Program: Trainee

30% of stroke survivors will have another stroke. To prevent this, we can try to change several factors. These factors include high blood pressure (the most important factor), high blood sugar and fat levels, poor diet and mood, and smoking. Exercise can lower blood pressure, blood sugar and fat levels and improve one’s mood. Lifestyle-management education can improve one’s diet and mood and help stop smoking. However, we do not know if exercise and education programs can lower blood pressure and prevent another stroke in stroke survivors after rehabilitation. This study will test if an exercise and education program will lower blood pressure in stroke survivors compared to education alone. Stroke survivors recently finishing rehabilitation will be assigned by chance to one of two groups. The first group will complete an 8-week exercise and education program. The second group will only complete the education program. We anticipate that stroke survivors will have lower blood pressure after completing the exercise and education program compared to education alone. This will be one of the first studies in British Columbia to test if formal exercise and education programs after rehabilitation will help prevent another stroke.

Advanced cancer and its treatment can lead to physical function declines and disability. Physical function is the ability to perform activities of daily living and patients with advanced cancer describe that addressing losses in physical function is a top care priority. Cancer rehabilitation is designed to improve physical function, yet available services are underutilized by patients with advanced cancer. Poor patient and healthcare provider (HCP) communication and ineffective shared decision making about rehabilitation are key reasons for this care gap. Decision aids (DAs) are tools that enhance shared decision making, so patients know the decision to be made, understand options and outcomes, and have clarity on their personal values. Currently, a DA for cancer rehabilitation does not exist. The proposed research will develop a DA for cancer rehabilitation by determining patient decision support needs, designing a DA prototype, and evaluating the DA’s usability. The DA is a simple and low-cost tool that may improve patient and HCP communication about cancer rehabilitation, so that the top care priorities of patients with advanced cancer are better addressed within the current healthcare system.

Nontuberculous mycobacteria (NTM) are a group of environmental bacteria, commonly found in the water and soil. Many species of NTM – such as Mycobacterium avium complex – can cause chronic lung infections, which are difficult to treat and often associated with progressive lung damage. The number of people affected by NTM lung disease has been increasing around the world, however, we do not have a good understanding of its local impact. In this project, we will use province-wide data to characterize the scope of NTM lung disease in British Columbia (BC) and examine treatment patterns. We will also assess challenges associated with treatment, including early treatment discontinuation and bacterial resistance to antibiotics. Findings from this study will improve our understanding of the patient population affected by NTM lung disease in BC and inform efforts to improve the care of these patients.

With current treatment options patients with Osteosarcoma have a 5-year survival rate of about 76%, but for 3 out of 4 patients diagnosed with Osteosarcoma that has spread beyond the primary site will not live 5 years passed their diagnosis. There is clearly an unmet clinical need to develop new options for these patients. Immunotherapy aims to notify your body of the malignant cells and target them for destruction by the patient’s own immune system, however, its success in pediatric cancers is still lacking. One crucial aspect of developing successful immunotherapies is having a good target, and these are often targets that sit on the outside surface of the cancer cells. Our team has already characterized this area in Osteosarcoma and found a protein, TMEM119, to be extremely specific to Osteosarcoma. We have demonstrated that TMEM119 is not expressed in normal tissues, only in some sarcomas, making it an ideal strategy to target, but more work is needed. With this project, we aim to understand the role of TMEM119 in Osteosarcoma by selectively switching it off and examining whether this can prevent the spread of Osteosarcoma. We hope that our work can contribute to the development of a new strategy for Osteosarcoma patients.

Microglia are the immune defense cells located within the brain and also play a big role in the maintenance of a healthy brain by scavenging and removal of damaged/unnecessary neurons and synapses. This “synaptic pruning” function is important for the proper developmental wiring of the brain. Huntington’s disease is a disorder of the brain, which gets worse over time. It is caused by DNA repeat expansions in Huntingtin gene leading to neuron cell toxicity and death. Of late, the role of microglia in Huntington disease development has been gaining momentum. I plan to study the effects that different DNA repeat sizes in Huntingtin gene have on the disease progression, through the repeats’ influence on the microglia’s behaviour and function as well as on the neurons’ reaction to synaptic pruning. Further, I will check if correcting either microglia/neurons or both would be useful in reducing the cellular symptoms of Huntington’s. The results will throw light on early development changes (influenced by different sizes of DNA repeats) that would occur in Huntington’s disease and also reveal how they impact a disease like Huntington’s, which usually affects patients late in their life.

In human cells, DNA is folded such that distant points on the linear genome may lie close together in 3D space. This allows interactions between some regions of DNA while separating others, thus dictating the connections between genes and regulatory elements, and exerting control over gene activity. When 3D genome organization is disrupted, the wiring of genes and regulatory elements can be altered and lead to aberrant interactions that inappropriately activate pro-cancer programs.

Viral infections cause 10% of cancers, of which 50% are attributable to human papillomaviruses (HPV). Cervical cancer is an HPV-driven disease, and in over 80% of cases, viral DNA becomes inserted (“integrated”) into the DNA of infected cells, leading to genome disruption. I will profile DNA folding in cervical cancer cells to investigate how HPV integration disrupts the organization and regulation of the host genome, and how this dysregulation contributes to cancer.

My study will contribute to understanding the role of HPV integration in cervical cancer. Findings in this context may improve our understanding of genome dysregulation in other HPV-associated cancers, and provide general insights into how viral integration can promote cancer progression.

This project aims to understand the basic function of the skeletal muscle, and how mistakes in this function can lead to life-threatening disease. A key element of the complex biochemical process known as muscle contraction is a specific particle, named calcium ion. Both the heart and skeletal muscle tissues rely on the movement of calcium ions within each individual muscle cell. This movement occurs through specialized proteins that form ‘pathways’ or ‘channels’. When this pathway doesn’t work properly, however, there can be deadly consequences. In the heart, for example, mutations in the DNA can lead to faulty channel proteins that can no longer allow the normal passage of the calcium ions. This leads to heart rhythm disorders that can result in sudden cardiac death. How exactly the mutations cause this is not fully understood. We aim to understand this, by looking at the detailed 3-dimensional structure of the pathway, and by comparing healthy proteins with diseased versions. Because proteins are too small to see with the naked eye or even with very good light microscopes, we need to use a special tool. We will make use of a so-called ‘electron microscope’, whereby the protein is bombarded with electrons instead of light.

The makeup of bacterial communities in the gut is strongly linked with inflammatory bowel disease (IBD) including Crohn’s disease and ulcerative colitis. Pathobionts like E. coli are opportunistic pathogens that exacerbate gut inflammation in IBD but respond poorly to antibiotics. Bacteriophages (phages) – highly specific bacterial viruses – can alter gut microbiome composition, and so could be used in IBD treatments. Phages, however, undergo evolution – they change over time in response to their environment. Their safe and effective use in treatments therefore requires an understanding of how they co-evolve with the pathobionts in the gut. Here, I will study E. coli pathobiont and phage co-evolution in the gut in response to malabsorption – a key symptom of IBD that causes high gut osmolality (concentration of molecules). Bacteria can adapt to these changes by regulating osmotic channels, but at a cost: phages use those channels to infect. By combining a computational model of bacteria-phage growth with evolution experiments performed in the gut, I will determine the role played by malabsorption in driving bacteria-phage co-evolution and reducing pathobiont load, in turn informing the development of phage therapies for IBD.

Obesity and type 2 diabetes are significant public health issues, with 31% of British Colombians living with prediabetes or diabetes. Not participating in regular physical activity increases the risk for obesity and type 2 diabetes but we still don’t know exactly how. Within days of switching from high activity to inactivity, people have an increase in the blood sugar lowering hormone insulin but at the same time become resistant to insulin’s action. This is followed by weight gain.

Recent research has found that high insulin levels can cause insulin resistance and weight gain. It is possible, then, that the increased insulin level seen when becoming physically inactive causes insulin resistance and weight gain, increasing the risk of obesity and type 2 diabetes. Our study will test this hypothesis directly by using genetically modified mice that make less insulin. These mice will perform high physical activity on running wheels and then transition to low physical activity when the wheel is locked.

By having a greater understanding on the mechanisms behind physical inactivity increasing the risk of obesity and type 2 diabetes, our findings could help develop treatments to prevent the onset of these diseases.

Organ transplantation is a lifesaving therapy. In 2021, in Canada around 2,782 organ transplants were performed. Key to success in organ transplantation is to suppress the immune system and prevent rejection. Current treatment using immunosuppressive drugs have reduced the incidents of rejection, however, such global immunosuppression leads to severe side effects. Thus, new approaches are needed for improved graft survival. Graft rejection is a comprehensive immune reaction initiated due to the damage of blood vessel lining (glycocalyx) during organ procurement and preservation. Such damage mediates the migration of a variety of immune cells post-transplantation, and worsen overtime triggering rejection. In this project, we will rebuild native immune-deactivating activity using immunosuppressive polymer conjugates via a novel organ engineering approach to prevent such damage and graft rejection. We will study the mechanism of this approach and apply it in the transplantation of arteries and kidneys as proof-of-concept. This new organ engineering will reduce the post-transplantation treatment costs, improve patients’ quality of life and may lead to transplantation without immunosuppressive drugs.