Co-developing knowledge translation tools to enable rapid mobilization of vaccine research to policy in BC

As BC strengthens its immunization policies and programs to respond to the challenges and learnings from the pandemic as well as health needs of British Columbians, it is essential for research to be a central pillar of decision-making. This project will co-develop, test and disseminate knowledge translation (KT) tools to support seamless integration of research into immunization policy and program implementation in BC. During phase 1, we will conduct an environmental scan to address the knowledge gap on effective KT strategies for moving research into evidence-informed policies and programs. During phase 2, researchers and research users will be invited to participate in a forum to inform the design of the KT tools. The tools will include knowledge product templates (e.g. policy briefs) and a guide to orient researchers to the immunization policy and implementation landscape in BC. Additionally, they will provide an overview of effective KT strategies and appropriate policy and implementation target audiences for disseminating a variety of vaccine research. During the final phase, we will design and disseminate the KT tools through workshops, webinars and social media. We will evaluate the process and impact of the new tools.

Team members: Monika Naus (BC Centre for Disease Control); Gabrielle Gaultier (UBC); Julie Bettinger (UBC); Bonnie Henry (Ministry of Health); Susan Hollenberg (UBC); Bryce Wong (BC Pharmacy Association).

Smart Discharges for Mom+Baby: Saving mother-newborn dyads by developing a predictive risk model to identify vulnerable dyads and guide delivery of post-discharge care

The risk of a mother or baby dying is highest in the first six weeks after birth. The World Health Organization (WHO) recommends regular follow-up visits for all mothers and their newborns. This is not always possible. In resource-constrained countries, a lack of money and nurses at hospitals and limited time and money at home often stops mothers from seeking care. In our study, we will build a score to identify mother-baby pairs that are most at risk of getting sick or dying in Uganda. The health of a mother impacts the health of their baby, and vice versa. Our risk score combines the risk of the mother and baby so that both can get care when they need it. A nurse can use this score to guide the number of follow-up visits recommended for the pair. In this way, mothers and babies at higher risk receive more visits. We will also talk to parents and nurses to determine what stops mothers and babies from receiving a follow-up visit. We will work with our Ugandan partners to remove these barriers so that improvements in care are long-lasting. In the future, we can use this approach to improve the health of mothers and babies in smaller, remote towns in BC, where specialized care for mothers and babies is not always readily available.

Defining optimal pregnancy weight gain ranges for Canadian women

Maternal weight gain is closely monitored during pregnancy because as weight gain increases, so does the risk of excess postpartum weight retention, diabetes, and high blood pressure. While lower weight gain may prevent these complications, it also increases the risk of poor fetal growth and stillbirth. Pregnancy weight gain recommendations that balance these risks are important. The goal of this project is to establish the optimal range of pregnancy weight gain for Canadian women. We will use existing medical records from approximately 560,000 women who delivered in BC between 2004 and 2018. We will obtain information on pregnancy weight gain, and link this with short- and longer-term health complications for mother and newborn, such as excess postpartum weight retention, maternal diabetes and heart disease, poor fetal growth, and stillbirth. We will use statistical models that enable us to consider all health complications at the same time, while accounting for the fact that some complications are more serious than others. Our findings could provide the basis for new public health recommendations on pregnancy weight gain, which could help to reduce overweight and obesity in Canadian mothers and their children.

Examining stress mediated profibrotic response in HCM associated TNNT2 variants

The heart beats 100,000 times a day, and cardiac contractile proteins are essential to facilitate oxygen-rich blood circulation. Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that promotes enlargement of the heart and fibrotic scars, leading to arrhythmias and sudden cardiac death (SCD). In Canada, all age groups are affected by HCM, especially children and youth, including elite athletes. The cardiac troponin T (TNNT2) gene variants account for 15 to 20 percent of HCM in humans. TNNT2 mutations can cause increased cardiac contractility and impaired heart relaxation, leading to structural remodelling and triggering arrhythmias and SCD. Currently, no specific medication is available to treat HCM patients. Previously, mouse or rabbit heart muscle cells were used for studying these TNNT2 mutations, which is not closely relevant to human physiology. Therefore, I aim to test TNNT2 mutants in human induced pluripotent stem cell-derived heart muscle cells (hiPSC-CMs) with different physiological and pathological stress conditions compared to normal hiPSC-CMs. Our research outcome will help us refine the profibrotic mechanism behind arrhythmias and SCD in HCM patients and timely intervention to manage patient care better.

Regulation of anabolic metabolism in anti-tumour T cells

Our immune system protects of our body by detecting and destroying cells that are potentially cancerous. Sometimes, our immune system fails to detect a problem, leading to cancer. In pediatric cancer, CD8 T cells fail to destroy cancer cells. CD8 T cells are white blood cells specialized in the detection and attack of cancer cells. Like us, CD8 T cells need to “eat” to stay alive, to move, and to function. Without nutrients, they can’t fight off cancerous cells. In cancer, there is a fight for nutrients between CD8 T cells and cancer cells. CD8 T cells have to quickly adapt to make sure they can maintain their protective functions. We know that CD8 T cells can rapidly switch from using nutrients to grow, to burning them to make energy, but we do not know how it is regulated. The aim of my project is to study how CD8 T cells know which nutrients are around them, and how they “choose” to switch between growing and burning. Why is it important? If we grow CD8 T cells in a laboratory setting, restrict their food, and re-feed them, they provide better protection against cancer. Understanding how CD8 T cells “eat” and use nutrients to grow or burn energy to kill cancer cells will help develop better therapies to treat pediatric cancer.

The links between nutrient sensing, cell intrinsic metabolism and T cell function in immune-related diseases

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.

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)