Dr. Kahn is an internationally recognized researcher, a Senior Investigator and Head of the Section on Integrative Physiology and Metabolism, the Mary K. Iacocca Professor of Medicine at Harvard Medical School and Vice Chairman of the Joslin Board. Educated at University of Louisville, he trained at Washington University and served as the Section Head of Cellular and Molecular Physiology of the Diabetes Branch of NIH. In 1981, he became Research Director of Joslin, and in 1984, Professor of Medicine at Harvard. In 1986 he was awarded the Iacocca Professorship. From 2000 to 2007 Dr. Kahn served as Joslin President and Director.

Dr. Kahn has received the highest scientific awards of the American Diabetes Association, U.S. Endocrine Society, British Diabetes and Endocrine Societies, Juvenile Diabetes Research Foundation, International Diabetes Federation and American Federation for Clinical Research, as well as many other honors, including election to the National Academy of Sciences and the Institute of Medicine. He chaired the congressionally established Diabetes Research Working Group and holds honorary doctorates from the Universities of Paris, Louisville and Geneva and an honorary professorship from Peking University.

Discoveries in Insulin Signaling
Over three decades, C. Ronald Kahn, M.D., and colleagues have literally defined the field of insulin signal transduction and mechanisms of altered signaling in disease. His laboratory discovered the insulin receptor tyrosine kinase, identified its first two major substrates and showed how these were linked in other intracellular molecules, especially phosphatidylinositol (PI) 3-kinase, to create a complex signaling network through which insulin exerts multiple effects on metabolism and growth. His laboratory demonstrated how this network is altered in insulin-resistant states, such as type 2 diabetes and obesity, and the impact of genetics and environment on these signaling functions.

In an elegant series of studies using genetically engineered mice, Kahn’s laboratory defined the role of the insulin receptor and various downstream molecules in insulin action and insulin resistance. This work includes creation and characterization of single-gene knockouts, compound knockouts (which mimic the polygenic nature of diabetes), multiple tissue-specific knockouts and the use of RNA interference in both cells and intact animals. These studies demonstrate the specific roles of each tissue in control of glucose and lipid metabolism and illustrate how the various signal molecules act to produce a complex integrated network where different substrates and molecules serve unique, complementary roles. Kahn’s laboratory showed that insulin receptors in tissues such as the brain, beta cells and endothelial cells also play important roles in normal and disease states, including obesity, hyperlipidemia, gallstone formation and Alzheimer’s disease.

Exploring Fat Cell Biology
Additionally, Kahn’s laboratory defined the roles of insulin and IGF-1 signaling on adipocyte development and function. Using both gene expression and fat transplantation, Kahn’s lab identified differences between white fat in different areas of the body, which may account for why people with abdominal obesity are more prone to developing diabetes than people with peripheral obesity. The fundamental genes controlling developmental patterning may play a role in determining the amount and function of fat in different depots.

Leveraging New Genetic Technologies
Dr. Kahn leads a large consortium of investigators at multiple institutions using gene and protein expression studies to define obesity, diabetes and other insulin-resistant states (the Diabetes Genome Anatomy Project). These studies have defined the role of genes and the environment in the development of type 2 diabetes. Several new pathways in the pathogenesis of type 2 diabetes have been elucidated, including the role of the genes of mitochondrial oxidative phosphorylation, the role of developmental genes in fat distribution and obesity, and the role of the altered gene expression in pancreatic beta cells in islet function. This research also provides insight about new targets for the treatment or prevention of this disease. 

Selected References

Taniguchi CM, Emanuelli B, Kahn CR.  Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7:85-96, 2006.

Gesta S, Bluher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR.   Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci U S A 103:6676-6681, 2006.

Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, O’Connell PJ, Gonzalez FJ, Kahn CR.  Loss of ARNT/HIF1b mediates altered gene expression and pancreatic islet dysfunction in human type 2 diabetes. Cell 122:337-349, 2005.

Blüher M, Kahn BB, Kahn CR.  Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572-574, 2003.