Nurses often have stigmatizing attitudes towards people who use illicit substances that make it difficult for them to provide harm reduction services. This study will look at the state of harm reduction in an acute care hospital. Specifically it will examine the attitudes of acute care nurses towards addiction and harm reduction and whether they are willing to provide harm reduction services. The study hospital has recently changed its substance use policy which now directs nurses to provide clean needles. However, there is no evidence to indicate whether nurses have taken up this policy. The findings will help administrators and educators determine what support front line acute care nurses need to change their opinions about addiction and their preparation and willingness to provide harm reduction services.
Program: Trainee
Role of myelin pathology in vascular cognitive impairment
Vascular cognitive impairment (VCI) is caused by cerebral small vessel disease and is associated with cognitive and physical impairments in aging. Cerebral small vessel disease can lead to different types of brain damage, including myelin loss. Myelin is critical for proper brain function because it allows different brain regions to communicate with each other and intact myelin is vital for optimal human function. It is crucial for us to measure myelin loss and understand how myelin loss may be associated with cognitive and physical outcomes in older adults with VCI.
The goals of this study are to: 1) determine whether myelin loss is associated with cognitive and physical function in VCI and; 2) determine whether myelin imaging is better than other imaging techniques at assessing cognitive and physical outcomes in older adults with VCI.
The results of this study will: 1) help us understand how myelin loss affects cognitive and physical function and; 2) help us determine whether myelin imaging can be used as an additional tool to monitor disease progression and assess the efficacy of clinical intervention studies.
Genome-wide screen to identify genetic modulators of glucocerebrosidase activity
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Despite PD affecting millions of people worldwide, no disease-modifying treatment is available yet. As the progress of the disease is closely related to aging, improving our knowledge of the mechanisms and factors leading to PD is of great interest. Mutations in the gene GBA, which encodes the enzyme glucocerebrosidase (GCase), are the greatest genetic risk factor for PD. The link between GCase and PD however, remains poorly understood. Here, we propose to use a chemical genetic screening approach to identify new genes that affect GCase activity. As a pilot study, we will target known PD-associated genes and evaluate their effects on GCase activity using a new GCase activity-based assay in live cells. A complementary approach using genome-wide screen will be carried out to identify candidate genes in an unbiased way. Candidate genes from these screens will be validated with downstream experiments leading to two valuable outcomes. First, the discovery of new genes that regulate GCase could provide new targets for potential treatments. Second, we expect these findings will uncover new fundamental understanding regarding the mechanisms contributing to PD.
Connecting clinical research and economic evaluation by mapping lung function to EQ-5D-5L in patients with interstitial lung disease
Interstitial lung disease (ILD) is a group of diseases that cause inflammation and scarring of the lungs. It is important to identify ways to improve quality of life (QoL) for patients living with this chronic condition. This research will explore how QoL changes over time in ILD and identify factors that can potentially be modified to improve QoL.
Mycophenolate mofetil (MMF) and azathioprine (AZA) are two common medications used to treat certain ILDs and improve QoL. Despite MMF being better tolerated, only AZA is initially covered by PharmaCare in BC. This research will determine whether MMF is more cost-effective than AZA and could inform drug reimbursement policies.
Economic evaluations are used by funding agencies in Canada to determine whether a drug should be funded or not. However, economic evaluations for ILD drugs are limited because clinical trials do not provide the required information. This research will create an algorithm that allows economic evaluations to be completed even when these required data are not available. These economic evaluations can then be used to guide decisions on funding effective treatments in ILD.
The interplay between inflammatory bowel disease and Clostridioides difficile co-occurrence and the pediatric gastrointestinal microbiome
Gastrointestinal (GI) infection caused by the bacterium Clostridioides difficile is a common complication of inflammatory bowel disease (IBD), a condition caused by an aberrant host immune response to the GI microbiota. C. difficile infection (CDI) typically occurs after disruption of the GI microbiota, making the immune response to microbiota during IBD a major risk factor. This is particularly important in pediatric populations where 47% may suffer from an IBD-CDI co-occurrence. Fecal microbiota transplant (FMT) is a successful experimental treatment for IBD and CDI. It is thought to work by restoring a healthy-functioning microbiome to the IBD-CDI patient, however the specific host and bacterial factors that define FMT’s success remains unknown. We will recruit pediatric IBD-CDI patients to define host immune responses to FMT treatment. Using a novel IBD-CDI mouse model, we will then attribute host responses to FMT therapy and microbiota composition. This translational research will advance our mechanistic knowledge of FMT efficacy and ultimately impact FMT safety and governance. We will present our findings at international conferences including Canadian Digestive Diseases Week and aim to publish them in high-impact journals.
Refining the approach to Cystic Fibrosis Pulmonary Exacerbations – modelling data to improve assessment and predict etiology.
Cystic fibrosis (CF) is a rare hereditary condition where patients experience frequent chest illnesses (exacerbations), resulting in a decline in lung health and premature death. Typically, exacerbation symptoms include an increase in cough and phlegm, with an accompanying decline in lung function. Up to half of all persons with CF (PWCF) require at least one course of intravenous antibiotics to manage their exacerbations each year, but at least 25% will not recover to their original lung function after treatment. While it is clear that not all chest illnesses in PWCF occur due to bacterial infections, we are unable to identify other causes when diagnosing a patient. Consequently, PWCF receive antibiotics in almost all instances of chest illness, even when bacteria may not be the cause, exposing these patients to unnecessary harm. This study will involve analysis of blood and phlegm samples from >100 PWCF to identify clinical and molecular markers that can indicate the cause of an exacerbation. Through the use of sophisticated statistical techniques, we will then develop a tool that can be used to predict exacerbation cause and allow physicians to select treatments that are more specific, appropriate and beneficial for patients.
Targeted isolation and identification of N-N bond-containing bioactive molecules from bacteria
In the modern pharmaceutical industrial, a large number of new drug candidates come from molecules isolated from microbes. These “natural products” include some of our most powerful antibiotics, chemotherapeutics, and other medicines. Unfortunately, investment into natural-product drug discovery has declined since the turn of the century, owing to the high chance of re-discovery of known molecules. However, advances in bioinformatics suggest that the number of potential new drugs available from microbes is enormous. To advance the field of natural product drug discovery and exploit these advances in bioinformatics, we are developing a creative method to discover natural products with specific chemical sub-structures, which have a high probability to become drug candidates. This method is a biosynthetically-inspired, genome-mining technique that employs 15N-NMR as a key technique. Our initial work has resulted in a structurally unprecedented molecule, together with a yet-unknown molecule with exceptional antibiotic activity against gram-negative pathogens. Here we propose to extend our approach for the targeted isolation of additional molecules, followed by assessment of their pharmaceutical properties for preclinical testing.
From genes to ecology: The current and future distribution of arbovirus vectors in BC
Mosquitoes are the world’s deadliest animals due to the pathogens they spread and are often highly invasive. Arboviruses (arthropod-borne viruses) are spread by arthropods such as mosquitoes, and frequently infect both human and animal hosts. Multiple mosquito-vectored arboviruses have spread to new regions recently, including West Nile virus and Zika virus. While the mode of introduction is often unknown, the movement of infected mosquitoes or infected animal hosts are believed to be two of the methods responsible.
East Asia is an area from which arboviruses and mosquito vectors are at increasing risk of introduction to BC. I will survey the distribution of mosquitoes that vector established arboviruses in BC, or that could serve as vectors for arboviruses at risk of emerging in BC, particularly in northern and rural regions. I will use machine learning to model the distribution of these species now and in future climate change. What makes a mosquito species likely to be invasive will be studied using genomics, ecology, and cutting-edge behavioural techniques. Once these traits are known, I will model potential habitat in BC of candidate species from east Asia that could become invasive in BC.
A novel strategy to mitigate secondary hypoxic injury following traumatic spinal cord injury through the augmentation of local microvascular oxygen supply
There are approximately 2000 new cases of traumatic spinal cord injury (SCI) per year in Canada, with an associated health care cost of more than $1,500,000 per patient over a lifetime. The severity of SCI is compounded by injury processes that arise following initial trauma, which are related to a reduced oxygen supply to the injured spinal cord tissue. This process, where oxygen supply is reduced, is modifiable and therefore an ideal target for treatments aiming to improve outcome in SCI patients. Despite the potential to improve oxygen supply to the injured spinal cord, current treatments have yet to demonstrate notable efficacy. This is because it is difficult to alter oxygen supply to the spinal cord without causing undesirable changes in a patient’s blood pressure. We will utilize novel breathing strategies to target a specialized blood flow control mechanism to improve oxygen delivery to the injured spinal cord in rodent models of SCI. Further, we will characterize the function of this blood flow control mechanism in SCI patients, which will allow us to establish the potential efficacy of an exciting new avenue for improving outcomes and reducing healthcare burden after SCI.
Don’t let ILC3s take your breath away
Lungs are constantly exposed to environmental challenges, making them susceptible to infection and injury. For this reason, they are protected by specialized cells that can respond rapidly to danger signals. Amongst these cells are innate lymphoid cells (ILCs) that include three main subsets: group 1, group 2 and group 3 ILCs. To date, the majority of the studies have focused on ILC2s and their importance in allergy and tissue repair. However, it is now becoming evident that ILC3s play a key role in lung health. In fact, ILC3s have recently been shown to accumulate in the lung after Mycobacterium tuberculosis infection and in an obesity-induced asthma disease. Accordingly, preliminary results show that the accumulation of ILC3s in the lung is mediated by IL-1b, yet the mechanisms inducing ILC3s in the lung and their function remain unclear. This project will provide an extensive analysis of the origin and functions of ILC3s in naive and inflamed lungs, with an ultimate goal of translating our findings to a wide range of lung diseases, which are life-limiting and still a major cause of death in young, elderly, immune-compromised and cystic fibrosis patients.