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Lasker Winner Darnell To Give Director's Lecture

On Nov. 19 at 3 p.m. in Masur Auditorium, Bldg. 10, the NIH Director's Lecture will feature Dr. James E. Darnell, Jr., winner of the 2002 Lasker Award and the 2002 National Medal of Science. He will speak on blockade of overactive STAT3 as a possible means of defeating cancer.

Darnell has been the Vincent Astor professor and head of the molecular cell biology laboratory at the Rockefeller University since 1974. He is a long-time grantee of NIAID and NCI, and has also received funding from NIGMS and NIDDK. The work described in this lecture, titled "The STAT3 Transcription Factor as a Cancer Target," presents the latest findings from a career marked by breakthroughs in the field of genetic biology.

Dr. James E. Darnell, Jr.
It was Darnell's pioneering studies of RNA processing and his findings on the origin of messenger RNA that provided the foundation for Phillip A. Sharp and Richard J. Roberts' work on RNA splicing. Sharp and Roberts won the Nobel Prize for identifying the way nuclear RNA is cut and selected pieces rejoined to make messenger RNA (mRNA); mRNA is the primary molecule that brings about cell differentiation and development. He subsequently identified signal transducers and activators of transcription (STATs) as proteins within cells that activate specific genes in response to external cytokine stimulation, thus regulating mRNA production. His work on mRNA processing and STATs won him the Lasker Award for Special Achievement in Medical Research.

Born in Columbus, Miss., Darnell is a graduate of the University of Mississippi and Washington University School of Medicine in St. Louis. Over the past four decades, he has held research appointments at NIH, the Institut Pasteur in Paris, the Massachusetts Institute of Technology, Albert Einstein College of Medicine, Columbia University and Rockefeller University.

He began his pioneering work in molecular genetics as a medical student, and in Dr. Harry Eagle's group in the Laboratory of Cell Biology at NIH. At that time, little was known about genetic change as a factor in animal development. In 1962, during his tenure at MIT, he presented the first evidence for RNA processing in the manufacture of ribosomal RNA and the beginning evidence that mRNA also derives from RNA processing. In the early 1990s, his group identified the STATs as latent cytoplasmic molecules activated by cytokines, which then initiated gene activation in the cell nucleus.

Darnell's current work on STAT3 stems from the finding that this particular STAT is persistently active in a large percentage of human cancers, and it functions to prevent apoptosis — the normal programmed cell death pathway that cancer cells avoid. Introducing dominant inhibitors of STAT3 into several different types of cultured human cancer cells, Darnell says, results in the restoration of apoptosis to these immortal cells. Drugs that target and inhibit STAT3 transcriptional ability, he says, "should be excellent anti-cancer drugs," stripping cancer cells of their immortality and returning them to their normal response to cell-death signals.

Darnell has been a member of the National Academy of Sciences and the American Academy of Arts and Sciences since 1973 and has received a number of other awards. In addition to the Lasker and the National Medal of Science, his honors include the American Society for Cell Biology's E.B. Wilson Medal. He has also been honored for fostering the careers of more than 125 young scientists, many of whom have gone on to make important contributions of their own. His books include the definitive works General Virology and Molecular Cell Biology, now in its 5th edition.

Darnell's talk is part of the NIH Director's Wednesday Afternoon Lecture Series. For more information and reasonable accommodation, contact Hilda Madine, 594-5595.

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