Univerity of British Columbia Archives

Reducing harms associated with ‘before medically advised’ hospital discharge

About 1 in 30 hospital patients leave the hospital before completing their treatment. These are known as ‘before medically advised’ (BMA) discharges. These patients are at a much higher risk of death, being readmitted to the hospital, or suffering from a drug overdose. Despite these risks, there are no established care guidelines for how to manage these patients, many of whom struggle with addictions and homelessness. To address this, the study will first examine whether the proportion of patients with BMA discharge has increased in Canada over the past 16 years. Next, the study will use data from British Columbia to explore whether proactive follow-up by a physician within 7 days of discharge can help reduce the risk of death, readmission, or overdose, compared to not having any follow-up. The goal is to create better care strategies for these vulnerable patients. The results will be shared with hospital staff, administrators, and the public to improve patient care.

Pushing musculoskeletal primary care to new frontiers: Musculoskeletal Comprehensive Assessment and Response in Emergency (MSK CARE) clinic in the Fraser Health Authority

The overall aim of this project is to address gaping holes in how musculoskeletal pain is served in BC emergency departments. We will develop and pilot the Musculoskeletal Comprehensive and Response in Emergency (MSK CARE) clinic in emergency departments in the Fraser Health Authority. This type of clinic diverts patients to a MSK practitioner for triage and management. Similar clinics are running successfully in Australia and Canada (Montréal, Quebec City, Kingston, Calgary, Sherbrooke). In BC, there are no similar clinics like the MSK CARE clinic, despite these types of clinics delivering “shorter wait times, happier patients and expert care.” We will measure whether the MSK CARE clinic can (1) reduce the amount of time patients spend waiting in emergency departments, 2) successfully re-direct (‘divert’) patients from the emergency departments, and (3) is an acceptable and feasible model of care. The findings will be shared through research publications, webinars, café scientifique, and infographics. The findings from this project can provide one solution to assist in tackling overcrowding in the Fraser Health emergency departments and improve access to primary care for all people with musculoskeletal pain in this region.

Blocking the tumour-promoting effects of Fusobacterium nucleatum by eliciting an effective immune response against the tumour-binding Fap2 lectin

This Health Research BC and GlycoNet co-funded project focuses on Fusobacterium nucleatum (Fn), an oral gram-negative, anaerobic bacterium that can spread in the blood to colonize colorectal adenocarcinomas and other cancer types. Fn is found in ~50% of colorectal tumors and is associated with chemoresistance, metastasis, recurrence, and generally poor patient outcomes. Our overarching hypothesis is that immune interventions against Fn can mitigate its tumorpromoting effects. Tumour colonization by Fn is mediated by Fap2, a large (400 kDa) lectin that binds to host cell GalGalNAc, over-expressed by CRC tumour cells. Our objective for this project is to create recombinant, truncated forms of Fap2 with native conformation, which will serve as immunogens for the generation of candidate vaccines and mAbs that will then be tested in murine challenge models. In future work, we will aim to advance promising candidates to academic clinical trials.

A Pathogen-ready Arsenal of Next-generation lipid nanoparticle (LNP) messenger RNA (mRNA) therapeutics

RNA-based genetic medicines have enormous potential to transform disease prevention and treatment. However, RNA molecules are very unstable, and the analytical methods available to assess them can’t accurately predict how effective a new genetic medicine will be. A lot of time and money is therefore spent on testing each RNA in labour-intensive functional experiments, slowing drug optimization efforts.

This project titled A Pathogen-ready Arsenal of Next-generation lipid nanoparticle (LNP) messenger RNA (mRNA) therapeutics (PAN-RNA) funded by Genome BC Immunoengineering Strategic Initiative aims to develop two new genetic medicines (for autoimmune disorders and cystic fibrosis), and a comprehensive analytical platform designed to accelerate their development and optimization. We will screen viral genomes to identify sequences that increase RNA stability and expression in specific target cell types, such as lung cells for the cystic fibrosis drug. We will then experimentally assess the functional performance of therapeutic RNAs that incorporate these viral elements. In parallel, we will use advanced imaging-based measurement techniques to comprehensively characterize genetic medicines containing different RNAs. Correlating the resulting data with our functional data on the same RNAs will allow us to develop sophisticated mathematical models that can predict the effectiveness of RNAs using our analytics methods alone, vastly reducing the amount of time and money spent on functional testing.

The immediate outcomes of the project will be two new candidate genetic medicines for further development, a validated analytics platform, and mathematical models to predict genetic medicine performance. However, our work will also serve as proof-of-concept that can be rapidly applied to the development of numerous other genetic medicines. These outcomes will help the biotechnology and pharmaceutical sectors accelerate their genetic medicine development pipelines, ultimately creating new medicines to fight pandemics and help Canadians living with autoimmune disorders, cystic fibrosis, cancer, and other diseases. Our work will also help create new Canadian biotechnology and pharmaceutical industry jobs, companies, and revenue streams, providing additional economic benefits.

The BC-based PAN-RNA project is led by UBC co-directors Eric Jan (Life Sciences Institute, Department of Biochemistry and Molecular Biology) and Sabrina Leslie (Michael Smith Laboratories, Department of Physics). PAN-RNA has assembled a team of expert leaders including Pieter Cullis, a world leader in LNP delivery technology and Laura Evgin, an ECR-expert in CAR-T therapies, Leonard Foster, a proteomics/mass spectrometry expert with extensive experience running a core platform, and collaborators Selena Sagan (molecular virologist), Sarah Hedtrich (lung epithelial gene therapy), Marco Marra (world leader in genomics), and Robin Coope (high-throughput instrumentation). The PAN-RNA project is co-funded by CIHR and NSERC.

SleepPOSAtive Trial: Positional Therapy for the Treatment of Positional Obstructive Sleep Apnea in Children

Dr. Lena Xiao, MD, MSc is a Pediatric Respirologist and Sleep Physician at British Columbia Children’s Hospital and Clinical Assistant Professor at the University of British Columbia. She received the IMPaCT and Michael Smith Health Research BC 2025 Training Award for early career researchers to develop a pan-Canadian multicenter clinical trial protocol evaluating positional therapy for the treatment of obstructive sleep apnea in children.

Obstructive sleep apnea causes recurrent upper airway blockage during sleep leading to low oxygen levels and unrefreshing sleep. Sleep apnea affects 1-5% of children and impacts physical, mental and psychosocial health. The main treatment is a surgery to remove the adenoids and tonsils, which are glands that block the nose and throat when swollen. However, many children still have sleep apnea after this surgery and will need to use a breathing machine called positive airway pressure therapy. The problem is that half of all children find breathing machines uncomfortable and cannot use them regularly. Other therapies called hypoglossal nerve stimulation, drug-induced sleep endoscopy directed surgery, and heated high flow are promising sleep apnea treatments but are expensive and hard to access. We need to identify cost-effective, simple, and comfortable alternative treatments that can help children with sleep apnea throughout Canada.

Many children with sleep apnea have more severe airway blockage when they sleep on their back called positional obstructive sleep apnea. A simple treatment could be a positional sleep belt, which is a chest-worn belt with cushions on the back to prevent a child from sleeping on their back. We are planning a randomized controlled trial across Canda evaluating whether positional therapy is more effective than beathing machines for treating positional obstructive sleep apnea in the home environment for children. This trial will provide important information about alternative therapies for sleep apnea in children.

From Bench to Bedside: Monitoring the Injured Spinal Cord with NIRS

A spinal cord injury diagnosis is life-changing for patients and their families. In acute care, beyond surgery and cardiovascular support, clinicians have limited tools to improve outcomes. Current guidelines recommend increasing blood pressure during the first three to seven days post-injury to enhance spinal cord blood flow. However, it remains unclear whether this approach improves oxygen delivery to the injured spinal cord or risks further damage at the injury site. To address this, we have developed a near-infrared spectroscopy (NIRS) sensor to measure oxygenation and blood flow to the injured spinal cord in real time. Implanted during spinal surgery, the sensor emits near-infrared light into the spinal cord, assessing oxygen delivery based on light absorption. This BC-based study, conducted at Vancouver General Hospital under the leadership of principal investigator Dr. Brian Kwon, aims to recruit six patients with acute spinal cord injuries undergoing surgical repair. The sensor will be implanted during surgery, remain in place for up to seven days post-injury, and then be removed. Our primary objectives are to evaluate the safety, feasibility, and effectiveness of this novel monitoring approach in a clinical setting. Ultimately, our goal is to provide clinicians with real-time information about spinal cord oxygenation and blood flow, enabling personalized care to improve patient outcomes.

Developing a multiplex serology assay for the detection of highly pathogenic influenza

Since 2021, North America has experienced devastating outbreaks of Highly Pathogenic Avian Influenza virus (HPAIV) driven by HPAIV H5N1 clade 2.3.4.4b. Recently, it has spilled over into dairy cattle in the USA, raising concerns about its adaptation to mammals and potential human spread. Wild birds are the natural carriers of avian influenza viruses (AIV), but H5N1 can also infect wild mammals. Current HPAIV surveillance programs sample dead wildlife and use molecular methods that only detect active infection, underestimating the true number and distribution of infected animals. Serological tools measure antibodies from previous exposure and not active infection. However, current serology assays are not specific for HPAIV H5N1, can only be used in a limited number of species, and/or are too complex for large-scale implementation. To address this challenge, the BC based leadership team (Dr. Agatha Jassem at UBC/BC Centre for Disease Control and Dr. Chelsea Himsworth at BC Ministry of Agriculture) will design a new assay to detect antibodies specific for AIV. The test will detect multiple subtypes in one sample and can be used on different animal species with confirmatory testing done at the Canadian Food Inspection Agency (Dr. Yohannes Berhane) and cross-validation at Public Health Ontario (Drs. Maan Hasso and Vanessa Tran). This research will generate a standardized test crucial for nationwide comparative analyses. Its species independent nature allows for easy use in domestic animals and humans as needed, providing crucial insights into antibody reactivity, cross-reactivity, and infection reservoirs.

Harmonized biomarkers to measure response to ustekinumab in type 1 diabetes

In type 1 diabetes (T1D), immune cells called T cells destroy insulin-producing beta cells, causing lifelong insulin dependence. Blood glucose control remains imperfect despite insulin injections, leading to an increased risk of complications from chronic hyperglycemia and a shortened lifespan. An antibody known as ustekinumab has been found to inhibit inflammation and can be safely administered to young adults with recent-onset T1D.

Our clinical trial, UST1D2, aims to test ustekinumab’s ability to halt progression of recent-onset T1D in young adults using patient samples collected from the BC Diabetes Clinic and the Mount Sinai Hospital in Toronto. This drug was previously demonstrated to decrease inflammatory proteins thought to damage beta cells, IFN-γ and IL- 17. Changes in inflammatory proteins and in the balance of immunoregulatory versus inflammatory cells may elucidate ustekinumab’s mechanism of action and biomarkers of response to therapy. The mechanistic studies will be conducted in Dr. Megan Levings’s lab at BC Children’s Hospital Research Institute, with Dana Lao, a Master of Science student at the University of British Columbia, acting as the lead trainee for the project.

To comprehensively evaluate mechanism and response biomarkers, the mechanistic studies carried out are harmonized between UST1D2 and another study called USTEKID that tests ustekinumab in children. This increases sample size, allowing for faster determination of treatment effectiveness. Our project contributes toward evaluating ustekinumab as a treatment for T1D patients and represents a new collaborative model to evaluate outcomes from international, multi-centre clinical trials.

This project is supported by the CANTRAIN-CTTP & Michael Smith Health Research BC 2024 Masters’ Studentship co-funded by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) and Michael Smith Health Research BC.

The effects of diesel exhaust air pollution exposure on inhaled corticosteroid treatment in late-onset asthmatic patients

With the advancement of global urbanization, the prevalence of air pollution continues to become of increasing concern for individuals worldwide. Asthma is a respiratory disease characterized by narrowing of the airways, leading to difficulty breathing. To manage symptoms, inhaled corticosteroids (ICS) are prescribed to reduce symptoms. However, studies have shown that exposure to air pollution, particularly in the form of diesel exhaust (DE), reduces the effectiveness of ICS, resulting in overprescription of the drug that can cause side-effects. To understand how DE exposure confers with ICS efficacy, I, Michael Yoon, alongside members of the Air Pollution Exposure Lab (APEL; https://www.pollutionlab.com/) will be conducting a controlled human exposure study where asthmatic participants will be exposed to regulated levels of DE. Through this study, we will be able to understand the biological changes associated with reduced ICS effectiveness for improved treatment.

This BC-based project has been funded by the Canadian Consortium of Clinical Trial Training Platform-Clinical Trials Training Program (CANTRAIN-CTTP) & Michael Smith Health Research BC Doctoral Studentship 2024 Award Program as well as the Canadian Institutes of Health Research (CIHR) organization. The primary goal of the proposed project is to determine how DE interferes with ICS treatment, where our aim is to translate our findings to improve current health policies regarding ICS administration, resulting in safer usage.

Targeting Lipid Nanoparticles (LNPs) to Antigen-Presenting Cells Through Siglecs to Improve Vaccine Response and Durability

Vaccines can provide both short-term and long-term protection from deadly pathogens. This was demonstrated during the COVID19 pandemic, which saw the rapid production of lipid nanoparticle (LNP) mRNA vaccines. LNP-based mRNA vaccines are easy to produce in large quantities with a great degree of quality control on a relatively short time scale. These vaccines generally rely on passive uptake by antigen-presenting cells (APCs) to initiate priming of B and T cells, which are both required for a robust humoral (antibody) response. While LNP-based mRNA vaccines induce robust antibody responses, there are still questions about the durability of the immunological memory induced by these vaccines. Such a factor is a critical feature of a vaccine that keeps people protected over the course of years to decades. In contrast, many pathogens and viruses are actively taken up by glycan-binding proteins expressed on our immune cells that recognize host-derived glycans. Therefore, passive uptake of LNP-based mRNA vaccines misses out on this natural route of uptake. We hypothesize that targeting LNPs to immune cells, particularly APCs, may help improve the efficacy of vaccines. To do so, we will target sialic acid binding immunoglobulin-type lectins (Siglecs) that are carbohydrate-binding cell surface receptors found on immune cells. Siglecs are an ideal target for delivery because of their endocytic properties, their selective expression on immune cell subsets, and the availability of high affinity and selective glycan ligands for targeting. Here, we propose three aims to test this main hypothesis. In Aim 1, we will synthesize next-generation carbohydrate-based Siglec ligands for improved targeting. In Aim 2, we will formulate LNPs with ligands targeting Siglec-1, Siglec-3 (CD33), or Siglec-7/E to direct LNPs to macrophages, monocytes, and dendritic cells, respectively. Successful targeting will result in enhanced uptake of LNPs and increased expression of encapsulated mRNA in the cell type of interest. In Aim 3, we will examine the ability of Siglec-targeted LNPs to induce robust primary antibody responses directed at the spike protein of SARS-CoV-2, as well as memory responses following a boost. In summary, this project will develop Siglec-targeted LNPs to enhance immune responses as an improved vaccination approach.