While Canada is currently one out of four countries globally to have no national restriction in law, the 2016 UN Human Rights Commissioner’s report indicated a lack of access to abortion due to cost, knowledge, and geography. For Indigenous Women, Two-Spirit, and LGBTQIA+ people in Canada, additional barriers exist including colonialism and racism. Yet there is an alarming gap in the literature surrounding Indigenous peoples and abortion services — despite knowing that one in three people in Canada will experience an abortion in their reproductive lifetime. The goal of this program of research is to build on existing community knowledge and strengths, advance knowledge around, and remove barriers to abortion services for Indigenous Women, Two-Spirit, and LGBTQIA+ people in Canada. Guided by an Indigenous feminist framework that acknowledges the intersectional experiences of Indigenous women, Two-Sprit, and LGBTQIA+ peoples and abortion access, this program of research will apply an Indigenous methodology to investigate experiences, gather knowledge, and co-develop resources to improve the abortion access gap among Indigenous peoples.
Program: Scholar
Examining motor imagery-related brain function in health and after stroke to leverage its prescription
Many stroke survivors (~85 percent) in Canada experience long-term impairments in arm and hand function. To aid recovery, motor imagery (the mental rehearsal of movement) shows promise as an adjunct therapy. Yet, its effectiveness is varied. We think this is due to a lack of basic knowledge about how motor imagery works. Motor imagery is thought to work similarly to physical therapy, whereby repetitive physical practice drives changes in brain function necessary for learning and recovery. However, we do not know a lot about how motor imagery drives changes in brain function. Using a blended approach not yet taken, we will examine changes in both brain function and behaviour driven by motor imagery. Importantly, we will examine how changes in brain function are altered and can be optimized after stroke, to improve its effectiveness. Findings will provide new information about how motor imagery should be applied to maximize learning and recovery, directly informing its use and prescription in stroke rehabilitation. Overall, this research represents a critical step in improving interventions for stroke recovery, leading to improved daily function and better quality of life for Canadians living with stroke.
Valvular heart disease and bioprosthetic heart valves: Defining mechanisms of degeneration and therapeutic discovery from bedside to bench
Aortic stenosis (AS) is a narrowing of the valve that controls blood flow from the heart to the body. AS results in significant decline in quality of life and can be fatal if untreated. Unlike most types of heart disease, there is no medication to treat AS and the primary therapy option is replacing the diseased valve with an artificial one by open-heart surgery or transcatheter implantation (insertion of an artificial valve through the blood vessels leading to the heart). Unfortunately, artificial valves can be dysfunctional and have limited durability, which can lead to heart failure, the need for repeat valve replacement, or death. With a focus on clot that can form on artificial valves, this research aims to determine the causes of valve dysfunction and degeneration, define methods to detect and predict which patients will experience valve dysfunction, and identify methods to increase valve durability. Overall, this work will provide critical new information to guide clinical care and the future evolution of artificial heart valve use that will improve the outcomes and quality of life of patients with AS.
Risk and protective factors for cognitive health across the adult age span: Impacts of physical and mental health and illness on cognitive outcomes
The virus causing COVID-19 can invade the brain, raising concern over long-term impacts on thinking abilities. We aim to identify long-term impacts on these cognitive abilities in those who have had COVID-19, and pinpoint factors that predict long-term outcomes. Adults positive for COVID-19 and those with no evidence of infection, are completing a series of cognitive and psychological tests in a current study. The proposed project will follow these individuals over time, with one and three-year follow-ups to examine changes in cognition across time. We will examine group differences in cognition, mental health, and other factors at each time point, determine if one or more cognitive profiles (clusters) characterize COVID-19 positive individuals, examine changes in these profiles across time, and test a screening measure to detect these cognitive difficulties. Findings will inform clinicians (e.g. neurologists, rehabilitation specialists) on trajectory of recovery of function and inform healthcare service provision in BC. Results will help ensure long-term impacts of infection are appropriately addressed, so those affected can efficiently resume complex activities requiring cognitive effort (e.g. employment, academic pursuits).
Fine-scale mapping of high dimensional brain imaging genetics
Brain imaging genetics looks at how differences in genes (the part of our DNA that makes us who we are) affect our brains. The connections between different parts of the brain, and the way the brain develops are all influenced by genes. Usually, when scientists look for genetic effects in the brain, they look for really broad characteristics such as the the sizes, or thicknesses of the different parts of the brain. This is useful for giving us a big picture about what’s happening, but it hasn’t led to any deep understanding of genetic neurodegenerative diseases (instead, it provides more of a description rather than an understanding). The main tool for measuring the brain in humans is magnetic resonance imaging (MRI). The MRI produces a three dimensional picture of the brain. The “pixels” of the picture are known as voxels (as they are volumetric). There are many voxels in each MRI picture, and the complexity and size of the picture is the reason scientists have so far only looked at broad effects. By using modern machine learning and statistical techniques, the challenge of looking for genetic effects at the level of the voxel can be overcome.
Self reactivity as a driver of extranodal diffuse large B-cell lymphoma transformation and survival
Lymphoma is a form of cancer that affects immune cells called lymphocytes, a type of white blood cell. There are many subtypes of lymphocytes and lymphomas. Diffuse large B-cell lymphomas (DLBCL) develop from B lymphocytes (B-cells) and are the most common subtype of non-Hodgkin lymphoma. About one third of DLBCL extend beyond the lymph nodes (“extranodal DLBCL”), and invade vital organs such as the kidneys, lungs, and brain, with an often-fatal outcome. Our ability to predict which patients will develop extranodal DLBCL is limited, and we also lack disease-specific treatments, partly due to an incomplete understanding of how and when these tumors originate. Interestingly, recent evidence suggests extranodal DLBCL share features with autoimmune disorders — conditions in which lymphocytes abnormally react against organs in our bodies, instead of external foes. In this study, we will investigate the relationship between the origin and progression of these diseases, in an effort to better understand how B-cells transform into cancerous cells, disseminate, and expand. Our work could help identify patients at high risk of developing extranodal DLBCL, and unveil key tumor dependencies to be leveraged as specific therapeutic targets.
Post-transcriptional regulation of hematopoietic stem cell function during normal and malignant hematopoiesis
In 2016, there were approximately 22,510 Canadians living with leukemia and an estimated 2,900 Canadians died from leukemia. Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. About 30 percent of AML patients eventually relapse after treatment and suffer from very poor overall survival at this stage. It is postulated that leukemia stem cells (LSCs), a small population of leukemia cells characterized with regenerative ability, mediate resistance and relapse after therapy. My work sought to uncover the largely unknown role of the processes that control protein generation in maintaining blood stem cells and how it contributes to transformation of leukemia stem cells in cancer. This research program aims to identify new factors, which can serve as targetable molecules and pathways to specifically eliminate leukemia cells while sparing normal cells. The work will provide the scientific foundation for future developments of therapy targeting these pathways as a novel strategy in eradicating leukemia stem cells to improve outcomes in AML patients.
Immunomodulatory effects of endogenous retroviruses in infection and inflammation
Infectious diseases and chronic inflammatory diseases plague human health and account for roughly 60 percent of deaths worldwide. Basic and translational research that reveal new mechanisms of immune modulation during viral infection and chronic inflammatory diseases are therefore critical to lower health burden. Genetic and environmental factors influence immune responses, but we are far from achieving a comprehensive understanding of mechanisms that underlie protective responses and unwanted excessive inflammation. Endogenous retroviruses (ERVs) are viral sequences that are major components of all human genomes, yet ERVs have been largely overlooked in the context of infectious diseases and chronic inflammation. Dr. Maria Tokuyama will develop a highly innovative and rigorous research program to identify novel interactions between ERVs and the immune system and determine interactions that boost antiviral responses in the context of viral infection and those that promote excessive inflammation in the context of chronic inflammatory diseases. This research will expand our knowledge of the underlying mechanisms of disease and will lead to health and economic benefits for Canadians.
Optimal pregnancy and postpartum health for everyone
After childbirth, mothers are at risk of death and disease. Patient engagement can improve the relevance and impact of research in this area; however, patient partners often do not reflect the diversity of the community. This limits the research and its results. This is especially important in BC, which is the most ethnically diverse province in Canada. The proposed research project aims to answer the following three questions: 1) How can we improve the diversity of patient partners in pregnancy and postpartum-related research? 2) Is a mobile application appropriate and acceptable for self-screening of postpartum complications? 3) What is the frequency, timing, and factors associated with postpartum complications and hospital readmissions in BC? The proposed research will promote equitable representation of pregnant and postpartum individuals in research, improving our understanding of their health and health concerns. It will be a core component of my portfolio of patient-oriented maternal health research in BC and globally.
Foot-Ankle Stability (FASt) solutions for lifelong mobility
“You need to improve your stability” is one of the most common pieces of advice offered by clinicians after an individual experiences a fall resulting in an injury. Despite this common advice, researchers are still trying to determine how to best keep a person stable as they age. Recent work has shown that foot and ankle structures may play a critical role in maintaining stability, but how this is accomplished varies from person to person, and may change as people age. In the game “Jenga”, players are required to remove blocks from within the stack and place them on the top of the structure; the blocks at the bottom are more difficult to remove than those closer to the top, as smaller movements at the base can cause the structure to collapse. Feet and ankles are much the same: If there are foot and ankle issues, the lack of stability at a person’s base can create small movement that ultimately contribute to a fall. My research will help researchers and clinicians fundamentally understand the importance of the foot and ankle to movements that are important for mobility (e.g. walking) and use this knowledge to create digital health solutions and assistive technologies aimed at maintaining mobility throughout the lifecycle.