Research in the Kahn laboratory focuses in four related and highly integrated areas, which are central to both type 1 and type 2 diabetes:  1) mechanisms of insulin and IGF-1 signaling in control of metabolism; 2) how insulin signaling is altered in diabetes, obesity and insulin resistant states; 3) heterogeneity of adipose tissue and how different adipose depots affect metabolism; and 4) the impact of genes, aging and the environment on these processes.

Since our discovery that the insulin receptor is an insulin-stimulated receptor tyrosine kinase, the Kahn lab has focused on understanding how this event activates the complex signaling network that leads to the multiple actions of insulin. We showed that following activation of the receptor kinase, several insulin receptor substrates (IRS proteins) become tyrosine phosphorylated and serve as intracellular messengers by docking to other intracellular signaling proteins that link insulin to two major intracellular cascades - one mediated by the enzyme phosphatidylinositol 3-kinase (PI 3-kinase) and the other mediated by the Ras-MAP kinase pathway. These form the critical nodes in the insulin signaling network and are points of regulation in type 1 and 2 diabetes.

Using a wide range of genetic and biochemical approaches, including creation of genetically engineered mice and human iPS cells lines, the Kahn laboratory is working to define the specific pathways that lead to each of insulin’s actions and how they are modified in diabetes and other insulin resistant states. Through these approaches, we have defined the role of insulin in both classical target tissues for insulin action (liver, muscle and fat) and non-classical targets such as the brain, endothelial cell and β-cell. We also study mechanisms of insulin resistance and its impact on function of these tissues. These studies are being used as a platform for developing new therapeutics, including new types of insulins, as well as insulin sensitizers, which are critical for future treatments for type 1 and type 2 diabetic patients.  

Recently, we have shown how loss of insulin action in the brain in diabetes can affect brain cholesterol metabolism and brain function. These findings are critical for understanding the reason for the increased risk for neurodegenerative complications, which affect both type 1 and type 2 diabetic patients. To identify how genetic and environmental alterations might contribute to the development of diabetes in humans and rodents, we have assessed the effects of the gut microbiome in different strains of mice on development of obesity, insulin resistance and diabetes. 
 
The biology of adipocytes and their special role in metabolism and insulin resistance is another major area of interest.  We have shown how various depots can affect metabolism and what determines fat distribution and the nature of adipocyte lineages, including the formation of brown vs. white fat and subcutaneous vs. intra-abdominal fat. We have found important roles for a variety of fundamental developmental genes, and are exploring these through the creation of knockout and knockdown mouse and cellular models. Recently, we have also studied the role of microRNAs as regulators of adipose biology and metabolism.

Finally, we are also interested in the problem of aging and the relationship between insulin action, obesity and lifespan. Again we have taken advantage of some of our genetic models to define better the physiological connections between these events. We are now studying the insulin signaling pathway may from a connection between aging and metabolism at the molecular level. In this area, we also have been studying the role of sirtuins, especially Sirt3 and Sirt5, and the role of miRNAs in adipose tissue in aging and metabolic control. This area is important for patients with type 1 and type 2 diabetes, as many are living longer with their disease, and age is a major risk factor for development of disease complications.  

Medical School: University of Louisville
Honorary Degrees:

• Master of Science from Harvard University
• Doctor of Science from University of Paris, University of Louisville, University of Geneva and Washington University in St. Louis
• Honorary Doctor of Medicine from University of Copenhagen
• Honorary Professor and Director of the Diabetes Center at Peking University School of Medicine

Dr. Kahn has published over 800 papers and is among the most highly cited scientists in the field and in diabetes worldwide.

Dr. Kahn’s other notable accomplishments include:

• Recipient of The Harold Hamm International Prize for Biomedical Research in Diabetes by The Harold Hamm Diabetes Center in 2015
• Recipient of the Manpei Suzuki International Prize for Top Diabetes Researcher Worldwide in 2009
• Recipient of the Basic Science Award of the International Diabetes Federation in 2015
• Recipient of the Frontiers in Science Award, American Association of Clinical Endocrinologists in 2010
• Recipient of the  Distinguished Leader in Insulin Resistance, World Congress of Insulin Resistance in Diabetes and Cardiovascular Disease in 2010
• Recipient of the inaugural Helmholtz Diabetes Lecture Award by the Helmholtz Diabetes Center in 2013
• Recipient of the 2015 Endocrine Regulation Prize by Le Fondation IPSEN in 2015