Indigenous Peoples who use illicit drugs (IPWUID) are disproportionately affected by the drug poisoning crisis. Community-wide drug checking is a potential response to address the problem. Previous research has explored how best to implement drug checking as a response to overdose, as well as how to better include people who use drugs (PWUD) within drug-checking. However, Indigenous Peoples are not well represented in this research and Indigenous research approaches have not yet been undertaken. This study uses Indigenous research methods to better understand the needs and perspectives of IPWUID in accessing new drug checking technologies and services. It also explores the gaps in drug checking services for IPWUID in British Columbia (BC) and examines how unmet drug checking needs may affect their health outcomes. The outcome will be an Indigenous Harm Reduction approach to drug checking to inform new models and knowledge production approaches that best meet the needs of IPWUID.
Program: Trainee
Consequences of preconception bariatric surgery for fetal size and pathological growth restriction: a linked population registry study.
In Canada, 20-30% of reproductive-aged women suffer from obesity, which increases the chances that they will experience pregnancy complications. Preconception treatment of obesity with bariatric surgery reduces the risks of most pregnancy complications, but it increases the risk of having a baby measured in the smallest 10% (small-for-gestational-age, SGA). However, SGA is a poor indicator of fetal growth restriction (FGR), a condition where growth is impeded by a disease process. This distinction is important as FGR is associated with increased risks of neonatal complications, while most SGA infants are healthy. Whether preconception treatment with bariatric surgery is associated with increased odds of FGR is still unclear.
In this study, we will use a population database to evaluate the association between preconception bariatric surgery and the risk of FGR. Results of this study will be important to examine the balance between risks and benefits of preconception bariatric surgery in clinical care. Results will be diffused through scientific publications and presentations. Educational material, including infographic summaries and courses, will be created to disseminate findings to clinicians and patients.
SuPA Mobility: Supporting Physical Activity for Mobility in Older Adults with Mobility Limitations
Problem
As individuals age, they have a greater risk of limited mobility, or difficulty in getting around safely in one’s environment. Limited mobility is linked to illness, disease, and decreased quality of life.
Recent research show increasing physical activity by 6-minutes per day can improve mobility and prevent future disability. Despite the positive impacts on health, many older Canadians do not perform sufficient physical activity. Health coaching, a person-centered process to change behaviors with goal-setting, action planning, and feedback, is effective at improving physical activity participation in older adults. However, none of the previous health coaching studies included older adults with limited mobility.
Research
This study aims to address this knowledge gap to evaluate if health coaching can improve mobility and increase physical activity in older adults with limited mobility. We will conduct a 6-month study comparing health coaching to health education on improving mobility in older adults aged with limited mobility.
Potential Impact
Increasing physical activity through the use of health coaching has the potential to improve mobility and decrease the negative health impacts of limited mobility in older adults.
Uncovering metabolic mechanisms for tumor-driven immunosuppression with mass spectrometry imaging
Scientists have uncovered ways to turn the body’s natural immune system against cancer – an approach termed immunotherapy. While highly effective for some patients and cancer types, many patients do not respond. This creates a fundamental knowledge gap: why do only certain patients respond to immunotherapies? The answer may lie in the adage – “you are what you eat”. Cancers, at the cellular level, consume lots of fats, sugars, and 1000’s of other molecules collectively termed ‘the metabolome’. This leads to immune cells needing to fight for key fuels, and tumor cell production of toxic by-products which can kill natural immune cells. Together, this can incapacitate the immune system and may be why immunotherapies fail. Resolving this metabolic hurdle will require emerging, state-of-the-art technologies that can distinguish cancer cell metabolism and immune cell metabolism as they exist in the tissue (i.e. with their spatial distribution preserved). This project aims to develop and apply cutting-edge technologies to profile tumors which are responsive & unresponsive to immunotherapy, providing a fundamental understanding of tumor metabolism and allowing us to identify new opportunities to improve targeted immunotherapy treatments.
A personalized approach to non-physical practice after stroke
Chronic motor impairments are experienced by 85% of stroke survivors. Recovery of these impairments can be facilitated by repetitive non-physical motor practice including kinaesthetic motor imagery (KMI; the mental rehearsal of movement), visual motor imagery (VMI; specific focus on a mental image) and action observation (AO; passive observation of movement). Yet, effectiveness of these different non-physical practice modes is varied due to highly individualized brain function after stroke. To improve effectiveness, we will assess brain and behaviour changes driven by KMI, VMI, and AO at the individual participant level. We will then design a personalized intervention to show that improvements in motor function are maximized when practice mode is tailored to the individual based on the brain’s response to each mode. This research informs the development of evidence-based interventions after stroke, representing an important step in improving the quality of life of stroke survivors in Canada. Integrated knowledge translation (KT) activities (including engaging key knowledge users), and end-study KT activities (including public lectures of findings) will be conducted.
Addressing antimicrobial resistance through the design and preclinical evaluation of a Klebsiella pneumoniae vaccine
Antibacterial resistance occurs when bacterial infections become resistant to treatment. It is a serious and growing threat to global health. Klebsiella pneumoniae (Kp) is a bacteria that causes a wide range of infections, particularly in vulnerable populations such as children and immunocompromised adults. Kp can develop multi-drug resistance, which makes finding treatments difficult and increases the risk of severe complications or death. Finding novel treatments for Kp infections is a priority for both the World Health Organization and the Canadian government. Our goal is to develop a vaccine against Kp, which would reduce the incidence of Kp infection for both treatable and untreatable cases, and limit the opportunities for this bacteria to develop even stronger resistance to treatments.
In this project, I will focus on developing a vaccine that targets drug-resistant Kp. First, I need to identify vaccine targets that are present in most drug-resistant Kp infections. Then, I will develop vaccines using those targets. In the next step I will test whether our different vaccines protect mice from lung, bloodstream, and urinary tract infections. With these data, we will move the best candidate vaccine forward to clinical trials.
Developing novel strategies to enhance CAR Treg manufacture and testing in transplantation
After organ transplantation, patients must take immunosuppressive drugs to prevent rejection of the organ by their immune system. However, these drugs have severe side-effects. In contrast, regulatory T cell (Treg) therapy, which uses naturally suppressive immune cells to produce immunosuppression, can avoid these side-effects. Tregs for therapy can be isolated from patients, genetically modified in the lab, and infused back into patients to block unwanted immune responses without broader effects. However, improvements are still needed to this therapy. This project takes two strategies to enhance Treg therapy. Firstly, I will test the effect of supplementing lactic acid during cell growth in order to identify an optimal media composition that promotes function. Secondly, I will develop a human organ-in-a-dish system to model complicated transplantation immune responses in a lab without using mouse models, which often don’t replicate events in humans. Overall, this work will produce Tregs that function and survive better when administered to patients and develop a new way to test and model Treg function in a complex human system.
Engineering Transfusable Platelets for Improved Hemorrhage Control
Failure to control bleeding, such as during trauma and childbirth, accounts for more than half of all operating room deaths. Platelets are blood cells that stick to sites of active bleeding and release proteins to initiate blood clotting. The gold standard therapy for treating severe bleeds is transfusing the patient with more platelets. However, in some cases, transfused platelets can have impaired clotting, thus increasing mortality. A strategy to improve platelet function is to load platelets with more clot-initiating proteins. We have previously shown that platelets can be engineered to express new proteins using mRNA-lipid nanoparticles (mRNA-LNP). This project will expand on these findings and use mRNA-LNP to deliver the genetic blueprint for clot-initiating proteins into platelets to enable the production of clotting factors that will prime the platelets for improved clotting. The research will be in active collaboration with academic and industrial partners to facilitate the development of a clinical product from any generated intellectual property. Enhancing the natural properties of platelets will improve options for bleeding control, with the potential to reduce the incidence of hemorrhage-related deaths in Canada.
Investigating oncogenic mechanisms in DICER1 syndrome-associated ovarian Sertoli-Leydig cell tumors
DICER1 syndrome is a rare, inherited disorder; individuals with a mutation (change) in the DICER1 gene are at increased risk of a variety of cancerous and non-cancerous (benign) tumors. It affects mostly children and young adults. These cancers can be lethal at advanced stages of disease with no biologically-informed treatment strategies available. Despite the discovery of the gene, DICER1, being attributed to cancer development, the translation of this genomic discovery to the bedside to improve cancer care has been hindered by the lack of relevant models to study the disease. My post-doctoral research project will focus on one such aggressive rare cancer, called ovarian Sertoli-Leydig cell tumor. I will use the unique tools/resources such as a large cohort of patient samples and the first-ever mouse model of DICER1 syndrome-associated cancer to understand the biology of this rare ovarian cancer and identify potential druggable candidates for future therapeutic development.
Risk factors for cognitive impairment and substance-induced psychosis in people living in precarious housing or homelessness.
Social marginalization is a risk factor for poor health and is associated with psychotic and substance use disorders, traumatic brain injury (TBI), HIV and hepatitis C infection. Substance use and brain insults, such as TBIs, can lead to changes in brain function, yet we do not fully understand how they contribute to cognitive impairment (possibly due to accelerated aging) and other symptoms like psychosis. This study aims to assess the extent to which individuals with brain insults using substances are at risk of cognitive impairment or psychosis, and if using antipsychotics can affect these symptoms. This study will use data from the Hotel Study, an ongoing longitudinal community-based study aimed at characterizing factors affecting health of marginalized individuals based in Vancouver’s Downtown Eastside. Participants completed comprehensive assessments at study entry and monthly evaluations of prescription and non-prescription substance use, symptoms of psychosis, and annual cognitive assessments including brain imaging. Statistical modelling will be used to address objectives. We anticipate that our results will help better guide clinicians in engaging and treating this vulnerable population to prevent chronic disability.