Metabolic Regulation and Obesity
Signal Transduction/Hormone Action
Islet Biology and Immunology
Category(ies) of Research
Description of Research
My laboratory focuses on the pharmacology and chemical biology of nuclear receptors (NRs). Given the number of NRs that play a role in regulation of metabolic pathway, it is natural that my lab has been drawn to focus a number of projects in the area of diabetes and metabolic disease. I spent a decade working in the private pharmaceutical industry in drug discovery focused on NR targets and I brought this experience with me back to academia where I collaborate heavily with medicinal chemists and structural biologist to develop novel ligands for NRs that may hold utility in the treatment of diabetes/obesity. I will highlight two projects that are operating currently with relevance to diabetes and obesity. We developed the first synthetic ligands targeting REV-ERB that could be used in vivo and discovered that activation of this receptor led to substantially improved metabolic function via increased oxidative function in the skeletal muscle. We continue to examine these compounds as well as to improve their function toward a potential novel treatment for type 2 diabetes. We have developed high affinity agonists targeting the ERRs, which play a very important role in regulation of oxidative metabolism and mitochondrial biogenesis. We have demonstrated that treatment of obese mice with these compounds improves metabolic function considerably. Beyond these two projects, we also have a significant focus on the role of the immune system in metabolic disease and are evaluating methods to pharmacological target the immune system to improve metabolic function.