Over half of Canadians have experienced at least one childhood adversity (CA), which is linked to an increased risk of poor health and wellbeing across the lifespan. Current approaches have focused on linking CA to poor outcomes, yet this approach overstates the impact of risk and devalues the importance of protective factors enabling individuals to withstand, adapt, and recover. The focus on outcomes may also fail to capture the trajectories of wellbeing and cyclical nature of resilience and vulnerability.
This program of research utilizes a mixed-methods approach to explore pathways to wellbeing in the context of CA, focusing on the timing and type of protective factors. To fully understand how socio-environmental and biological factors contribute to health and wellbeing inequity due to CA, we must examine the pathways to impairment and wellbeing using a developmentally informed framework. Changing the question from ‘how are youth at risk’ to ‘how do youth adapt,’ and shifting to a model where those with trauma histories are not defined by their risk. Findings will produce actionable evidence for practitioners and policymakers to develop early intervention and prevention programs fostering health equity for those with CA.
One in every 58 children in British Columbia meet criteria for autism spectrum disorder (ASD) — an increasingly common developmental disorder characterized by notable social and communication difficulties. Co-occurring mental and physical health conditions are the rule, rather than the exception for those on the spectrum and associated with poorer outcomes as well as more complex and costly healthcare needs for affected families. Childhood trauma is a major risk factor for physical and mental illness that has been understudied in ASD and for which there are few evidence-based guidelines. Clinical research and practice have been limited by a lack of assessment tools designed to account for the different ways in which youth with ASD may experience and express psychological trauma.
The goal of this proposal is to address this measurement gap and therein enable the applicant to develop a unique research program focused on improving the recognition, characterization, prevention and treatment of traumatic events and symptoms in autistic youth and young adults. Stakeholder engagement and knowledge translation activities will be used throughout to guide the development of measures and to inform future research, practice, and policy.
Pluripotent stem cells (PSCs) have the ability to expand endlessly, making copies of themselves, as well as to differentiate into all specialized cell types of the body. As a result, PSCs have opened the door to deriving cellular therapies that have unprecedented promise for treating degenerative diseases. Despite this promise, we lack an understanding of how to control their behaviour — whether they divide, die, or differentiate.
My laboratory will use a combination of cutting-edge experimental and computational technologies to study PSC fitness — the ability of these cells to eliminate each other via cell-cell killing. Our research will uncover the genetic basis of their fitness to predict the emergence of abnormally competitive PSCs, those with aberrant genetic mutations, and to use synthetic biology tools to remove these from cell manufacturing batches. We will also engineer PSCs to enhance their fitness, allowing us to grow these cells in the lab with better efficiency and safety. This research will lead to health and economic benefits for Canadians, improving the efficacy of cell therapies and building on our legacy of stem cell research that began with the initial discovery of stem cells in 1961 by Drs. Till and McCulloch.
The inability of patients to perform daily tasks after joint replacement remains a significant challenge as well as a burden on health systems because these poor results often require additional treatment (e.g. rehabilitation) and re-replacement. This challenge can be addressed by surgeons using individual patient characteristics to personalize how they perform joint replacement surgery. However, many surgeons perform too few procedures to effectively personalize their plans and thus technologies are needed to provide assistance.
The goal of this research is to develop an improved understanding of how patient specific factors affect the results of joint replacement as well as to develop technologies that can collect data about each patient’s individual characteristics and use these data to assist surgeons in optimally planning each surgery. This will be achieved by a combination of computer-based biomechanical research, statistical modelling, and novel sensor development. This work will improve our understanding of personalized joint replacement, yield new clinical technologies, enable surgeons to more effectively personalize surgery, result in improved patient function, and improve the health systems in BC and beyond.
Female reproductive decline (indicated by rising rates of infertility, birth defects, and miscarriage) is an early sign of aging, and is largely due to deteriorating quality of oocytes, or egg cells. Identifying the signaling pathways and mechanisms that control oocyte quality and reproductive decline is essential for better addressing female reproductive health issues, and can also provide key insights into other aspects of aging.
Our research focuses on the ties between nutrients, reproduction, and aging. In organisms ranging from worms to humans, signaling pathways that detect nutrients — such as the insulin signaling pathway — seem to play crucial roles in coordinating metabolism, reproduction, and lifespan. We will use a mouse model of genetically reduced insulin to determine how lowering insulin affects oocyte quality and reproductive success during aging. We will also study how insulin levels determine features of polycystic ovary syndrome, a common hormonal disorder, and evaluate long-term consequences of temporary nutrient excess or depletion.
We anticipate that this research will inform effective strategies to better manage female reproductive health, as well as to improve health during aging.
Proper myelination allows for the fast, efficient transmission of nerve impulses which is important for the coordination of movement, integration sensory information and cognition functions. In the brain, oligodendrocytes are the cells that extend numerous processes that wrap nerve cell (neuron) processes in a compact myelin sheath.
The overarching goal of my research program is to delineate the cellular mechanisms that underlie myelination across an organism’s lifespan. Several interconnected research projects investigate different aspects of how myelination occurs in the brain, such as the regulation of gene expression in oligodendrocytes, the cellular communication between oligodendrocytes and neurons, and the impact of environmental factors. These projects use animal models to investigate these biological questions at the molecular level (e.g. DNA, RNA, proteins and lipids). New insights into how these molecules interact to regulate myelination has broader implications for brain development, aging and pathology. This will ultimately lead to better health outcomes for persons living with neurological disorders.
More than 20 percent of candidates on the kidney transplant waitlist are considered difficult-to-match for the already scarce resource of kidne y organs. This is because their immune system has previously been activated through pregnancy, blood transfusion, or prior organ transplants to produce a broad range of antibodies that limit their chances of finding compatible donors. These “highly sensitized” patients (HSP) face prolonged wait-times, reduced access to transplant, and an increased risk of death on the waitlist.
The main objective of this research is to implement a first-of-its-kind Willing to Cross (WTC) program. Under this national initiative, patients will be able to be transplanted across known antibodies against donors that are deemed to be at low risk of causing rejection. This strategy is anticipated to improve the chances of receiving a transplant while maintaining good patient outcomes. In addition, the study will follow patients with two cutting-edge immune assays that have been shown to detect rejection before kidney injury occurs. Recognizing that we serve a diverse patient community with different values and beliefs, we will also evaluate patient perception and readiness to adopt this new kidney allocation system.
Neurodevelopmental and fertility disorders represent significant health burdens in Canada, as approximately 1 in 66 Canadian youth are diagnosed with an autism spectrum disorder, and 1 in 6 Canadian couples experience infertility. Neurons and reproductive cells (oocytes and sperm) rely extensively on a form of control of gene expression called translational control. Mutations in the translational regulatory gene Fmr1 underlie the fragile X disorders known as fragile X syndrome (FXS) and fragile X primary ovarian insufficiency (FXPOI), which are leading causes of autism and premature ovarian failure respectively.
The proposed research will build upon my recent discoveries of Fmr1’s role in promoting the translation of genes encoding large proteins — many of which are associated with autism — in order to understand the mechanism by which Fmr1 activates translation. Knowledge of this mechanism will be of immense clinical value, enabling the development of novel therapies for citizens of British Columbia experiencing a fragile X disorder or related autism spectrum or infertility disorder.
In Canada, approximately 7,600 adolescents and young adults (AYAs) aged 15 to 39 are diagnosed with cancer each year, representing 4 percent of annual cancer diagnoses. Currently, cancer care systems have limited capacity to meet the complex needs of AYAs and survival outcomes for AYAs are often worse when compared to children and adults over 40.
This research program will use the principles of participatory action research (PAR) and patient-oriented research (POR) to meaningfully engage AYAs and cancer care allies (healthcare professionals, decision makers, researchers, and community organizations) to better understand AYA cancer care and explore how cancer care systems can respond to the unique, complex needs of AYAs with cancer. Led by a researcher with lived experience of cancer as an AYA and 15 years of experience conducting PAR, the work seeks to inform AYA cancer care research, policy, and practice in BC and beyond. Initial research funding from the Vancouver Foundation, MSFHR, and British Academy is in place, as are collaborators from Royal Roads University, BC Cancer, BC Ministry of Health, Young Adult Cancer Canada, the BC SUPPORT Unit, Callanish Society, InspireHealth, Innovation Support Unit, and AYAs with cancer.
Obesity is one of many chronic conditions that are rising in Canada, with heart disease as the top killer for women. Social inequalities exist in these conditions, but few studies focus on the social causes of obesity in women versus men, or on how social causes reinforce each other.
My research program aims to fill these knowledge gaps so that interventions to prevent and manage chronic conditions can be better designed and more effective. One of my projects is focused on co-developing novel ways to promote heart health among Indigenous women because of the profound burden of CVD in one of Canada’s most marginalised group. A key program goal is to produce strong research evidence to inform public health strategies and interventions for preventive action on obesity, and to build capacity of the next generation of researchers and healthcare providers to further improve health and health equity in Canada, especially BC.