Research Pillar: Biomedical Research

When we walk, our bodies take each step slightly differently. This variability is how the brain explores movements so we can adapt to changing environments (e.g. bump in the sidewalk) or new challenges (e.g. painful motion). Pain from injuries or disease can lower this natural exploration because our brain avoids painful movements, ultimately limiting our ability to adapt. My study aims to understand how pain affects this variability-adaptation process in walking. In these studies, we will use electrical stimulation to create artificial knee pain, since naturally occurring pain fluctuates and is difficult to control. By synchronizing the painful stimulation with walking motions, we can precisely control the timing and severity of pain so we can measure the variability-adaptation process in real-time. First, we will test how knee pain changes movement variability. Then, we will measure how adaptation is affected by lower variability created by the pain. To conduct these projects, we will develop new wearable technology that combines electrical stimulation and motion tracking devices to perform this work in places outside the lab. The results will inform how movement variability can affect rehabilitation of painful conditions.

During the development of Type 2 diabetes, the body often makes more of the blood sugar-lowering hormone insulin than normal. Recent research suggests excess insulin may cause weight gain and insensitivity to insulin. Studies from our lab showed that preventing this increase of insulin can reduce weight gain and extends lifespan in mice. Too much sugar consumption also contributes to obesity and diabetes, but how this happens is still unclear. Therefore, we aim to find out whether reducing insulin can prevent the detrimental effects of high sucrose and identify the underlying causes of obesity and diabetes. So far, our experiments with mice who were given sucrose drink in place of water, have revealed that mice given that have been genetically modified to produce less insulin are protected from higher body weight and blood sugar levels. With funding from Health Research BC, we will analyze the liver, muscle, and fat of these mice using powerful techniques that can profile thousands of genes and proteins in these tissues, rather than just a few at a time. These analyses will reveal the detailed changes in the cells in response to sucrose and insulin, which will tell us how they cause obesity and diabetes and help us develop strategies for preventing diabetes.

The cultivation of stem cells to insulin-producing beta cells offers an unlimited source of transplantable material for diabetes treatment. However, currently manufactured beta cells do not function precisely like the healthy ones in our bodies. Human islets are cell clusters mainly comprised of a mix of endocrine cell types, and interactions among them are critical in controlling insulin secretion. However, this point has been overlooked by current manufacturing methods that typically attempt to make clusters enriched only for beta cells. The absence of other islet cell types may therefore be a leading cause of the failure to obtain properly regulated insulin production. We recently developed a method to coax stem cells into islet clusters that are enriched for major endocrine cell types. Interestingly, these islets formed through an essential but unidentified “budding process” and self-organized into distinct cellular arrangements over time. Our goal is to elucidate the mechanisms that regulate islet formation, including the ways in which the cells assemble and impact islet function. Success could facilitate methods to manufacture islet cells with more robust insulin production and guide cell replacement strategies for diabetes.