Sepsis is a serious and life-threatening condition that arises from infections. Although medical advances have reduced the mortality rates of sepsis, many survivors have a weakened immune system and are at a higher risk for subsequent infections. Exercise represents a powerful tool to recover the immune system and reduce post-sepsis hospitalization. Through my research, I will explore how exercise impacts the immune system of sepsis survivors by specifically investigating immune cells called myeloid cells, which become dysfunctional following sepsis. Initial results in a mouse model of sepsis have found that four weeks of exercise improves survival to a subsequent lung infection due, in part, to restoration of immune system function and that female mice respond differently to sepsis than male mice. To understand this better, I will investigate how exercise changes immune cells and differences between sexes. In collaboration with an ongoing clinical trial in sepsis survivors, I will explore whether molecular changes in immune cells are present in human patients. Overall, my proposed research will lead to more effective exercise treatments for sepsis survivors to improve their quality of life and return back to health.
Program: Trainee
AID-PCD: Assessing Immunofluorescence for Diagnosis of Primary Ciliary Dyskinesia
Primary Ciliary Dyskinesia (PCD) causes microscopic hair-like projections called cilia to not function properly. Cilia sweep away germs that are breathed in but become trapped in mucous lining the airways. PCD causes frequent, severe sickness, which can require lung transplantation to prevent early death. Symptoms are seen at birth but diagnosis is frequently delayed due to problems with current tests. Electron Microscopy (EM) is one test for PCD, but only detects about 50-70% of cases. Genetic tests are more sensitive but we do not yet know all of the mutations that cause PCD, called Variants of Unknown Significance (VUSs). We recently created a new test for PCD using immunofluorescence (IF), which illuminates specific parts of cilia using a laser microscope. This test distinguished all PCD samples from healthy individuals. IF provides visual evidence that certain VUSs cause abnormal cilia. This test is also cheaper, faster and easier to interpret. Before IF can be used to diagnose PCD, we must show that it outperforms EM and genetic tests in a large group of patients from across Vancouver. This study will establish IF as a confirmatory PCD test, helping patients access personalized treatment and new gene-therapy clinical trials.
Heterogeneity of risk of substance-related harms in British Columbians – using machine learning and statistical models to predict individual overdose risk with administrative healthcare data
British Columbia is experiencing a public health emergency and toxic drug crisis. Statistical models help us understand this epidemic, and inform treatment and intervention strategies. An assumption of many existing models is that overdose risk is homogeneous throughout the population, ignoring individual risk factors such as past overdoses, treatment history, or other relevant features commonly available in administrative health data. However, key at-risk groups may be particularly affected by this assumption, as impacts may be underestimated. We propose a method of estimating individual overdose risk which leverages available health data. A number of machine learning models will be compared, with a focus on the mechanisms behind predictions, since a greater understanding of factors contributing to overdose risk can assist in targeting populations most in need of intervention and follow-on care. This work will be the first of its kind in BC. It will directly impact policy by providing a method of accounting for heterogeneity of overdose risk in existing models, improving estimation of intervention effects and forecasting, and practice, by the potential of direct application as a clinical tool in the distribution of care.
Validation and Implementation of a Wearable Cardiac Arrest Detection System in Clinical and Community Settings
Sudden cardiac arrest is a leading cause of death in Canada, often resulting in death within minutes if not treated. Quick recognition is crucial, but many incidents occur when no one is around to help. Our research aims to change this by using common consumer wearable devices, like smartwatches, to detect and predict cardiac arrest. Currently, smartwatches are unable to do this in a reliable way because these algorithms are not trained and tested on real cardiac arrest cases. We have collected this type of data from patients in hospices, undergoing medically assisted dying, and dying in the intensive care unit and trained highly accurate algorithms to detect cardiac arrest. In this project I will build an end to end cardiac arrest detection and alerting system which can use this algorithm to detect cardiac arrest, and complete the necessary steps to integrate it into the 9-1-1 system, building a foundation for real world community testing.
Our goal is to harness everyday wearable technology to improve the detection of cardiac arrest, enhancing survival rates and improving patient outcomes.
Educational pathways for holistic health and transformative social justice in prisons in British Columbia
Federal prisons deprive people of health education, which has adverse health impacts, including truncating opportunities for critical health literacy, agency, social inclusion and holistic health. The majority of people in prison have less than a grade ten education, and opportunities for learning are minimal. Despite evidence that education can support health literacy by increasing self-efficacy and socio-economic opportunities, there is a persistent gap between study findings and testing real-world benefits of formal education in prison. This Participatory Action Research will focus on developing and testing transformative social justice curriculum in two BC prisons, guided by the wisdom of currently and formerly incarcerated people. Anticipated outcomes are increased health literacy, positive identity formation, and improve holistic health. Knowledge mobilization focus on expanding and sustaining curriculum, working towards course accreditation, and work towards national policy change to improve health and education outcomes in prisons.
Unraveling the immunotherapy obesity paradox in triple-negative breast cancer
Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is particularly difficult to treat due to a lack of typical treatment targets. Obesity is linked to higher incidence of TNBC and worse cancer progression; as obesity rates rise, it is important to consider the effects of obesity on TNBC.
Cancer cells evade the immune system by deactivating immune cells. Anti-PD-1 drugs restore immune response against tumours, but most patients do not experience a benefit. Paradoxically, recent research suggests that obesity enhances anti-PD-1 therapy.
We will investigate the effects of obesity on lipid utilization in TNBC tumour and immune cells and anti-PD-1 effectiveness. We hypothesize that obesity will enhance anti-PD-1 and studying changes in lipid usage in tumour and immune cells will reveal mechanisms responsible for increased anti-PD-1 effectiveness. Mice will be fed a regular or high-fat diet and implanted with TNBC cells into mammary fat tissue. We will compare lipid profiles in the tumour and immune cells of lean versus obese mice and evaluate anti-PD-1 efficacy. By studying how obesity alters lipid metabolism in TNBC, we will uncover mechanisms responsible for modulating anti-PD-1 effectiveness.
Climate change and youth mental health and wellbeing: a population-based study and participatory knowledge-to-action project
78% of Canadian youth report that climate change impacts their mental health. This is important because mental ill-health during youth can have significant impacts over the lifetime. At the same time, youth feel powerless in addressing climate change, particularly due to government inaction.
This research seeks to uncover how negative emotions about climate change impact mental health in BC youth and what factors may protect against negative mental health outcomes. This research focuses specifically on factors of agency, for example activism and pro-environmental behaviours. I will use a large data set of more than 250,000 youth to learn about their mental health and climate change concerns. Additionally, I will work with 20 youth and two community-based organizations more closely to co-create a policy-level advocacy program and to understand the role of engaging in activism with regards to participants’ mental health. I believe this project will contribute to fostering the resilience and inter-generational support that youth will need as they take on the challenge of our generations.
Bridging the Gaps: Building Compassionate, Collaborative Responses to the Toxic Drug Poisoning Crisis in Small British Columbia Cities
Since 2016, over 15,000 lives have been lost to BC’s toxic drug poisoning crisis. Smaller urban and rural areas are disproportionately affected, often lacking resources and political support for vulnerable populations. Despite support for evidence-based harm reduction policies from the province and health authorities, municipal leaders have at times prioritized business and property interests over medical evidence and the voices of those impacted. My project will bridge healthcare responses, municipal actions, and the needs of those affected by the crisis. Working with Dr. Sharon Karsten within the research project Walk With Me and our existing partnership with Island Health, I will use document analysis, interviews, and community-engaged methodologies to explore health policy implementation in three Vancouver Island communities (Comox Valley, Nanaimo, Port Alberni), and identify communication and policy gaps between health authorities, municipal governments, and people with lived and living experience. Through direct collaboration, this project will foster connection among municipal staff, healthcare providers, and affected individuals, generating actionable insights to improve crisis responses and build lasting partnerships.
Exploring the Intersection of Race, Chronic Pain, Substance Use, and Overdose among People Living with HIV: A Mediation Analysis
As people living with HIV (PLWH) live longer due to effective antiretroviral therapy (ART), new health issues, such as chronic pain, have emerged. Research shows that PLWH with chronic pain may struggle with ART adherence and are at increased risk for substance use disorders and overdoses. However, there is limited knowledge on how chronic pain and overdose are connected in PLWH, especially if substance use disorders mediate this link. This project aims to close this gap. I hypothesize that PLWH who experience chronic pain are more likely to use illicit substances, which in turn increases their risk of substance use disorder and subsequent overdose.
Using data from the Comparative Outcomes and Service Utilization Trends (COAST) study, which includes comprehensive health data on all PLWH in British Columbia, this project will:
Analyze if PLWH with chronic pain are more likely to develop substance use disorders, potentially increasing overdose risk.
Assess whether racialized PLWH face greater overdose risk due to compounded challenges with chronic pain and substance use than White PLWH.
Develop knowledge translation guidelines to improve health outcomes for PLWH experiencing chronic pain and overdose.
Investigating gene-edited CAR T cells as an effective therapy in cancer
Large B cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma and causes a significant health burden. Cell-based therapies, including chimeric antigen receptor (CAR) T cells, have had great success treating B cell cancers, with about half of patients with lymphoma experience long-term clinical benefit. However, treatment of LBCL in individuals displaying significant extranodal disease (cancer presenting in peripheral tissues rather than/or in addition to lymph nodes) has been unfavourable and existing therapy must be improved. Thus, we have used a screening technique to identify genetic modifications that may promote CAR T cell functions in these difficult-to-treat sites. Candidate genes will be increased or blocked to produce more effective immunotherapy. CAR T cells harboring these beneficial gene modifications will be produced and their functional capacity assessed using culture-based assays. The modified CAR T cells will then be tested in mouse models of lymphoma to determine whether they have an enhanced ability to treat disease. The current study uses an innovative and unbiased method for discovery of targeted gene modifications that may be used in CAR T cell therapy to better treat extranodal B cell lymphoma.