Ronald Kahn, M.D. (Joslin Diabetes Center, Medicine) has been investigating the mechanism of insulin action and its alterations in insulin resistant states, including type 2 diabetes, obesity and metabolic syndrome for over 35 years. He covers four major areas of research: 1) The largest activity is devoted to understanding insulin action and insulin resistance. In this area, his group has projects focusing on the insulin receptor itself, the insulin receptor substrate proteins and the PI 3-kinase pathway, which is central to insulin’s metabolic actions. 2) Adipose tissue development and function and how it affects insulin sensitivity and risk of metabolic disease. This includes studies of brown vs. white fat, but also focuses on the heterogeneity of white adipose tissue. 3) Environmental modifiers of insulin sensitivity, especially the role of diet and the gut microbiome. The Kahn lab has also recently integrated metabolomics as a potential mediator of the microbiome effects. 4) The role of insulin signaling in aging and age related diseases, including neurodegeneration. This includes studies of insulin action on neurons and astrocytes, but also the role of the mitochondrial sirtuins on metabolism in health and disease.