We are studying if strength training exercises can reduce myelin loss and preserve cognitive abilities in adults with cognitive impairment due to vascular risk factors (e.g., high blood pressure), also known as vascular cognitive impairment (VCI).
Worldwide, VCI is the second most common cause of dementia and it is associated with myelin loss. Myelin is a component of neurons critical for transmission of brain signals. Thus, myelin is important for the maintenance of cognitive (i.e., thinking) abilities. Animal studies suggest myelin loss may be minimized with physical exercise. The objective is to determine whether strength training (e.g., lifting weights) is an effective strategy for slowing down myelin loss in persons with VCI.
We will conduct a 12-month study with 88 adults with VCI; half will receive strength training and half will receive balance and stretching exercises. At the end of study, the two groups will be compared on myelin content and cognitive function. Reducing myelin loss could preserve cognitive abilities in adults with VCI and reduce their risk of dementia. Our proposal is also timely as the prevalence and burden of VCI will only increase with the world’s aging population.
Mental health problems are estimated to be the most common disabling condition among adolescents worldwide, with children growing up in socially disadvantaged homes having up to three times the risk of mental health problems compared to children without such disadvantage. Studies show a high degree of intergenerational stability in these patterns, with social stressors putting particular subgroups of children at higher risk from the earliest stages of development. Immigrant and refugee children make up a significant proportion of the BC child population, and have a unique set of circumstances that may increase or decrease their risk of mental health problems as they reach adolescence. In BC, an established system of child development monitoring paired with new data linkages to provincial health, immigration, and Statistics Canada records create a globally unique opportunity to investigate continuities from maternal mental health problems to childhood emotional symptoms and adolescent mental health problems, for immigrant, refugee, and non-immigrant children. The purpose is to identify opportunities to break these continuities, informing the timing and design of preventative interventions to promote population mental health.
End of Award Update: December 2022
Most exciting outputs
This project opened a door for me to contribute to two integrated knowledge translation studies monitoring family, child, and youth
mental health during the COVID-19 pandemic. Working together with researchers and stakeholders from public mental health and
government, we brought urgent attention to pandemic-related population mental health trends among BC families and young people
through research reports, a policy brief, an op-ed, media interviews, and eight published articles. I was excited to at the same time
complete my original study on mental health among immigrant, refugee, and non-immigrant children and present these results at the
International Population Data Linkage Network Conference in 2022. Findings from this study suggested that BC children with
immigration backgrounds enter school with lower emotional health than children with non-immigration backgrounds and are likely to
benefit from increased social supports.
Impacts so far
Our research on child and youth mental health during the pandemic was referred to during a Debate of the BC Legislative Assembly
and referenced in a BC Ministry of Education report on Key Principles and Strategies for K-12 Mental Health Promotion in Schools. I
also had the opportunity to present this research to over 100 health professionals through the Centre for Health Evaluation and
Outcome Sciences Work in Progress seminar series, drawing attention and inviting conversation around the pandemic recovery
response for supporting the mental health of families and young people in BC.
Potential future influence
The connections I have made with researchers and stakeholders through this award have initiated a pathway for what I hope will be
many future opportunities to synergize between research, health services, and policy to make collective population health impacts at a
systems level.
Next steps
I will continue collaborating with colleagues and bridging connections between research and practice in my new role in a health
services research and evaluation position. Results from the immigration mental health study have been selected for submission to a
journal special issue and will hopefully become available in 2023!
Watch this presentation on the mental health impacts of the COVID-19 pandemic on students, parents, and teachers, produced for the Centre for Health Evaluation and Outcome Sciences (CHÉOS) Work in Progress Seminar Series, featuring Anne Gadermann, Kimberly Thomson, and Monique Gagné Petteni.
New toxins for incorporation into treatments known as antibody-drug conjugates are urgently needed to ensure therapeutic action. These antibody-drug conjugates consist of an antibody, designed to target a specific group of cells, attached to an active drug that elicits a desired cell response. While most emergent payloads for clinical application target tubulin, making them redundant, the death cap mushroom contains a toxic peptide called alpha-amanitin with unique biological activity. Amanitin presents its toxicity by preventing the conversion of DNA to RNA, a process required for protein synthesis. This inhibition ultimately leads to cell death. Amanitin’s high toxicity provides potential for a low dose cancer therapeutic if general toxicity to non-cancerous cells can be avoided. I seek to investigate the feasibility to harness amanitin’s bioactivity while delivering the toxin specifically to cancer cells by attaching a targeting agent. In order to facilitate these investigations, I will develop a scalable method to generate substantial amounts of the toxin. By utilizing this targeted approach, we anticipate a cancer cell-specific delivery of the toxin, which in turn would attenuate the off-target effects and general toxicity.
Acute myeloid leukemia (AML) has a dismal prognosis in Canada with only every 5th patient surviving 5 years. To find novel treatment options, we explore the therapeutic potential of the tumor suppressor microRNA (miR)-193a in AML patients together with InteRNA, a company that developed a novel drug based on the liposomal encapsulation of miR-193a (1B3), which showed very promising preclinical results in solid tumors and provided the rational for a phase I trial starting in spring 2020. We and others have previously shown that miRNAs are small RNAs that impact leukemia cells and are an emerging class of drugs. Recent data from our group showed a strong leukemia inhibition via miR-193a in animal AML models, highlighting the tumor suppressive effect of this miRNA. In addition, we are studying the regulation of miR-193a in AML cells to develop strategies to reinstate miR-193a expression and thus enhance its tumor suppressor function. This innovative study pioneers a novel class of RNA-based drugs in the treatment of AML and the groundwork for future clinical trials.
Transplantation is a cure for end stage organ failure, but a successful transplant requires a life-long use of immunosuppressive drugs to prevent organ rejection. The resulting lower immunity leaves patients in a complex medical condition because increases the risk for infections and cancer.
A specific type of immune cell, called regulatory T cells (Tregs), moderates the reactivity of the immune system and favours the transplanted organ acceptance. However, to maximize the use of Tregs as therapy, Tregs need to specifically recognize proteins on donor organs. A method to engineering Tregs to be specific to donor-organ is introducing a chimeric antigen receptor (CAR). However, currently available CARs may not work properly in Tregs and in a transplantation context.
This project aims to build this method by using different gene engineering strategies to maximize the success, safety and applicability of this technology in order to reduce the need of immunosuppressive drugs. The fine-tuning of Treg-based therapies for their use in transplantation could have important benefits to the health and life quality of persons with a transplanted organ, and could mean a huge advance in regenerative and personalized medicine.
Anxiety and depressive symptoms are the most common mental health problem in children born very preterm (24 – 32 weeks gestation). Our previous work found pain-related stress of frequent daily procedures during hospitalization across a period of rapid brain development and programming of stress hormone (cortisol) expression to be associated with later anxiety/depressive symptoms. Longitudinal studies examining how this vulnerability develops across early childhood in this population are scant. In an internationally unique longitudinal cohort of children born very preterm, I will examine whether early pain-related stress and neonatal brain development interact with levels of cortisol across childhood, altering trajectories of anxiety and depressive symptoms, at ages 1.5, 3 and 4.5 years, differentially for boys and girls. Moreover, I will identify specific parent interactions that may reduce anxiety/depressive symptoms across development. By identifying parent interactions that improve child outcomes at multiple levels (brain, stress and behavior), my research will lead to development of inexpensive, practical ways for parents to help their children, benefitting families in B.C. and beyond.
Cytomegalovirus (CMV) is a virus that is present in 50-90% of adults globally, depending on the region. When a woman either becomes infected for the first time or reinfected during pregnancy, she may pass the infection to her fetus, which often causes hearing loss and intellectual disability in the child. CMV is the most common congenital infection worldwide. Women usually become (re)infected with CMV from virus shed by young children but a better understanding of how children transmit CMV to mothers is critical for designing strategies to prevent congenital CMV.
We aim to determine how much shedding of the virus in saliva and urine of young children is required to transmit the infection to their mothers and what strains of virus successfully infect. To achieve this, we will collect samples from new mothers and their children for 1 year in Nairobi, Kenya, where rates of CMV infection are very high. Statistical testing will be used to evaluate risk factors for child and maternal (re)infection with CMV.
This research project will provide invaluable information on CMV transmission and will inform the development of a vaccine to prevent maternal (re)infection and the resulting harm to children from congenital CMV infection.
One in eight Canadians suffers from osteoarthritis (OA), a debilitating joint disease that frequently includes bone bruises, known as BMLs. The question we want to answer is, do BMLs result from changes in muscle strength and coordination, or poor condition of ligaments (connecting tissues) or cartilage (smooth joint lining) that cause the cartilage loading to increase? This study investigates whether BMLs might be a result of the loading environment of the knee. Though the exact cause of these bruises is not known, they have been linked to increased pain and worsening of OA. This study will measure the size and location of BMLs in people with OA and relate them to cartilage contact and stress (loading over an area). A unique standing Magnetic Resonance Imaging Scanner (MRI; i.e., looking inside the body with powerful magnets in an upright position) will be used to image OA patients during a knee bend. The BMLs will be mapped over the contact areas and stresses. Findings will provide insights into what positions (e.g. depth of a knee bend) yield contact and stress closest to the BMLs. If BMLs are linked to loading, clinical changes can be made to loading (e.g., bracing) or drugs may be taken to intervene.
Osteoarthritis is a painful joint disease and leading cause of disability that affects over 6 million Canadians. The knee is one of the most commonly affected joints. Knee osteoarthritis (KOA) starts with mild joint pain and stiffness that worsens to extreme pain, often requiring surgery if left untreated. Being able to identify people with KOA in primary care at an early stage of disease would help promote less invasive treatments. Yet, primary care clinicians report many barriers to identifying and treating KOA. The proposed study works with primary care clinicians and their electronic medical records to identify patients with KOA. I will examine the prevalence of KOA across Canada and learn about KOA risk factors like previous joint injury and obesity. As well, the management approach of primary care clinicians for KOA patients will be analyzed. Lastly, a secure online KOA dashboard will be pilot tested in a small group of primary care clinicians. This dashboard will combine the electronic medical record data with patient-selected patient reported outcome measures (PROM) on pain, symptoms, physical activity, and quality of life to inform primary care clinicians and guide their treatment for KOA patients.
Many neurodegenerative disorders are characterized by the accumulation of proteins forming toxic aggregates inside neurons. Certain proteins contain regions with repeated amino acids that can favor the aggregation process. In the cell, the molecular chaperone system maintains a fully operational protein environment by helping proteins reach and retain their final structure, prerequisite for their functionality. However, two chaperones (DNAJB6b and DNAJB8) were recently identified to also prevent protein aggregation and prolong the lifespan in Parkinson´s and Huntington’s disease mouse models, making them interesting potential therapeutic targets.
Our goal is to identify which proteins inside the cell require DNAJB6b and DNAJB8 for proper folding. We will identify the “client” proteins of the two chaperones by using protein mass spectrometry and biochemical methods. The validation of the newly found interactions, together with the determination of a pattern recognized by the chaperones, will allow the potential design of new therapies for the treatment of amyloid-based neurodegenerative diseases.
