Our focus is on the cellular fuels and building blocks that change immune cell functions. Our immune system normally defends us against infections. In a healthy person, T cells (a type of immune cell) recognize infected or cancerous cells and remove them from the body. Normally, immune cells know the difference between healthy and infected or cancerous tissues. When this recognition is lost, it can lead to the development of attack of healthy tissues by immune cells (autoimmunity), the growth of cancer, or to persistent infections. This dysfunction of the immune system can lead to devastating diseases in children. My research aims to better understand how this happens. By comparing the way that biological fuels (sugars, fats and other building blocks) are used by immune cells from healthy people and patients with immune system associated diseases, we will define the cellular the pathways that maintain health or cause disease. This will allow us to target and “dial down” pathways that are driving cells to attack our tissues, or turn these pathways on to help immune cells fight persistent infections and cancerous cells. Ultimately, we hope to help develop new treatments.
Research Location: BC Children's Hospital Research Institute
Genomic mechanisms underlying the prenatal and early childhood origins of mental illness in children
The last decade has seen an explosion of genomic and health-related data. These data can advance precision medicine, but only if we apply the right analyses. I use statistical methods that link together many different types of large genomic and health datasets. My research identifies genomic mechanisms that lead to disease, which is the first step towards improving patient care. A primary goal of my research is to learn about the genes that cause mental illnesses like attention-deficit / hyperactivity disorder (ADHD) in children. We know that genes are important to ADHD risk. We also know that babies born small are at increased risk of ADHD, and that the placenta influences a baby’s growth in the womb. What we do not know, however, is how genes that are important to placenta function also affect a baby’s future risk of ADHD. Answers to this question will help us understand ADHD biology so that we can develop better prevention and treatment strategies and give all children the best start in life.
Improving clinical practice guidelines for antenatal corticosteroids: Incorporating a decision support tool to impact clinical counselling
Antenatal corticosteroids are a medication given to women who are at risk of an early delivery to reduce the chance of breathing problems for their baby after birth. Current guidelines recommend giving antenatal corticosteroids to pregnant women who might have their baby before 34 weeks of pregnancy. This medication may also help those at risk of an early delivery at 34-36 weeks of pregnancy but the balance between the benefits and harms of this treatment is less clear at these ages. Guidelines for giving this medication at 34-36 weeks of pregnancy are also unclear, making it difficult for doctors and patients to decide whether to use it. We will find out if including a decision support tool in clinical guidelines will improve how doctors discuss antenatal corticosteroids with patients at 34-36 weeks of pregnancy. We will ask patients whether they had better discussions with their doctor about this treatment after their doctor had access to the decision support tool within the clinical guideline, and we will ask doctors how this decision support tool impacted their counselling. This project could improve communication between doctors and patients, especially when it is unclear whether a treatment’s benefits outweigh its harms.
Advanced pulmonary diagnostics in paediatric respiratory medicine: From technical development to clinical implementation
Chronic lung diseases present a serious health challenge for Canadian children and youth. For example, cystic fibrosis (CF) shortens life expectancy and carries an enormous treatment cost (>$250,000 per person per year). Another example is asthma, which affects nearly 1 in 7 Canadians under age 20. Improving the lives of people with these conditions is possible but requires accurate detection and close monitoring of their lung disease.
Unfortunately, the tests available to paediatric respiratory physicians are often difficult for children to perform and not sensitive enough to detect or subtle disease. This significantly limits physicians’ ability to detect, treat and monitor lung disease in children and must change.
My research program focuses on the development of easy-to-perform and sensitive tools to help physicians diagnose and monitor lung disease in children. Specifically, I am an expert in techniques known as hyperpolarised xenon lung MRI (XeMRI) and multiple breath washout testing (MBW).
During tenure of this Health Professional-Investigator award, I will lead research focused on improving the XeMRI and MBW techniques and using these new tools clinically to improve the health of children with lung diseases.
Outdoor early childhood education summit: Pathways to licensing in BC
Research on outdoor early childhood education (ECE) indicates vast benefits to children’s health, development, and learning. Further, outdoor ECE helps solve challenges related to provision of universal childcare and managing COVID-19 transmission. It enables an equitable childcare solution that embraces land-based learning and Indigenous ways of being. Yet BC licenses only indoor facility-based care. We will plan a summit aiming to bring together researchers and research users, including practitioners, licensing officers and policymakers from the BC Government, health authorities, and Indigenous communities to collectively identify priorities to support a pathway to licensing outdoor ECE in BC. Key outcomes will include: 1) To embrace elements of nature-based education — in particular, those having to do with risky play and land-based learning; 2) To identify key research and practice priorities collectively to enable legislative changes for regulating outdoor ECE programs; 3) To co-create products that support KT of summit outcomes for outreach to diverse groups; 4) To strengthen relationships and partnerships among key stakeholders to facilitate collaboration beyond the proposed summit.
Team members: Shelley McClure (Northern Lights College); Rachel Ramsden (UBC); Iris Berger (UBC); Enid Elliot (Camosun College, Early Learning and Care); Glynnis Schwan (Island Health and Community Care Facilities Licensing); Lily Patzer (Aboriginal Head Start Association of BC); Belva Stone (Muddy Boot Prints Outdoor Learning Program); Hartley Banack (UNBC); Kailee Hirsche (UBC)
Creating a partnership for obstetrical health services research in BC
Childbirth is the most common reason for a hospital visit in BC, accounting for 1 in 10 hospital visits. To make sure that pregnant women receive the best care possible, we need to evaluate how the way in which we provide care — our obstetrical policies and practices — affects the health of women and newborns.
BC has all the building blocks needed for world-class obstetrical care research — including a large database with detailed pregnancy records, university experts in policy analysis, and a single academic department of Obstetrics & Gynaecology. However, we have no mechanism for bringing these assets together.
This award will catalyze the creation of a partnership that brings together BC’s expertise and resources for evaluating obstetrical care. Key outcomes are to:
- Establish procedures for a working partnership of researchers, health care providers, and patient partners interested in conducting research to improve obstetrical care in BC, learning from partnerships in other fields.
- Bring together partnership members to co-identify research priorities for improving obstetrical health care in BC.
- Give students an opportunity to engage with care providers, patient partners, and experienced researchers.
Team members: Jessica Liauw (UBC); Ellen Giesbrecht (Perinatal Services BC); Julie van Schalkwyk (BC Women’s Hospital); Ken Lim (BC Women’s Hospital); Chantal Mayer (PHSA); Jason Burrows (Surrey Memorial Hospital); Sheona Mitchell (University Hospital of Northern BC); Raz Moola (Kootenay Lake Hospital); Luc Beaudet (Cowichan District Hospital); Val Rychel (St. Paul’s Hospital); Gillian Hanley (UBC); Laura Schummers (UBC); Charles Litwin (UBC); Amy Hobbs (UBC); Kenny Der (Perinatal Services BC)
Collaborating with Indigenous northern communities to develop a SmartMom prenatal education texting program for teens
Teenage pregnancy is associated with a higher risk of poverty, mental health problems, and substance use. In the Northern Health Authority, rates of teen births are twice as high as elsewhere in BC. Prenatal education is known to reduce unhealthy pregnancy outcomes, but few women attend in the north and the number of teens that attend is unknown. As an alternative, we have developed a prenatal education program, (SmartMom), that delivers three SMS text messages each week related to participants’ week of pregnancy. Over one year, we will engage and convene partners in Northern Health to develop a supplemental stream of messages that is relevant and engaging for teen mothers. Through two information gathering meetings in each of several communities, we will develop content that is age-appropriate and appealing to young mothers. We will also develop a Youth Advisory Council to review our messaging and plan evaluation activities. We plan to monitor teen participation in the program and measure changes in knowledge, adoption of healthy behaviours and rates of adverse pregnancy outcomes. While the primary focus is not Indigenous health, we aim to ensure Indigenous teens and their unique lived experiences are considered in our program.
Team members: Randi Parsons (Northern Health); Shaina Pennington (UBC); Vanessa Salmons (Northern Health); Jennifer Murray (UBC)
Evaluating the safety, efficacy, effectiveness, and immunogenicity of meningococcal vaccines across the age spectrum
Meningitis is a serious inflammation of the lining surrounding the brain and spinal cord, caused by viral or bacterial infections. One in ten people who develop meningitis will die, and 20% will experience serious, lifelong consequences, such as hearing loss or brain damage. The World Health Organization (WHO) has called for full prevention and control of this disease by 2030. Our team is collaborating with the WHO to develop evidence-based immunization strategies for this initiative. My research project will pool data from all previous vaccine studies on meningococcal group B (MenB), to assess the safety and protective effect of different MenB vaccines. Our goal is to use that data to answer questions such as, “How safe current meningococcal group B vaccines are?”; “How long they can protect us from getting the disease?”, and “How many doses are needed and on which schedule?”. Findings from this research will guide WHO strategies on dosing and timing of vaccines, to eradicate meningitis by 2030.
Developing the next generation of therapeutic regulatory T cells using CRISPR/Cas9
The immune system is critical for fighting infections but left unchecked, can attack healthy tissues resulting in autoimmunity or transplant rejection. Regulatory T cells (Tregs) are the immune cells responsible for controlling immune responses, so Treg transfusions are being investigated as treatments for these conditions. Unlike immunosuppressive drugs, Tregs are customisable and can have long-lasting effects.
Tailoring Tregs to treat specific diseases typically involves genetically modifying the cells. One approach involves incorporating synthetic proteins called chimeric antigen receptors (CARs) to help the Tregs migrate to where they are required in the body and specifically suppress harmful targets. I will build on this approach and explore the potential of using novel precise gene editing techniques (CRISPR) to maximise the survival and function of CAR Tregs following infusion.
This work will inform ongoing clinical studies that are investigating CAR Treg therapy in kidney transplantation, as well as future studies with other diseases. Fine-tuning personalised Treg therapy is key for its wide-scale implementation and potential to transform the life quality of autoimmune disease patients and transplant recipients.
Smart discharges to improve post-discharge survival in young infants following admission for infection
In many resource-limited countries, children who suffer from severe illness are at a high risk of dying in the six months after leaving the hospital. Most caregivers are unaware of this, although simple strategies like follow-up visits and healthy practices at home can improve survival. Our team has developed a tool that allows healthcare workers to identify children who are most at risk of dying after leaving the hospital. Healthcare workers can use this tool to identify the highest-risk children and plan follow-up visits, reducing the burden on families and the health system. The caregivers of all discharged children receive education on healthy practices and on the signs that their child needs follow-up care. In Uganda, our approach has saved the lives of children aged six months to five years old.
Here, we will confirm that this same approach can be used in a wider population. We will talk to families and healthcare workers to determine how best use this approach in different age groups and locations. We will work closely with our Ugandan partners to ensure improvements are long-lasting. Ultimately, we plan to work with our local partners to apply our approach and improve child health in remote communities across BC.