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.

Patient-centered development of a research program on social robotics for pediatric anxiety

Co-lead:

  • Nadeen Jaik-Robinson
    Patient partner

Team members:

  • Jill Dosso
    UBC, BCCHRI
  • Jaina Jaik-Robinson
    Community member
  • Alessandra DiGiacomo
    UBC, BCCH
  • Anna Riminchan
    UBC, BCCHRI
  • Katarzyna Kabacinska
    UBC, BCCHRI

Could a social robot — a small robotic character or pet — be helpful to children living with anxiety? For this project, we will work with children and families to imagine the future of robotics for children’s mental health and learn about what useful social robotics for children could look like in British Columbia. Studies have shown that children are highly receptive to potential robotic interventions and are likely to be accepting of them as tools to improve their health. However, social robots are often developed according to engineer- and expert-driven priorities, rather than in consultation with end-user families.

In the proposed work, we will hold a series of three workshops with families with a lived experience of childhood anxiety in order to identify the most pressing research questions when it comes to pediatric mental health and social robotics. We will also learn from these families what outcomes are most important to them. The overall goal of this work is to understand what would make a robotic intervention helpful and meaningful to families.

Treatment of Pediatric Mental Health Problems: Unravelling the Role of Patient and Family Motivation in Eating Disorder Outcomes

My goal is to improve treatment for children and youth with eating disorders (ages 8-24 years). Eating disorders typically develop during adolescence. Eating disorders can become lifelong, and cause permanent health problems and even death. Making sure that each child gets the right kind of treatment can lead to the best outcomes. But, current guidelines do not consider how to match a child to the best type of treatment.

Knowing about motivation to change in children and families can help clinicians match a child to the best treatment. People who are motivated to change recognize there is a problem and are willing to work on this problem. Higher motivation leads to better eating disorder treatment outcomes in adults. Yet, motivation is not well-studied in youth. In fact, youth are often brought to treatment by their parents. So, parents’ motivation to help their child may be one of the most important features to measure.  

This project will tell us how youth and family motivation affect eating disorder outcomes. It will also tell us how clinicians use information about motivation. At the end of the project, I will be able to update guidelines about how to match a child to the best treatment.

The use of human stem cells to understand mechanisms and develop treatments for neurological disorders

Brain disorders are among the most significant health problems of modern day with enormous medical, social and economic burdens in British Columbia, Canada and globally. There is a substantial gap between the burden of brain disorders and the resources available to treat them. Neurodevelopmental disorders are particularly devastating, placing a heavy emotional and economic burden on children and their families. A major challenge in tackling these disorders is the inability to obtain and study brain cells directly. New technologies which allow stem cells to be transformed into brain cells are starting to help overcome this hurdle. 

By studying brain cells derived from human stem cells, Dr. Pouladi aims to

  1. understand how brain disorders develop and
  2. to identify new ways to treat them. A major focus of his studies are monogenic neurological disorders and in particular fragile X syndrome (FXS). FXS is the most common inherited form of intellectual disability and remains without effective treatments options. 

The stem cell-based discovery platform established and knowledge gained as part of Dr. Pouladi's program have the potential to advance therapeutic development for not only FXS, but also other neurodevelopmental disorders.

Optimizing post-procedural pain trajectories through patient-oriented research and artificial intelligence

Our goal is to use smartphones and artificial intelligence to improve pain management for children having surgery. This is needed because many children still have a lot of pain even a year after surgery. The pain affects their daily life, and might cause them to return to hospital. A child’s pain is affected by many things, like their biological sex, anxiety, coping skills, pain level, and type of surgery. Importantly, some of these can be altered.

We will collect data to identify patterns that predict which children

  1. do well after surgery, so we can learn from them or
  2. do not do well/have significant pain, so we can help sooner or even prevent it. We will involve families and children having surgery now, to collect data for a pain risk score to help future children.

We will design a tool to share pain risk data with families and doctors and test these tools in children coming to hospital for spine, tonsil or dental surgery. We hope that using these tools (pain prediction models) will improve the child’s individual care. Identifying children at high pain risk will allow us to intervene before their surgery. This will lead to quicker recovery, less time in hospital, and less chance of addiction to painkillers (opioids).

COVID-19 in children and young adults in BC – evaluation of public health measures and epidemiologic support for decision-makers

We do not know how many children and young adults have been infected with COVID-19 because they have milder symptoms and are usually not tested. For most infections children and young adults are important in spreading the infection. We urgently need to find out how much children and young adults have had the COVID-19 virus. The only way to do this is by testing a large number across the population. In this project we will collect saliva and blood from 6,000 people under 25 years and test for the COVID-19 virus and antibodies against the virus. We will send kits for people to collect these samples at home and then mail them to us. We will then know how many children and young adults have been infected, which will help make decisions about physical distancing and school closures.

Novel nanomedicines for resolving inflammation as a treatment for type 2 diabetes

This project proposes a new nanomedicine approach to treat type 2 diabetes (T2D). Studies in humans and mice have shown that inflammation in fat tissues and the pancreas is a major driving force for the development of obesity-induced insulin resistance and diabetes. A major limitation of current drugs is that they distribute over the entire body, exposing all cell types, while only a small amount reaches the desired target cells at disease sites, such as macrophages in inflamed tissues. This results in limited drug efficacy and unwanted side-effects. We aim to develop a new treatment for T2D that exploits the natural physiological processes to suppress inflammation in macrophages within fat tissues and the pancreas with high potency. We will use lipid nanoparticles (LNP), which are drug delivery systems customized to stably carry a large amount of drugs to macrophages.

Scientific development in this project will involve testing of LNP containing immune-modulating drugs in obese, diabetic mice, and measuring the anti-inflammatory and anti-diabetic effects. With close to half a billion people worldwide suffering from T2D, we believe that the proposed cell-specific treatment can have a significant impact on health and the economy.

Role of the Histone Acetyltransferases p300/CBP in Brown Adipose Tissue Adaptive Thermogenesis

Obesity is rising in Canada at an alarming rate, which is bad for our healthcare system because it results in diseases like heart attacks and diabetes. Although eating less and exercising more can reduce weight, these lifestyle changes can be difficult to maintain, prompting interest in finding ways to ramp up the calorie-burning processes in the body to promote weight loss. Brown adipose tissue (BAT) is a kind of fat that is found in both humans and mice. Unlike white adipose tissue, BAT is specialized for calorie burning rather than storage. We don't know exactly how the body controls how much BAT it makes, how it turns BAT on for burning energy to control body weight, or why some people lose their BAT with age.

One possible way these processes might be controlled is via proteins that 'open' and 'close' DNA within BAT to turn key calorie-burning genes on and off. Proteins that close DNA within BAT can worsen obesity by blocking BAT development, so the body can't burn as many calories. We are interested in how proteins that 'open' DNA (specifically, a pair called p300 and CBP) in BAT can influence energy expenditure.

To find out whether p300/CBP activate BAT calorie burning, we will induce obesity in mice that have p300/CBP working within their BAT, and in mice without these proteins. We expect mice missing p300/CBP will also have problems making BAT, so they will also be unable to burn energy using this tissue – resulting in the development of obesity and diabetes.