Heads of Laboratories
Jeffrey M. Friedman, M.D., Ph.D.
Investigator, Howard Hughes Medical Institute
Marilyn M. Simpson Professor
Laboratory of Molecular Genetics
Leptin is a hormone secreted by adipose (fat) tissue in proportion to its mass that in turn modulates food intake relative to energy expenditure. Increased fat mass increases leptin levels, which in turn reduces body weight; decreased fat mass leads to a decrease in leptin levels and an increase in body weight. By this mechanism, weight is maintained within a relatively narrow range. Defects in the leptin gene are associated with severe obesity in animals and in humans.
The recent identification of the hypothalamic cells that express the leptin receptor is enabling Dr. Friedman and his colleagues to delineate the precise neuronal effects of leptin and the mechanisms by which this single molecule can alter a complex behavior. Recent studies have revealed that leptin reduces food intake by decreasing the pleasure associated with food. Dr. Friedman’s lab has identified a specific neural population in the hypothalamus that expresses a bioactive peptide known as MCH, which plays a key role in sensing the reward value of food. His ongoing studies seek to understand how leptin modulates the activity of these neurons as well as to identify additional neural populations that regulate feeding.
The Friedman lab is also using transgenic mice to identify DNA regulatory elements that change expression of a reporter gene controlled by the leptin gene proportionately with changes in adipose tissue mass. They have modified a series of leptin bacterial artificial chromosome clones so that the leptin DNA regulatory elements direct the expression of luciferase, enabling them to identify DNA regulatory sequences that control leptin gene expression. The goal of these studies is to identify a novel lipid sensing signaling pathway in adipocytes and possibly other cell types.
Leptin has potent metabolic effects to improve insulin action and reduce the lipid content of peripheral tissues as retained and is now an FDA-approved drug for the treatment of severe lipodystrophy, a form of diabetes. The Friedman lab is studying the mechanism responsible for leptin’s antidiabetic function; current data suggest that leptin interferes with both the production and action of glucagon, a hormone that acts to increase blood glucose by opposing the effects of insulin.
In collaboration with Tayfun Ozcelik at Bilkent University in Ankara, Turkey, the Friedman lab is conducting studies of consanguineous families that include patients who are either morbidly obese, extremely lean, or have polycystic ovary disease (PCOS), which is associated with resistance to insulin. The team expects that analyses of the DNA sequences from these populations will reveal DNA mutations that contribute to differences in weight or that lead to PCOS.
Dr. Friedman graduated from Rensselaer Polytechnic Institute and, in 1977 at the age of 22, received his M.D. from Albany Medical College of Union University. After completing two residencies at Albany Medical Center Hospital, Dr. Friedman came to Rockefeller as a postgraduate fellow and associate physician in 1980. In 1986 he received his Ph.D., working in the lab of James E. Darnell Jr., and was appointed assistant professor. He was named head of laboratory in 1991, professor and in 1995 and Marilyn M. Simpson Professor in 1999. He has been an investigator at the Howard Hughes Medical Institute since 1986.
A member of the National Academy of Sciences and its Institute of Medicine, his honors include the King Faisal International Prize in Medicine, the BBVA Frontiers of Knowledge Award in Biomedicine, the Fondation IPSEN Endocrine Regulation Prize, the Albert Lasker Award for Basic Medical Research, the Shaw Prize in Life Science and Medicine, the Keio Medical Science Prize, the Jessie Stevenson Kovalenko Medal, the Danone International Prize for Nutrition, the Gairdner Foundation International Award and the Passano Foundation Award.
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