique challenges and barriers to health behaviour change, there are very few health promotion interventions designed for people with SCI. To ensure health promotion research improves the health of all Canadians, there is an urgent need to improve the use of health promotion research in practice.
The aim of this five-year knowledge translation research program is to examine methods for improving the use of health promotion research in real-world practice. Given the lack of health promotion interventions for people with SCI, this research program will examine how we can improve the use of health promotion evidence to enhance the health of people living with SCI.
Dr. Gainforth will examine how successful and unsuccessful practitioners apply health promotion techniques when promoting healthy behaviours to people with SCI and develop the first evidence-based guidelines, tools and interventions to improve knowledge translation partnerships between researchers and members of the SCI community. Lessons learned from practitioners will be used to develop and test tools and interventions to help other practitioners successfully promote healthy behaviours to people with SCI.
Ultimately, this research will develop best practices for building capacity among researchers and community members to conduct and share research in partnership. In turn, findings and the approach can support other research teams aiming to use partnerships to conduct and share research that enhances the health of marginalized groups.
Previous research by Dr. Foster has illustrated that angiotensin receptor blockade can abolish the blood pressure response to intermittent hypoxia (IH), reduce oxidative stress and increase nitric oxide bioavailability. In addition, recent work suggests heightened peripheral neurovascular transduction in response to baroreflex activation.
Building on this work, over the next 5 years Dr. Foster will focus on the cardiovascular consequences of IH associated with obstructive sleep apnea (OSA). Since OSA and IH directly contribute to the morbidity and mortality of hypertension, myocardial infarction and stroke, there is an urgent need to establish a treatment capable of protecting OSA patients from IH-induced cardiovascular disease (CVD).
Dr. Foster's research will elucidate the mechanisms by which AT1R antagonists or statins could protect OSA patients from IH-induced CVD. By breaking the link between CVD and OSA, and capitalizing on the pleiotropic properties of angiotensin receptor blockers and statins, this research is ultimately intended to generate a novel treatment. This knowledge will provide the necessary proof of concept for large-scale clinical trials, and will help reduce stress on health care infrastructure and improve the health, quality of life and longevity of Canadians.
Addiction treatment is critical to addressing the tremendous health and social harms experienced by street-involved youth (SY) with substance use disorders (SUD), including the current fentanyl overdose crisis. To date, the addiction treatment and recovery landscape in British Columbia (BC) reflects a mix of regulated, publicly funded programs (e.g., methadone and Suboxone programs, residential detoxification and treatment programs), as well as unregulated privately and publicly funded programs (e.g., informal recovery houses, Twelve Step programs) that span acute and community healthcare settings. Sustained drug use cessation is an important goal of these programs. However, it is recognized that for many youth their addiction treatment trajectories include periods of engagement, dis-engagement, and re-engagement with various programs, as they move in and out of periods of relapse, increases and reductions in drug use, and drug use cessation. The recovery trajectories of youth who remain largely outside of healthcare settings are also often characterized by this kind of dynamic process.
Dr. Fast will examine and inform ongoing efforts in the Lower Mainland to create a more comprehensive and coordinated system of addiction services for youth, and generate new knowledge to optimize the integration of evidence based addiction treatment across the acute and community healthcare settings accessed by SY. Integrating the methods and perspectives of medical anthropology and implementation science she will advance understandings of how individual, interpersonal, organizational, and structural factors operating in, but also across, acute and community health care settings in the Lower Mainland shape the delivery, uptake, and outcomes of youth addiction treatment interventions.
A nuanced, ethnographic understanding of these places and contexts will inform policy and practice recommendations to improve the addiction services system for adolescents and young adults so that it meets the needs of SY, pursuant to the goal of addressing SUD and the overdose crisis among this population. Dr. Fast will employ innovative and participatory arts-based methods to generate and disseminate policy and practice recommendations that align with the complex realities and everyday lived experiences of SY.
