The Problem: Avascular necrosis (AVN) is a serious complication of corticosteroid treatment in some children with cancer, causing bone damage and, in severe cases, requiring surgery. It affects quality of life and places additional burdens on families and healthcare systems. Currently, there are no reliable ways to predict or prevent severe AVN.
Overview of the Research: In a study of 972 children with cancer, I identified four genetic variants strongly linked to corticosteroid-induced AVN. This project will explore how these genetic factors influence AVN risk by validating key predictors in 718 additional patients, pinpointing causal variants, and investigating how these genes affect bone cell responses to corticosteroids.
Anticipated Outcome: Development of a genetic test to identify children at high risk for severe AVN.
Potential Impact: A genetic test for AVN risk would allow doctors to personalize treatment plans for children with cancer. Children identified as high-risk could be monitored more closely or given alternative treatments to prevent AVN from developing in the first place. This would significantly reduce the number of children experiencing this painful and debilitating side effect.
Solid organ transplantation is often the last treatment option for people whose kidneys, liver, lungs, or heart are failing. Unfortunately, the long-term success of organ transplantation is limited by the delicate balance between the risk of organ rejection and the serious side effects caused by anti-rejection drugs. To improve transplant outcomes, we have developed a new treatment approach using engineered immune cells called “CAR Tregs.” In early tests using mice, CAR Tregs have been shown to help extend the life of transplanted skin, and heart. In human transplant patients, CAR Tregs will need to be tested alongside traditional anti-rejection drugs, which work by blocking the normal function of all immune cells, including CAR Tregs. My research aims to engineer CAR Tregs to be resistant to the negative effects of anti-rejection drugs, so they can work together with anti-rejection drugs to better prevent organ rejection while using lower doses of drugs. The findings from my research will inform the design of future CAR Treg clinical trials with the ultimate goal of improving the quality of life for transplant recipients through the reduced need for harmful medications.
Our bodies contain unique molecular markers that can reveal important information about our health, but analyzing these markers is challenging due to the vast amounts of noisy and complex data. Our research aims to develop new computational tools that make it easier and more cost-effective to interpret these molecular signals, with two main goals: First, we’re creating methods that could be applied to detect cancer earlier through blood tests by detecting fragments of DNA from various organs in the body. Second, we’re studying how environmental factors in early life influence prenatal and long-term health by examining what causes these molecular changes. We will create user-friendly software tools that enable scientists and doctors to analyze molecular data more effectively and affordably. This could lead to better cancer screening tests and help us understand how early-life experiences affect health. We’ll also evaluate how well these tests work in different healthcare settings to ensure they benefit diverse patient populations. Ultimately, our work will advance both cancer detection and our understanding of child development while making cutting-edge molecular analysis more accessible to the research community.
A surge in eating disorders during the COVID-19 pandemic has contributed to a workforce crisis. Our team’s research shows that one-third of Canadian eating disorder clinicians are considering leaving their job. Currently, eating disorder services are primarily based in limited specialized programs. However, an innovative early intervention model in general mental health settings is being developed for the Canadian context. In this model, integrated youth services play a core role in rapid response. This capacity building model has significant promise, yet it is unknown how to best support clinicians working with this model.
The project will bring together researchers and research users for a full-day interactive event, to co-develop a research strategy for eating disorder early intervention in BC. The research agenda will focus on two key questions: (i) what are the barriers and facilitators to implementation of early intervention across BC service settings; and (ii) how can we best evaluate early intervention outcomes, and the impact of this service model on clinicians who provide care for eating disorders.
The project outcomes will be integrated into a pan-Canadian strategy for eating disorders early intervention research.
The Neonatal Intensive Care Units (NICUs) at BC Women’s Hospital and Victoria General Hospital care for >2000 critically ill babies each year. Many of these babies are sick because they have genetic conditions which can be very difficult to diagnose (the disorders are rare and many of these babies are premature). There is a new test called genomic sequencing (GS) that looks at a baby’s entire genetic code and can detect a change that may be responsible for the baby’s medical problems. This test has revolutionized the ability to diagnose babies with genetic disorders and is ordered for many babies in the NICU. The results can be difficult to interpret for the doctors who order the test (often it is not clearcut as to whether the change is causing the disorder and sometimes medical problems can be discovered that are not part of the baby’s condition (e.g., risk for cancer). The NICU team is composed of doctors, nurses and other healthcare workers (but not genetic counsellors). We conducted a study of the NICU staff that showed they are not comfortable ordering GS, interpreting the results and want more education about GS. In this project, we will develop educational tools to help the NICU staff look after babies who have had GS.
After organ transplantation, patients must take immunosuppressive drugs to prevent rejection of the organ by their immune system. However, these drugs have severe side-effects. In contrast, regulatory T cell (Treg) therapy, which uses naturally suppressive immune cells to produce immunosuppression, can avoid these side-effects. Tregs for therapy can be isolated from patients, genetically modified in the lab, and infused back into patients to block unwanted immune responses without broader effects. However, improvements are still needed to this therapy. This project takes two strategies to enhance Treg therapy. Firstly, I will test the effect of supplementing lactic acid during cell growth in order to identify an optimal media composition that promotes function. Secondly, I will develop a human organ-in-a-dish system to model complicated transplantation immune responses in a lab without using mouse models, which often don’t replicate events in humans. Overall, this work will produce Tregs that function and survive better when administered to patients and develop a new way to test and model Treg function in a complex human system.
In Canada, 20-30% of reproductive-aged women suffer from obesity, which increases the chances that they will experience pregnancy complications. Preconception treatment of obesity with bariatric surgery reduces the risks of most pregnancy complications, but it increases the risk of having a baby measured in the smallest 10% (small-for-gestational-age, SGA). However, SGA is a poor indicator of fetal growth restriction (FGR), a condition where growth is impeded by a disease process. This distinction is important as FGR is associated with increased risks of neonatal complications, while most SGA infants are healthy. Whether preconception treatment with bariatric surgery is associated with increased odds of FGR is still unclear.
In this study, we will use a population database to evaluate the association between preconception bariatric surgery and the risk of FGR. Results of this study will be important to examine the balance between risks and benefits of preconception bariatric surgery in clinical care. Results will be diffused through scientific publications and presentations. Educational material, including infographic summaries and courses, will be created to disseminate findings to clinicians and patients.
Organ transplantation, the primary treatment for organ failure, necessitates lifelong immunosuppressive therapy. Traditional immunosuppressants like steroids pose risks of severe infections and cancer due to their non-specific action. To address this, we’ve developed engineered Tregs, which migrate specifically to transplanted organs and prevent rejection. Initial studies in mice demonstrate promising delay in skin graft rejection. However, the effectiveness of Tregs combined with various immunosuppressive drugs used in transplantation remains unclear. My research aims to bridge this gap by investigating how engineered Tregs interact with common drugs to identify optimal combination therapies for transplant tolerance induction. I will also explore the underlying mechanisms of immune suppression. Ultimately, this work will inform the design of clinical trials, optimizing drug-Treg combinations as a therapeutic approach to combat transplant rejection.
In children, ongoing pain can interfere with brain development, disrupt behaviour and increase the risk of chronic pain. This can be particularly devastating in children with high burdens of pain, such as children with cancer, many of whom experience highly-distressing pain requiring opioids. Providing timely and adequate pain treatment for these children is critical, yet it remains challenging to predict who will experience pain requiring opioids and how these children will respond to prescribed opioids. This is especially difficult in young children who cannot articulate their level of pain, limiting their ability to receive appropriate relief without harm.
My research program is working to identify unique genetic signatures that predict how likely a child is to develop painful conditions, experience severe pain and respond to opioid-based pain relievers. This information will be used to develop predictive genetic tests to inform medication choices that will enhance the safety and effectiveness of pain management strategies for children. This work also has the power to combat the opioid crisis that continues to devastate British Columbians, where opioids can be restricted to patients most likely to benefit without harm.
Children with life-threatening illness need urgent, high-quality, hospital care. In BC, regions with the highest rates of child death are the furthest from specialized pediatric hospitals. Healthcare providers in local community hospitals initiate treatment for sick children. Children who need specialized care are transported to one of two pediatric intensive care units (PICU) in BC, in Vancouver and Victoria. Canadian research suggests needing transport to access PICU care could increase a sick child’s risk of dying. Inequitable access to care may lead to inequitable outcomes for children in our province. I propose to 1) Describe geographic differences in rates of life-threatening illness among children in BC, 2) Describe what happens to children with life-threatening illness in the hospital and after they go home, and 3) partner with patients, families, communities, and healthcare providers to evaluate health equity stratifiers that may be associated with a child’s risk of developing life-threatening illness or their outcome due to systemic inequity. Our research will improve understanding of the healthcare needs of sick children in BC and inform initiatives to ensure that all children have the best care and chance of recovery.
