Grant: Foundation Grant

<html> <body> <p> <b>Program Direction and Major Research Objectives</b> <br>Diabetes is a debilitating disease of dysregulated glucose homeostasis due to insufficient production of insulin from pancreatic beta-cells, affecting &gt;9 million Canadians. Insulin therapy has several drawbacks including challenges of dosing in type 1 diabetes and insulin resistance in type 2 diabetes. A large network of hormones regulates glucose homeostasis, with great potential for non-insulin based diabetes therapies. The overall goal of my research program is therefore to better define the hormonal pathways that regulate glucose metabolism with a view to developing novel strategies to treat diabetes. Using several complementary tools and animal models, we seek to determine how the hormones leptin and FGF21 potently lower blood glucose levels, even in the setting of severe diabetes. Our objectives are to understand what tissues mediate the effects of these hormones, and what mechanisms are involved. We also plan to search for new glucoregulatory hormones by unbiased proteomics analyses of human plasma samples. Given that an adverse nutritional environment during development can lead to dysregulated production of glucoregulatory hormones, we will examine the effects of specific nutritional alterations on beta-cell development and hormonal control of glucose homeostasis in a novel mouse model. This work might reveal strategies to prevent diabetes through dietary recommendations or hormone-targeted pharmacological interventions. We will also transplant mice with human embryonic stem cell derived pancreatic precursors to model human pancreas development with exposure to different diets, drugs, and hormones. This work has tremendous clinical relevance given that human trials of pancreatic precursors for type 1 diabetes have begun. Ultimately, we hope our research program will contribute to improved health outcomes in patients and reduced burden on health care systems.<br> </p> <p> <b>Core Expertise</b> <br>My lab has the capacity to address questions from molecular to cellular to whole organism, using model cell lines, differentiated stem cells, zebrafish and genetically engineered rodents. We utilize tissue-specific knockdown or reintroduction of genes, cell transplant and surgical manipulations to address the role of hormone actions in a site-specific manner. We assess the effects of environment on metabolic function with dietary manipulations, from neonates to adults. We have advanced equipment for high-throughput analyses of cellular function and pathways, for whole animal imaging, and for metabolic phenotyping. I have strong networks of collaborators including basic scientists, clinicians and industry leaders. I have assembled and led multidisciplinary teams and effectively engaged researchers across Canada and around the world to bolster our research enterprise. I actively collaborate with industry, including large pharmaceutical companies, as we strive to translate our findings to the clinical setting.<br> </p> <p> <b>Mentoring and Training Activities</b> <br>I am committed to providing trainees with valuable experience in cutting edge diabetes research in an outstanding environment. My research program will continue to provide significant opportunities for trainees to learn a broad array of sophisticated techniques in multiple model systems. Trainees will also gain valuable skills in mentoring, teaching and communication, to ensure they reach their full potential and are competitive as they prepare for the next stage of their career.</p> </body> </html>