Internal Medicine, Bone & Mineral Diseases
Campus Box 8301
660 S. Euclid Ave.
St. Louis, MO 63110
Phone (314) 362-2869
Metabolic Regulation and Obesity
Signal Transduction/Hormone Action
Category(ies) of Research:
Descriptor of Research:
Diabetes has rapidly become an epidemic health concern, and unfortunately outpaced the development of a cure or improved treatment options. Drug discovery has focused heavily on target molecules in the cells they are trying to fix. Our research approaches therapeutic intervention for diabetes and obesity in a novel manner by targeting the environment surrounding diseased cells. Cells exist in a matrix of molecules that organizes the cells into a functional tissue. These proteins provide mechanical support to tissues, and control key cellular processes by regulating the biological signals that cells receive. Consequently, disturbances in the ECM translate into cellular dysfunction. Our research demonstrates that ECM components have direct and dramatic consequences on metabolic disease and should therefore be considered a site of pharmacologic intervention. Specifically, we are interested in the mechanisms by which ECM microfibrils influence energy storage and utilization through interaction with growth factors. Previous findings have demonstrated that deletion of the ECM protein MAGP1 results in impaired thermogenesis followed by metabolic disease, and MAGP1 regulates signaling pathways involved in mitochondrial function. Our efforts are now focused on determining the precise molecular mechanism by which MAGP1 functions in energy metabolism, and testing recombinant MAGP1 for the capacity to increase energy expenditure in adipose tissue. Our goal is to expand knowledge of growth factor regulation by microfibrils and the relevance of these interactions to energy utilization and mitochondria function.