In addition to its role in regulating weight, leptin is also involved in regulating many of the physiological responses that are seen with changes in nutritional state. Studies in Dr. Friedman’s lab seek to elucidate the mechanism by which a single molecule, leptin, can modulate a complex behavior, feeding, and how leptin and other mechanisms control body weight and the pathogenesis of obesity. Dr. Friedman is also part of a collaboration to establish the genetic basis of human obesity on the Pacifi c island of Kosrae.

In December 1994, Dr. Friedman and his colleagues identifi ed a gene in mice and humans called obese (ob) that codes for a hormone he later named leptin, after the Greek word leptos, for thin. Mice that lack ob, and thus do not produce leptin, are massively obese, weighing as much as three times more than their normal littermates. Dr. Friedman showed that after normal and ob mice are injected with synthetic leptin, they are more active and lose weight. In addition, humans lacking leptin eat copious amounts and are massively obese, and leptin treatment of these individuals leads to massive weight loss. The dramatic effect of leptin in these patients establishes a key role for this hormone in human physiology.

However, the majority of obese people have very high levels of leptin circulating in their blood. Dr. Friedman’s lab went on to show that high leptin levels are associated with resistance to leptin and provided evidence that suggests that animals destined to be obese increase their production of leptin to satisfy a higher set point for weight. These observations have reframed views on the pathogenesis of obesity and suggested that the development of approaches to improve leptin response in resistant individuals could provide new treatments for obesity. In order to identify the molecular basis of leptin resistance, Dr. Friedman is also studying the neural circuit that is activated by leptin.

Leptin itself has proven to be an effective therapy for a number of other human conditions associated with low leptin levels, including several different forms of human diabetes and a condition known as hypothalamic amennorhea. This condition, which develops in extremely thin women — often ballet dancers or longdistance runners — is one of the most common causes of infertility in women, and leptin treatment has been shown to restore reproductive function in these patients. In addition, a subset of obese individuals also has relatively low leptin levels, and it appears that these individuals lose weight with leptin treatment. Dr. Friedman is now performing clinical studies at The Rockefeller University Hospital to determine the effects of leptin on the changes that occur in the body during signifi cant weight loss achieved by obese patients on a very low-calorie diet.

Dr. Friedman, with Jan Breslow and Markus Stoffel, also leads a team of Rockefeller researchers that is studying the genetic causes of a cluster of health problems called Syndrome X — obesity, diabetes, high blood pressure and high blood cholesterol — in a remote population of over 3,000 people on the Micronesian island Kosrae. By analyzing the genetic inheritance patterns of the entire Kosraean population, Dr. Friedman and his colleagues hope to solve the ongoing mystery of why some people develop these diseases while others with the same lifestyle do not.

CAREER

Dr. Friedman graduated from Rensselaer Polytechnic Institute magna cum laude 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. In 1991 he was named head of laboratory, and in 1995 he was promoted to professor. He was appointed the Marilyn M. Simpson Professor in 1999. He has been an investigator at the Howard Hughes Medical Institute since 1986. Dr. Friedman also directs the Starr Center for Human Genetics, one of the country’s largest centers for the study of diseases linked to heredity.

A member of the National Academy of Sciences and its Institute of Medicine, Dr. Friedman’s most recent honors include the 2007 Jessie Stevenson Kovalenko Medal, the sixth Danone International Prize for Nutrition, the 2004 Gairdner Foundation International Award and the 2004 Passano Foundation Award.