Grant: Foundation Grant

<html> <body> <p>Our <strong>overarching research goal</strong> is to understand what constitutes a healthy &#x03b2; cell and what causes &#x03b2; cells to fail in diabetes mellitus (DM). The proposed <strong>&#x03b2; Cell Health and Diabetes (BCHD)</strong> program will identify causes of &#x03b2; cell failure and devise strategies to preserve or restore &#x03b2; cell function. Ranked in the top 3% of all applications in Stage 1, our proposal integrates and streamlines 3 interrelated CIHR funded projects to leverage shared resources and accelerate knowledge translation (KT).<br> <br> <strong>Objectives:</strong> <br> <strong>1. Discover metabolites that cause &#x03b2; cell failure in DM (MOP-324754)<br> </strong> Circulating metabolites have enormous potential to lead us to the cause of &#x03b2; cell dysfunction in DM. Using global screening platforms, we will identify metabolites associated with the earliest stages of &#x03b2; cell failure. We will then assay these metabolites for their contribution to &#x03b2; cell failure and explore mechanisms underlying this effect. Finally, we will work with our KT partners to explore ways to preserve or restore &#x03b2; cell function by neutralizing the effects of the identified metabolites.<br> <strong> <br> 2. Use novel, sensitive biomarkers to detect or predict DM (MOP-324754)<br> </strong> Early identification of DM risk represents an opportunity to better manage or even prevent DM. Having discovered metabolites linked to DM risk or development in <em>Objective 1</em>, we will develop an assay to detect and quantify a select panel of these metabolites. Such an assay will aid current methods to predict DM, and provide new benchmarks for the evaluation of interventions that prevent or treat DM.<br> <strong> <br> 3. Identify novel targets to preserve or restore &#x03b2; cell function (MOP-102588)</strong> <br> New therapeutics to specifically improve &#x03b2; cell function in DM are&nbsp;greatly needed. We will continue to use innovative methods to discover and mechanistically understand proteins involved in the secretory process and explore ways to enhance &#x03b2; cell function. One strategy will identify novel chemicals and targets that potentiate insulin secretion, and others will use proteins such as the GLP-1 receptor to discover &#x03b2; cell enhancers.<br> <strong> <br> 4. Create functional &#x03b2; cells from stem cells (MOP-111241)<br> </strong> Stem cell-derived &#x03b2; cells will potentially revolutionize therapy for type 1 diabetes, but can only do so if they exhibit tight control of insulin secretion. With our expert network, we are collectively poised to develop fully functional, transplantable &#x03b2; cells. We will accomplish this by carefully characterizing &#x03b2;-like cells produced by our experts, and through the development of innovative differentiation protocols in our lab. Our goal is to produce human &#x03b2;-like cells that exhibit precise nutrient-responsive insulin secretion.<br> <br> <strong>BCHD Core Expertise:</strong> <br> I direct one of the most productive &#x03b2; cell pathobiology programs in Canada. Our <em>expert network</em> comprises an outstanding team of academics, clinicians and industry partners with a proven track record of collaboration. Our strong international ties provide BCHD with access to diverse patient populations and ensure that our work is fully translational.<br> <br> <strong>Training:</strong> <br> The proposed BCHD program extends my existing research program, which has produced over 50 HQP. My mentorship strategy focuses on 1) development of innovative and diverse skills, and 2) enhancing knowledge through a rich training environment to prepare trainees for careers in health-related fields.<br> <br> <strong>Impact:</strong> <br> The BCHD program will advance our understanding of the causes of &#x03b2; cell failure and offer new strategies for detection and treatment of DM.</p> </body> </html>