Spinal cord injury (SCI) not just causes paralysis but also more devastating issues such as impaired blood pressure (BP) and heart rate regulation, which are among the leading causes of illness and death among this population. The individuals with SCI above the mid-thoracic level commonly suffer from highly labile BP that rapidly reaches alarmingly high and low levels within the same day. These extreme BP fluctuations often result in seizures, ruptured brain blood vessels and even death. Hence it is not surprising that the individuals with SCI rank improving heart and blood vessel function among the highest priorities for recovery, even higher than regaining the ability to walk again.
The goal of this proposal is to test the potential of non-invasive spinal cord stimulation (delivered through skin) to promote blood pressure control in a rat model of SCI. Our laboratory's pilot experiments have already demonstrated that non-invasive stimulation is feasible and effective in humans with SCI. Present proposal will allow us to thoroughly understand the underlying mechanisms and enable widespread clinical use of spinal cord stimulation in improving quality of life of individuals with SCI.
Over 400,000 Canadians live with long-term disability from stroke. Stroke survivors say regaining walking ability is a top priority; but, poor cognition, or thinking abilities, can limit walking in the community. How much walking recovery someone achieves likely stems from the brain's ability to dual-task (DT), like walking while talking. In fact, almost 80% of stroke survivors struggle with some aspect of cognition limiting full walking recovery after stroke. The complex demands of community mobility after stroke can be studied in laboratory settings using DT, where walking is done with a cognitive task.
Using DT, studies have found the brain is crucial for DT, and that altered levels of brain activity affect DT ability. But, little research probes if stroke survivors could produce brain recovery with DT training, as neuroimaging methods like functional MRI, cannot collect data during standing and walking. Functional near-infrared spectroscopy (fNIRS) is an ideal imaging tool to assess walking without physical limits, but its utility to detect if DT training can drive the brain to recover walking has not been tested in stroke survivors. So, the goal of our clinical trial is to test if DT training can help the brain recover and allow for better DT ability. DT training may drive brain recovery by addressing cognitive and motor difficulties at the same time, maximizing rehabilitation efforts, and improve walking ability in the community after stroke.
Stroke is the leading cause of disability in Canada with more than 400,000 Canadians living with long-term disorders due to stroke. Hence, whilst challenging, it is critical to restore mobility to these individuals such as independent walking; the most frequently stated goal of individuals post-stroke. However, achieving this goal is hindered by motor impairments, including muscle weakness and spasticity, yet we still do not understand how these impairments influence walking post-stroke. This lessens the efficacy of emerging innovative treatments such as the use of botulinum toxin or Botox to suppress spasticity and improve walking. Computer simulations are powerful tools to uncover how muscles coordinate movement and predict the functional gains following a personalised treatment plan.
This research aims to develop diagnostic tools that can be used in clinical practice to identify movement deficiencies during walking post-stroke and associate them with clinical measures of function and spasticity before and after an intervention. These tools will facilitate greater use of personalised therapies, one of the primary goals of stroke recovery in Canada, and ultimately give people with strokes the ability to walk independently.
The cerebellum is a complex region of our brain involved in the coordination of our movements and cognition. Evidence shows that cerebellum is involved in several brain disorders such as ataxia (inability to move properly), autism, and medulloblastoma (the most prevalent brain tumor in children). The cerebellum is made of different cell types. Among them, the most numerous cell type, the granule cells, contribute to many crucial cerebellar functions. Indeed, an uncontrolled division of granule cells results in the most common form of pediatric brain tumor, the medulloblastoma. To understand the basis of cerebellum-related diseases and finding effective treatments, we need to study cerebellar development.
In my project, I will study the role of special regulatory molecules called microRNAs, which control gene activity in the developing cerebellum. Using modern cellular, molecular, and computational techniques, I will find a subset of microRNA molecules and their partner genes, which contribute to the normal development of granule cells in the developing cerebellum. Results of this work will provide useful and basic knowledge for scientists who study disorders of the brain, which have their roots in cerebellum development.
Breathing discomfort is common in patients with interstitial lung disease (ILD) and often results in an inability to perform physical activity, leading to a poor quality of life. Exercise training can reduce breathing discomfort and enable ILD patients to perform physical activity. However, severe breathing discomfort makes it challenging for these patients to withstand the amount of training they need to get the most benefit. A recent study showed that ILD patients breathing supplemental oxygen had less breathing discomfort and were able to exercise for longer compared to breathing room air. Another study showed that breathing supplemental oxygen was safe for patients with ILD for a single exercise session. However, we still do not know if these findings can be applied to a long-term exercise program.
Therefore, the purpose of this study is to determine if using a higher amount of oxygen during a rehabilitation program is a safe intervention that translates to greater benefits from training compared to the same regimen without the additional oxygen. We are also interested in examining if higher intensity training sessions with added oxygen affects every day physical activity levels.
Asthma is a serious public health issue in Canada and in the world, affecting more than 300 million people globally. To date, clinical trials have established that current treatment strategies for asthma can relieve patient symptoms, but none are able to reverse the disease process. It is known that in asthmatic lungs, the airways -tubes that allow air to flow in and out of the lungs for breathing – are continually injured and scarred in a process called fibrosis. The smallest airways in the asthmatic lung are the main sites of fibrosis and thought to have the greatest contribution to disease symptoms; however, current methods used to assess asthma are unable to provide information on the smallest airways.
Assessing these smaller airways could provide new ways to develop drugs to resolve the scarring that occurs in asthma. In this project, we will use new, more powerful imaging methods to determine the contribution of the small airways scarring in asthma and to identify the genes involved in this process. We will then develop laboratory models of the disease using patient lung cells that may be used in the future to develop new drugs to target the genes involved and resolve the scarring and blockade in the airways of asthmatic patients. The potential new drugs that will be found in this research will help to relieve the burden of asthma in BC.
Patients receive heart transplants as a life-saving measure after heart failure; thus, ensuring the success of the transplant is of utmost importance. Rejection is a primary cause for heart transplant failure, and consequently, heart transplants are monitored at least 12 to 15 times within the first year of operation. However, current monitoring requires biopsies, a surgical procedure which requires repeated sampling of the heart muscle. This procedure is invasive, expensive, and stressful to patients. Replacing the biopsy with a simple blood test can greatly improve patient quality of care and reduce healthcare costs.
Therefore, my goal is to develop a new blood test to monitor rejection following heart transplants. Using sophisticated computer algorithms, our group discovered molecules in the blood that can discriminate between patients who have rejected their heart transplants and those who have not. My goal is to develop a blood test to precisely measure these molecules. Also, I will study these molecules for their biological role in heart rejection process by examining immune cells and damaged heart cells found in biopsies. Accomplishing these research goals will produce a valuable clinical tool that can diagnose rejection in a fast, accurate, cost-effective, and minimally invasive manner.
Sepsis is a severe disorder that occurs when human defense cells fight off an infection in an uncontrolled manner that can cause organ damage and death. Unfortunately, there is no specific treatment for sepsis, and there is a limited understanding of the mechanisms driving this deadly disorder.
During infection, toxins are released in the blood and carried inside cholesterol particles, which are removed from the blood by the liver. People with decreased levels of PCSK9 (proprotein convertase subtilisin/kexin type 9), a protein that normally regulates cholesterol particle levels, seem to have an increased ability to clear toxins from their blood. This project aims to test if inhibiting PCSK9 increases the removal of toxins from blood during sepsis and reduces organ damage and mortality. The findings of this research can lead to improved understanding and management of sepsis, and potentially a new treatment for sepsis that could save thousands of lives every year in the future.
The drug overdose crisis has been hardest felt in BC. Research has shown that gender plays a key role in shaping contexts of drug use (e.g., within sex work, intimate partnerships) and access to treatment and harm reduction services. Women access treatment with more severe drug-related profiles relative to men (e.g. violence/trauma), yet few services are women-centred. New Vancouver Coastal Health guidelines highlight grave gaps in supports and prevention for marginalized women, and several new models of care are being rolled out (e.g., women-only consumption rooms). Several randomized clinical trials (RCTs) are underway in BC to increase access to evidence-based treatments.
However, the gendered impacts of these interventions remain poorly understood and under-investigated. The proposed research will evaluate the impacts of 'naturally occurring' and clinical interventions (i.e., through prospective methods and RCTs) using a gender lens to identify gender differences in treatment outcomes and barriers to accessing services. Research findings will be widely disseminated with the aim of informing gender-specific policies and programs for people who use drugs in BC and beyond.
People with or approaching kidney failure requiring dialysis often develop protein-energy wasting (PEW), which is characterized by loss of body stores of protein and energy fuels, and is associated with increased risk of death, heart disease, infections, and poor quality of life. The extent of PEW, its consequences, and its management have not been previously characterized among kidney patients in Canada, yet nutritional management remains a top research priority from the patient perspective.
Utilizing an existing database of chronic kidney disease patients in BC, the aims of the proposed study are:
- to determine the number and characteristics of adult kidney patients with PEW in BC, using several nutritional parameters and their changes over time to define PEW;
- to assess the impact of PEW treatment with nutritional supplementation (according to the BC Renal Nutritional Supplement Policy) on outcomes, including death, hospitalizations, nutritional lab parameters, and patient-reported functional status.
This research will:
- identify patients at risk of adverse outcomes from PEW in order to improve treatment policy and resource allocation, and
- inform future studies of dietary/self-management strategies for kidney patients