Lungs are constantly exposed to environmental challenges, making them susceptible to infection and injury. For this reason, they are protected by specialized cells that can respond rapidly to danger signals. Amongst these cells are innate lymphoid cells (ILCs) that include three main subsets: group 1, group 2 and group 3 ILCs. To date, the majority of the studies have focused on ILC2s and their importance in allergy and tissue repair. However, it is now becoming evident that ILC3s play a key role in lung health. In fact, ILC3s have recently been shown to accumulate in the lung after Mycobacterium tuberculosis infection and in an obesity-induced asthma disease. Accordingly, preliminary results show that the accumulation of ILC3s in the lung is mediated by IL-1b, yet the mechanisms inducing ILC3s in the lung and their function remain unclear. This project will provide an extensive analysis of the origin and functions of ILC3s in naive and inflamed lungs, with an ultimate goal of translating our findings to a wide range of lung diseases, which are life-limiting and still a major cause of death in young, elderly, immune-compromised and cystic fibrosis patients.
Research Location: University of British Columbia - Vancouver Campus
Using population-level administrative data to study the health of youth with developmental disabilities transitioning to adult services
There is evidence in North America that people who have a developmental disability (DD) are living longer due to improved health care for high risk babies and children and to increases in longevity in general. However, in BC there is nothing known about the lifespan, health and health care usage of these individuals. The health of people who have a DD as they transition from child health care services (often pediatricians) to adult health care services (often family physicians) may be of particular concern. Pediatric services may offer more specialized knowledge and longer appointments which support the health of people with complex medical conditions. This specialized support may no longer be available as people with a DD transition to adulthood.
This study will use population- level administrative health data from Population Data BC to examine health care usage of people with a DD who are transitioning from child to adult health care services. Information gained from this study will be used to increase understanding of current health care needs and planning for future health care for this vulnerable population.
Understanding and disrupting fear memory in the brain
Fear memory, like that occurring in post-traumatic stress disorder, imposes pronounced health and financial burdens. Our laboratory seeks to understand and therapeutically disrupt the neurobiological elements of fear memory.
To do this, we take a multidisciplinary approach that combines cutting-edge experimental and computational techniques. To begin, in mice that have obtained fear memory in a laboratory setting, we measure the expression of every gene in the mouse genome for thousands of individual brain neurons. From these Big Data, we identify genes and neuron types that participate in fear memory. Using genetic and pharmacologic approaches, we manipulate these genes and neuron types with the aim of disrupting fear memory in a safe, acute, and precise way.
The results of this research will provide a comprehensive understanding of the basic biology of memory, help to innovate novel targets and approaches for disrupting fear memory, and generate a framework with which other anxiety and memory disorders may be interpreted. In the long term, we aim for these results to guide the generation of new therapeutic approaches for preventing traumatic fear memory in humans.
Preventing Osteoarthritis after a Sport-related Knee Injury
By 2040, 25% of Canadians will have osteoarthritis (OA), a disabling joint disease. This number will be as high as 50% for those who hurt their knee playing youth sport. Currently, the treatment of youth sport knee injuries focuses on return to sport. Few seek care beyond their injury, and little effort is made to prevent OA. Stop OsteoARthritis (SOAR) is a new physiotherapy program to reduce the risk of OA after a youth sport knee injury.
Designed with a team of patients, clinicians and researchers, SOAR teaches active youth how to manage their OA risk, and improve knee muscle strength and physical activity levels after injury. SOAR consists of a knee camp, personalized exercises, wrist-worn activity-tracker and weekly counselling.
This research will assess what youth with a sport knee injury think about SOAR and how well SOAR works to reduce muscle weakness and inactivity – proven risk factors for knee OA. We will also explore new ways to monitor knee health after injury.
The SOAR team will continue to include patient and clinician partners to make sure that SOAR is practical, and relevant. It is expected that SOAR will improve the health of young British Columbians who have a sport knee injury and reduce their risk for OA.
Stress resilience across the adult lifespan: Linking dynamic day-to-day protective factors to aging and health
Canada is experiencing an unprecedented demographic shift with the aging of the population. Older adults face major stressors and life transitions (e.g., retirement, bereavement, caregiving), in addition to accumulated biological wear-and-tear due to a lifetime of exposure to stress.
Yet, the impacts of stress vary between people and across situations. It is therefore important to identify protective factors that may promote more adaptive stress responses, particularly in midlife and late adulthood when risks increase for aging-related diseases.
The proposed program of research will focus on stress resilience factors in daily life (positive events and sleep) that may mitigate the impacts of stress on health and aging. Research studies will examine the stress-buffering effects of daily positive events and sleep, positive events as protective factors for aging and health disparities, and the development of a mobile intervention to cope with stress as it unfolds.
This research will contribute to a better understanding of stress resilience and health in the context of adult development and aging. Findings will inform strategies to reduce stress-related health conditions and to promote optimal aging among Canadians.
Characterizing the Psychological and Social Predictors of Increased Preventive Service Use
In the next 20 years, the percentage of adults aged ≥65 in Canada is projected to increase by nearly 60%, and among all Provinces British Columbia is aging the fastest. As our population ages, identifying factors that foster healthy aging is crucial for improving the health of older adults, and containing healthcare costs. One way to cultivate healthy aging is by increasing preventive service use (e.g., flu shots, screening for chronic conditions). Yet, <50% of adults aged ≥65 are up-to-date with them.
Thus, a central challenge is to identify modifiable factors that increase their use. The objective of this proposal is to identify key psychosocial well-being factors that are associated with increased preventive service use and begin piloting interventions. Building on prior work, the central hypothesis is that several hypothesized psychosocial well-being factors are associated with increased use of preventive services.
Regarding outcomes, this research is expected to have knowledge translation value as study results will identify psychosocial factors that might emerge as novel targets for interventions aiming to increase preventive service use; further, we will pilot test scalable interventions that target identified factors.
Technology for image-based screening to enhance protein production
New medicines being developed to treat complex diseases, such as cancer, multiple sclerosis, and rheumatoid arthritis are increasingly becoming large and complex molecules, such as proteins. These molecules must be produced using cells grown in a laboratory or production facility. A key bottleneck in the development of such new medicines is producing sufficient quantities of these molecules for various stages of rigorous testing to ensure safety and efficacy. This project will develop a technology to generate better producer cells in order to increase their productivity. This capability will dramatically reduce the timelines required to develop protein-based medicines, resulting in more available and cost-effective medicines for patients.
Improving cancer immunotherapy using G-CSF-blocking antibodies to overcome myeloid cell-mediated immunosuppression
Half of all Canadians will develop cancer and 1 in 4 will die of the disease. Cancer immunotherapy is a promising solution applicable to multiple types of cancer. The immune system plays a critical role in removing tumour cells. However, tumours escape the immune system to continue growing. Immunotherapy can enhance the immune system's ability to fight cancer and, in some cases, achieve long-lasting remission. However, many cancers do not respond to currently available immunotherapies.
In partnership with ME Therapeutics, we have developed antibodies targeting G-CSF, a protein overproduced by several major cancer types that induces immune suppression and may cause resistance to immunotherapy. Blocking G-CSF reduced the number of colon tumours and normalized immune system function in a mouse model of colon cancer.
We have selected a lead antibody that can successfully bind and inhibit G-CSF both in cell culture and mouse model systems. Our plan is to develop new animal models to test if blocking G-CSF can make resistant tumours sensitive to immunotherapy as well as to evaluate G-CSF in patient tumour tissue. Overcoming treatment resistance will substantially impact primary health care for cancer patients.
A GlycoCaged drug delivery system to improve the treatment of inflammatory bowel disease
Inflammatory bowel disease (IBD) is lifelong, debilitating condition that afflicts one in every 150 Canadians. Worryingly, the number of people diagnosed with IBD is rising worldwide, including among new Canadians and children. There is currently no cure for IBD, so treatment options are limited to managing symptoms with anti-inflammatory drugs.
Unfortunately, the oral administration of classical steroid IBD drugs is complicated by undesired side effects that result from premature uptake in the stomach and small intestine. Dr. Brumer and colleagues have recently developed a novel approach to link anti-inflammatory steroids to a complex carbohydrate from vegetables. This carbohydrate protects the steroids, allowing them to pass to the lower bowel, where they are released by beneficial bacteria of the microbiota.
Dr. Brumer and colleagues have validated this 'GlycoCage Technology' in the laboratory, including preliminary testing with human gut bacteria and in a preclinical animal model of IBD. The next steps in this research include further testing in additional animal models to determine dosage, safety, and efficacy. This will provide essential data before progressing to human trials and clinical application.
Dementia-Friendly Communities: Development of a Research Agenda
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People living with dementia and their family/friend caregivers face challenges including; stigma, poor physical health, social isolation, poor mental health, difficulty accessing formal and informal support and financial pressures. In B.C. in 2018, about 70,000 people live with dementia. By 2033, that number is estimated to increase to almost 120,000. In the face of an aging population there is increasing commitment across Canada to make our communities more 'age-friendly', but people with dementia may not be included in this. Social stigma and a lack of meaningful engagement strategies hinder people with dementia from participation in service development to create inclusive dementia-friendly communities.
The project aims to bring together researchers and research users to identify research priorities. We will collectively explore the meanings of dementia-friendly communities and develop a research agenda that includes shared vision and actionable research questions.
The team, including people with dementia and caregivers, will jointly plan a one-day research day workshop. The workshop participants include representatives of 6 stakeholder groups: researchers, people with dementia, family/friend caregivers, healthcare professionals, decision-makers of the local health authority, and dementia advocacy groups. Outcomes of this project will include a research agenda rooted in local community needs and a research advisory group to support subsequent research.