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.
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.
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.
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.
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Research co-leads:
- Alison Phinney
University of British Columbia – Vancouver
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Research user co-lead:
- Dr. Lillian Hung
Simon Fraser University, University of British Columbia – Vancouver Campus, Vancouver Coastal Health
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Team members:
- Dr. Habib Chaudhury
Simon Fraser University
- Jim Mann
Alzheimer Society of Canada
- Mario Gregorio
Alzheimer Society of Canada
- Joyce Wong
Vancouver Coastal Health
- Shannon Hopkins
Vancouver Coastal Health
- Heather Cowie
Alzheimer Society of B.C
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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.
British Columbia (BC) and Canada have some of the world's highest rates of multiple sclerosis (MS). The goal of this research is to find out how safe and effective the drugs used to treat MS are when used in the everyday, real world in BC and Canada.
To achieve these study goals, I have two main study Themes. The first Theme focuses on how effective the MS drugs are. I will examine whether the MS drugs can extend life expectancy or prolong a person's ability to stay mobile and walk. I will also look at whether the MS drugs have a beneficial effect on reducing the number of times a person with MS is admitted to a hospital or visits a physician. The second Theme focuses on side effects, including whether the MS drugs are associated with harmful effects, such as cancer, stroke or depression. I will be able to compare the different MS drugs to each other. Also, I will see if men and women or people of different ages and with other illnesses (such as having both MS and diabetes) respond to the MS drugs differently.
My research findings will help people with MS and their physicians when trying to make decisions as to which MS drug might be best for them. Ultimately, this study will benefit the >90,000 people living with MS in Canada.
Mild traumatic brain injury (mTBI), commonly known as concussion, is a major public health concern. Around 42 million of the world's population sustain mTBIs annually. In Canada, ice hockey has the highest sports concussion rates in children and youth. In British Columbia, 2.4 million dollars were spent on hospitalization for mTBI in 2010. Furthermore, recent studies have linked multiple mTBIs from sports with heightened risk of long term brain changes. Despite the prevalence, the diagnosis and prevention of this condition is currently ineffective, due to the lack of knowledge of the injury mechanism.
In the proposed research program, I aim to gain a better understanding of the mechanism of mTBI. Specifically, I will study sports-related mTBI in ice hockey athletes, and investigate the effect of head accelerations on brain function. Players will be instrumented with mouthguard sensors to measure head motion and wearable electroencephalogram (EEG) sensors to measure brain response during practices and games. From the analysis of these data, we will gain a better understanding of the cause of injury. This understanding can help develop better diagnostic and prevention technologies to improve concussion management in and beyond BC.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths mostly due to the absence of symptoms as the cancer develops. This leads to diagnosis after the tumor has already become widely invasive and cannot be surgically removed. Unfortunately, surgical removal of early stage tumors is the most effective treatment option and other treatments, such as chemotherapy, are woefully ineffective.
Thus, there are two major fronts where research could improve the outcomes of pancreatic cancer patients:
- early detection and
- more effective treatments. Early detection requires knowledge of the events associated with tumor development, while improving treatments requires a thorough understanding of pancreatic cancer. It is clear that a 'one-size-fits-all' strategy has largely been ineffective for pancreatic cancer. We hypothesize that this is partly because PDAC is a 'catch-all' diagnosis for tumors that look the same, but may have different properties due to differences during their development. Our research program seeks to identify these differences and ultimately leverage the differences to improve patient outcomes through the development of personalized treatments.
Michael Smith Foundation for Health Research/The Pacific Alzheimer Research Foundation Post-Doctoral Fellowship Award
Millions people worldwide are currently afflicted with Alzheimer’s disease (AD). In the absence of a complete understanding of the disease, therapeutic trials have been unsuccessful and there still remains no cure. Biomarkers that can reliably detect AD at the earliest possible stage are essential for disease monitoring and drug therapy. The development of a biomarker for AD that can be translated to a rodent model of AD would also be useful in drug discovery. A validated biomarker could profoundly change the rate of the development and implementation of treatments for AD by enabling rapid high throughput screening of new drugs. Furthermore, the development of a robust method for biomarker detection which can be translated to a clinical laboratory setting would be an invaluable tool for AD diagnosis and monitoring. AD patients have deposits of proteinaceous plaques within their brains.
Our previous research has shown that a protein called melanotransferrin (MTf; also known as p97 or CD228) exists at high levels in humans with AD and is specifically expressed by immune cells associated with plaques in the brain. In contrast, healthy patients show a limited distribution of MTf. Of particular interest, the blood concentration of p97 is also elevated in AD patients compared to age-matched healthy human controls. These preliminary studies are promising but suffer from limited population size and the inherent uncertainty of current AD diagnostic methods (i.e. can only be truly diagnosed post mortem).
We plan to further validate MTf as an AD biomarker in mouse models of AD. This will be accomplished using a revolutionary diagnostic technology known as the SISCAPA assay. This platform offers reliable, robust absolute quantitation of proteins in complex biological fluids, and is already in use across the USA for the diagnosis of thyroid cancer. Using this clinically amenable method, we will monitor AD model mice, and wild type controls, throughout their life and correlate MTf concentration with the degree of neurodegeneration. It is expected that at a young age AD mice will be indistinguishable from healthy controls but as plaques appear in the brain, so too will MTf levels rise. These results will illuminate the timeline and intensity of MTf elevation as it relates to neuropathology. We will also establish the baseline for MTf in healthy or pre-AD subjects. These discoveries have the potential to change the course of detection and treatment of AD.
Michael Smith Foundation for Health Research/The Pacific Alzheimer Research Foundation Post-Doctoral Fellowship Award
Type 2 diabetes (T2D) patients have an increased risk of developing Alzheimer’s disease (AD). However, the underlying mechanism is poorly understood. Human islet amyloid polypeptide (hIAPP) aggregates, occurring in ~95% of T2D patients, induce a variety of pathological processes that are contributing factors to AD neuropathology. In current proposal, we attempt to investigate the effect of hIAPP aggregation on the Alzheimer’s development in T2D and the potential mechanism by conducting cell and animal experiments. Additionally, novel transgenic mouse models of diabetic AD will be generated to mimic the natural process of AD development in diabetics.
This study will help us to define the prevention and treatment of diabetic AD. Dissemination of the findings from this study will be done in different ways to make sure that the largest number of people will hear, understand and benefit from this novel research project. The experimental results will be published as research articles on academic journals and presented at scientific conferences, such as Society for Neuroscience annual meeting and Canadian Diabetes Association professional conference. Educational events and learning series will be held in the community, such as Cafe Science and public lecture series where we can engage the public with our research study, answer their questions directly and stimulate discussions.
End of Award Update
Source: CLEAR Foundation
Dr. Zhang’s research focused on creating a better understanding of why type 2 diabetes patients have an increased risk of developing Alzheimer disease. This research identified the important role of human islet amyloid polypeptide (hIAPP) in diabetes-induced dementia. Targeting hIAPP may be a valid approach for preventing and treating dementia in diabetes mellitus.
