Dean's Distinguished Lecture Series

Nobel Prize in Chemistry 2012
Prize motivation: For Studies of G-Protein-Coupled Receptors

NOBEL CITATION
Communication between the cells in your body are managed by substances called hormones. Each cell has a small receiver known as a receptor, which is able to receive hormones. In order to track these receptors, in 1968 Robert Lefkowitz attached a radioactive isotope of iodine to the hormone adrenaline. By tracking the radiation emitted by the isotope, he succeeded in finding a receptor for adrenaline and studied how it functions. It was later discovered that there is an entire family of receptors that look and act in similar ways - "G-protein-coupled receptors". Approximately half of all medications used today make use of this kind of receptor.

Robert J. Lefkowitz was born in 1943 and raised in New York, Bronx, in a family with Polish heritage. Robert Lefkowitz is married and has five children.

Robert J. Lefkowitz, MD studied chemistry and trained to become a MD at Columbia University. In 1968, he began his research career at the NIH as a clinical associate. In the summer of 1972, he was recruited by Duke University Medical Center to join their faculty to develop a program in “molecular cardiology.” This was to begin upon the completion of his fellowship at Massachusetts General Hospital (MGH) in 1973. He initially declined their offer but, when they subsequently raised the ante including an Associate Professor rank in Medicine, it seemed like an offer “He couldn’t refuse.”

Robert J. Lefkowitz, M.D. is James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at the Duke University Medical Center. He has been an Investigator of the Howard Hughes Medical Institute since 1976. Dr. Lefkowitz began his research career in the late 1960’s and early 1970’s when there was not a clear consensus that specific receptors for drugs and hormones even existed.

His group spent 15 difficult years developing techniques for labeling the receptors with radioactive drugs and then purifying the four different receptors that were known and thought to exist for adrenaline, so called adrenergic receptors. They perfected variety of tools such as photoaffinity probes and affinity chromatography matrices for the various adrenergic receptor subtypes as well as computer based analytical approaches for analyzing ligand binding data. These approaches greatly facilitated the discovery of new receptor subtypes and led to new ways of conceptualizing receptor G protein interactions (for example the ternary complex model). Dr. Lefkowitz transformed the understanding of what had become known as G protein coupled receptors because of the way the receptor signal for the inside of a cell through G proteins, when he and his colleagues cloned the gene for the beta2-adrenergic receptor.

Along the way to receipt of the Nobel Prize he received a number of other awards for his research. Among others, these include: The Gairdner Foundation International Award (1988); Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular Research (1992); Fred Conrad Koch Award – The Endocrine Society (2001); Jessie Stevenson Kovalenko Medal of the USA National Academy of Sciences (2001); Institut de France – Fondation Lefoulon-Delalande Grand Prix for Science (2003); The National Medal of Science (2007); The Shaw Prize in Life Science and Medicine (2007); The Albany Medical Center Prize in Medicine and Biomedical Research (2007); Research Achievement Award, American Heart Association (2009); BBVA Foundation Frontiers of Knowledge Award (2010).

He has been elected to membership in the National Academy of Sciences, the Institute of Medicine of the National Academy of Sciences, the American Academy of Arts and Sciences, The American Society of Clinical Investigation and The Association of American Physicians.