Scholar – Page 16 – Health Research BC

Integrative genomics to identify novel therapeutics and biomarkers for COPD

Chronic obstructive pulmonary disease (COPD) affects 300 million people worldwide and is the third leading cause of death, responsible for over 3 million deaths per year. It is the number one reason why adults end up in hospitals. However, we do not have good drugs to treat patients with COPD. This is because we do not fully understand how and why COPD develops and progresses.

Smoking can cause COPD but not all smokers get the disease; our genes also play a role. Identifying which genes cause some people to get COPD or lead to disease worsening over time will allow us to understand these processes more and to develop new drugs to treat the disease.

This project will use sophisticated analysis tools called integrative genomics. First, we will identify regions of our DNA that are important for COPD risk and worsening over time. This will be done through studying DNA regions from thousands of subjects with and without the disease and on whom we have information on how well their lungs work. We will then identify the function of these DNA regions by uncovering their effect on gene products and proteins in tissues that are important and relevant for COPD such as lung and blood. These genes and their products will be tested in laboratories to confirm the findings. The goal is to use this information to monitor disease and will additionally allow us to interfere with these gene products to treat disease.

Studying the role of modifiable risk factors: Nutrition and body weight for the prevention of cancer

Nearly half of Canadians will be diagnosed with cancer during their life. Healthy eating, a healthy body weight, and regular physical activity can prevent one-third of cancers. Yet, many Canadians do not engage in these lifestyle behaviours. New approaches to improve diet-cancer research are needed to move the field forward and reduce the burden of cancer on Canadians.

Dr. Murphy's research focuses on modifiable risk factors for cancer; nutrition and body weight. The goal is to provide new insight on how and why these factors contribute to cancer development using data from large populations of Canadians and innovative approaches such as lifestyle biomarkers that may explain why factors lead to cancer development.

Advances in cancer prevention are needed to promote the health of people in BC and nationwide. This research will provide new insight into modifiable factors for cancer that may help encourage lifestyle changes and development of new strategies to prevent cancer.

Predicting depressive symptoms during the transition to high school

The transition to high school is a challenging developmental period, during which prevalence rates of depression more than double. In fact, by the end of the first year of high school, 11.5% of adolescents will have experienced a depressive episode in the last year, and many more adolescents will have experienced elevated depressive symptoms that interfere with school performance, social friendships, or physical health. Despite the importance of this transition, little is known about predictors of depression during it, and most students report feeling insufficiently supported to cope with it. Thus, the proposed research will work towards answering two questions critical to Canadian youth:

What causes adolescents to develop depression during the transition to high school?
What can we do to help students better cope with this transition and to mitigate risk for depression during it?

Findings will be critical to improving students' emotional health during the high-school transition. Knowledge translation activities will inform future research, practice, and policy.

A program of research on criminalization of sexuality, HIV and incarceration among marginalized women

Marginalized women (trans inclusive) living with and affected by HIV are disproportionately criminalized. This research will establish an empirical evidence base that documents the lived-experiences of criminalization and incarceration among sex workers and women living with HIV. The ultimate goal is to inform evidence-based law reform and interventions to redress over criminalization and negative effects of incarceration.

The objectives of this research program are to:

Document how evolving laws and policy frameworks governing sexuality (criminalization of sex work; criminalization of HIV non-disclosure) impact HIV care trajectories, sexual health and social inequities among sex workers and women living with HIV.
Describe and monitor the impacts of incarceration on HIV care trajectories and social outcomes among women living with HIV.
Identify and pilot novel structural and community-based interventions to mitigate the impact of incarceration on HIV care trajectories and social outcomes among women living with HIV.
Develop a research and training platform for innovative community-based participatory research approaches to inform program and policy interventions.

Imaging repair: Developing and applying unconventional neuroimaging methods for quantitative assessment of tissue health

Magnetic resonance imaging (MRI) is a powerful tool for measuring changes in the brain and spinal cord that occur over the course of neurological disease. Unfortunately, conventional MRI is qualitative, so the biological cause of the changes seen on MRI is difficult to determine.

Damage to myelin, the substance that surrounds the nerve fibres (axons) of the brain and spinal cord to speed up signal transmission and protect the axons themselves, is a common feature for many neurological diseases. While myelin can be repaired, axonal damage is irreversible.

Dr. Kolind is focused on developing and applying advanced MRI techniques that provide measures related to myelin loss or axonal damage. The greater sensitivity and specificity afforded by these advancements provides critical information regarding the underlying processes in neurological disease. This insight is needed to understand such diseases and target treatment development. Further, the quantitative nature of these techniques may dramatically reduce the number of patients and time period required for successful demonstration of new therapies. This approach has tremendous potential for clinical trials and research studies in countless neurological diseases and injuries.

Platelet signaling in chronic inflammation

Proper function of the immune system is essential for protection against infectious disease and maintaining human health. During the onset of infection, white blood cells and platelets release signaling molecules known as cytokines, which orchestrate a protective inflammatory response. When cytokine release is de-regulated, excessive inflammation causes cell and tissue death and loss of function. This is seen in gum disease (periodontitis), which is characterized by gum inflammation and destruction of tooth-supporting connective tissues and bone. This research will uncover the mechanisms responsible for maintaining the health of periodontal tissues.

Platelets, in addition to regulating blood clotting, are emerging as pivotal components of the inflammatory response. Dr. Kim and team will study how periodontal infection causes cytokine release from platelets, focusing on:

How human platelets respond to periodontal infection and determine how platelet function correlates with clinical gum disease status.
How the cell's structural framework mediates the release of cytokines from platelets.

An improved understanding of platelet function could have important implications for rational treatment of inflammatory diseases, including gum disease.

A causal inference framework for analyzing large administrative healthcare databases with a focus on multiple sclerosis

Provincial health authorities routinely collect patient information on a massive scale, but health researchers face the challenge of exploring cause-and-effect relationships using these non-randomized population-based data sources. Machine learning methods are increasingly used to analyze these large datasets, although they do not inherently take causal structures (i.e., how the variables affect each other) into consideration and may lead to less-than-optimal or even erroneous conclusions.

Health researchers urgently need new big-data analytic methods that are geared towards extracting causal explanations rather than merely increasing prediction accuracy. This project will develop innovative biostatistical methodologies that will better equip health researchers to infer causation from big-data sources.

As a motivating problem, with a bias reduction goal in mind, Dr. Karim will investigate potential benefits of disease-modifying drugs in multiple sclerosis patients 50 years of age or older. Ultimately, this methodological development will enable health researchers to convert information into actionable knowledge for other common, chronic conditions, leading to cost-effective medical decision making and improving the health of Canadians.

Population-based ‘big data’ research to improve women’s health

Dr. Hanley's research in women's reproductive health uses the large population-based datasets that already exist in British Columbia, and is driven by diverse training in population and public health, health services research, and economics.

Specifically, Hanley will study whether removing a woman's fallopian tubes at the time of other routine gynecologic surgeries is a safe, effective and cost-effective ovarian cancer prevention strategy. This will provide much needed and timely evidence on the effectiveness of removing the fallopian tubes as an ovarian cancer prevention strategy. Known as the British Columbia protocol, this practice has been adopted in many countries around the world.

Hanley will also examine the safety of using psychotropic medicines during pregnancy, specifically whether using antidepressants during pregnancy may increase a child's risk for autism spectrum disorder and social and emotional and motor development in early childhood. This will generate evidence that can be used to minimize or avoid adverse outcomes from maternal mental illness and use of prescription drugs to treat that illness in pregnancy.

This focus on women's reproductive health and the use of the large linkable population-based datasets in BC will generate evidence on improving population health, improving patient care, and reducing health system costs. This research has already, and will continue to, guide patient care in British Columbia.

Mental health trajectories of immigrant and refugee children: An ecological population-based approach

Canada’s immigrant and refugee population is growing rapidly, representing over 20% of the population. Despite the significance for Canadian society, little is known about mental health and risk factors among immigrant and refugee children and youth. Such knowledge is, however, critical to understand how we can support them in adapting to Canada, and enhance their well-being. This project aims to create actionable evidence that health professionals, educators, and decision-makers can use to implement initiatives that can support the mental health of immigrant and refugee children and youth.

This research will:

Use statistical analyses of multiple databases, linked at a population-level across 10 school districts of BC, to examine how child, family, school, and community factors relate to immigrant and refugee children’s mental health outcomes, and how these children and youth are using health services in BC.
Ask immigrant and refugee youth about their perspectives on factors related to their mental health and access/barriers to mental health services, via interview focus groups in school and mental health clinic settings.

This is the first study in BC to combine province-wide data with children’s own perspectives to identify which factors may need to be addressed and what future prevention and intervention efforts are needed to support long-term health outcomes for immigrant/refugee children and youth in Canada.

End of Award Update – June 2023

Most significant outputs

This project allowed us to study and identify population-level diagnostic prevalence of mental health disorders across immigrant, refugee, and non-immigrant children and youth in British Columbia (BC). In this research, we found notable differences in the diagnostic prevalence rates of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and mood/anxiety disorders across immigrant, refugee, and non-immigrant children and youth, as well as across factors such as sex, age, and immigrant/refugee generation status.

This project also allowed us to delve more deeply into the factors that might impact the emotional health of refugee children. This research identified that specific factors associated with refugee children’s perceptions of their social context (e.g. a supportive school climate, support from adults at school) were associated with better emotional health.

Impact

To our knowledge, our research is the first to provide population-level mental disorder prevalence estimates that compare immigrant, refugee, and non-immigrant groups in BC. This provides important information to our understanding of the mental health status of immigrant and refugee children and youth in BC.

Potential Influence

We hope that this work will be the impetus for additional research examining the unique mental health patterns and needs of diverse child and youth sub-populations that tend to be underrepresented in mental health research. Understanding the unique needs of Canada’s diverse sub-populations is particularly important for health service planning and informing health policies.

Next Steps

With the support of a Tier 2 Canada Research Chair and funding from the Canadian Institutes of Health Research and Social Sciences and Humanities Research Council of Canada, we are continuing our work to deepen our understanding of the developmental trajectories and unique mental health needs of diverse children and youth in BC.

Neuromodulation research program for youth addiction and mental health

Each year, approximately 1 in 5 Canadians experiences a mental health or addiction problem. Young people aged 15 to 24 are more likely to experience mental illness and substance use than other age groups.

Depression is one of the most common mental illness, but current treatments are either ineffective or lead to side effects in up to 50% of youth. In youth, medications are often borrowed from adult population not accounting for age-related brain differences. New solutions are needed to address major gaps in treatment of youth mental health.

Dr. Farzan is collaborating with physicians, neuroscientists, engineers, and health authorities to develop and apply more precise and innovative methodologies to study the brain and address this gap. She is combining non-invasive brain stimulation and brain monitoring technologies to study what may underlie depression in young age, and how each treatment affects the brain. She is also developing non-invasive brain stimulation technologies for youth that do not respond to medications or behavioral therapy. This research has tremendous potentials for leading to introduction of a new therapy for youth who are failing currently available treatments.