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.
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.
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.
“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.
Cancer is caused by mutations in the DNA that cause a patient’s cells to grow out of control. Some of these cancer-causing mutations change how genes are regulated; that is, which genes are turned on or off in the cell. Essentially all cancers have activated the TERT gene because TERT is essential for cancer growth. We understand TERT regulation better than most genes, but even here we cannot predict how mutations alter TERT expression. Overall, we do not understand which genes or mutations can promote cancer via altered gene regulation. Our work aims to learn the code that cancer cells use to interpret regulatory mutations. We will make many artificial mutations in large scale, and measure how much each mutation affects the amount of gene made. We will model how the cells interpret these mutations using a computer, and apply the model to find new cancer mutations. We will these computer models to discover how often mutations alter gene regulation in cancer, and highlight genes whose regulation is important in particular cancers. In the long-term, our work will allow us to better diagnose and treat cancer by showing how a particular patient’s tumor’s mutations alter gene regulation and cancer growth.
Spinal cord injury (SCI) is a debilitating condition with no available cure directly affecting ~80,000 Canadians. The major challenges to overcome include: i) the limited spontaneous regeneration of nerve fibers (axons) after the injury; ii) scar tissue formation at the injury site (lesion), which inhibits the growth of axons; and iii) the difficulty in guiding axons to grow across the lesion. The present work proposes a novel solution that combines optical stimulation technology and biomaterials to promote axonal growth, inhibit the formation of scar tissue using targeted drug delivery, and guide growing axons across the lesion. My team has developed fully implantable multifunctional neural probes for the delivery of both light and drugs to the spinal cord injury site as well as biomaterials to guide the growth to axons across the lesion. The MSFHR Scholar Program would support our work to integrate these strategies and create a therapy that helps us understand the combined effects of light stimulation, drug delivery, and axon guidance on motor function recovery after SCI in animal models. The outcomes will support treatment development for SCI based on a better mechanistic understanding of regeneration.
New technologies like single-cell RNA sequencing can observe biological processes at unprecedented resolution. One of the most exciting prospects associated with this new trove of data is the possibility of studying temporal processes, such as differentiation and development. How are cell types stabilized? How do they destabilize in diseases like cancer and with age? However, it is not currently possible to record dynamic changes in gene expression, because current measurement technologies are destructive. A number of recent efforts have tackled this by collecting snap-shots of single cell expression profiles along a time-course and then computationally inferring trajectories from the static snap-shots. We argue that this inference problem is easier with more data, and the right way to measure the “size” of a data set is really the number of time-points, not the number of cells. We propose to collect the first single cell RNA-seq time-course with more than one thousand distinct temporal snapshots, and we develop a novel mathematical and conceptual framework to analyze the data. This tremendous temporal resolution will give us unprecedented statistical power to discover the genetic forces controlling development.
The last decade has seen an explosion of genomic and health-related data. These data can advance precision medicine, but only if we apply the right analyses. I use statistical methods that link together many different types of large genomic and health datasets. My research identifies genomic mechanisms that lead to disease, which is the first step towards improving patient care. A primary goal of my research is to learn about the genes that cause mental illnesses like attention-deficit / hyperactivity disorder (ADHD) in children. We know that genes are important to ADHD risk. We also know that babies born small are at increased risk of ADHD, and that the placenta influences a baby’s growth in the womb. What we do not know, however, is how genes that are important to placenta function also affect a baby’s future risk of ADHD. Answers to this question will help us understand ADHD biology so that we can develop better prevention and treatment strategies and give all children the best start in life.
The response to COVID-19 has exacerbated gender inequity and gender inequities have limited the effectiveness of the COVID-19 response. This vicious cycle has been entrenched in past pandemics and will recur with future outbreaks, unless it is interrupted by intentionally transformative pandemic preparedness, response and recovery. This requires interdisciplinary research to better understand and respond to COVID-19’s secondary effects — defined as those caused by non-medical interventions to prevent primary effects (infection, morbidity and mortality). Secondary effects have long term health equity implications, with women and healthcare providers disproportionately affected. This research program aims to: 1) advance evidence of secondary effects among women and healthcare providers and 2) determine whether, how and to what effect public health policy has responded to these secondary effects. Three core projects and two collaborating projects will document the lived experiences of women and healthcare providers, while linking municipal, regional, provincial, and national level analysis to inform and promote equity-based pandemic response, recovery, and preparedness in BC and beyond.
The number of adults over age 65 in Canada is growing as baby boomers age. Older adults are the most likely to be diagnosed with cancer and likely to have other chronic health conditions. These health conditions may mean increased medications, medical appointments, and/or difficulties getting around, which combine to make the cancer experience more challenging. Older adults may also require help from family or friends to attend their many cancer and other health appointments (family doctor, geriatrics, and other specialists). COVID-19 has created additional challenges for older adults with reports of reduced or limited treatment offerings, and a sudden shift to virtual appointments.
My research responds to ongoing calls to rethink how we provide care for older adults with cancer. Specifically, we will partner with patients, community groups, health system leaders, and clinicians to co-create and implement tools to make cancer management easier for older adults. This work focuses on improving the processes rather than merely supporting individuals to navigate complex systems. This research will have important implications for health systems, clinicians, and researchers, but most significantly for older adults with cancer.