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Elledge, Harvard professor, wins annual Rosenstiel Award

Published: November 2, 2012
Section: Features

Harvard Professor and research scientist Dr. Stephen Elledge won this year’s Rosenstiel Award for Distinguished Work in Basic Medical Science, founded by Brandeis and established in 1971. The $30,000 award honors scientists who discover mechanisms underlying disease and development.

“It is centered on … understanding the underlying cellular and molecular processes that allow cells and organisms to function,” Professor James Haber (BIO), the head of the selection committee for the Rosenstiel Award, said. “It has been given to scientists uncovering the basis of sensory perception, the regulation of gene expression, the basis of innate immunity and so on.”

The winner is selected by a panel of about a dozen scientists from the Boston area. Elledge stated his research involves addressing issues such as, “How does the cell know when its chromosomes are damaged? How does it sense the different types of structural alterations in the DNA of chromosomes, and once the existence of this problem is detected, what does it do about it? How does it communicate this problem to the rest of the cell to help ameliorate it?”

According to Haber, “Each year, the Rosenstiel Award committee solicits and receives nominations from scientists all over the world, and then meets to winnow down the nominations to one or more recipients.”

Upon being notified that he was to receive the award, Elledge described his reaction as “very pleasantly surprised, as the past winners are a tremendously talented group of scientists and [I] am proud to be considered to be among them.”

Humble in his achievement, Elledge moved quickly to congratulate his graduate students and postdocs, “whose incredible talent and hard work was responsible for the discoveries we made over the last two years.” He plans to donate some of the money received from the award to his high school, “in order to promote their chemistry program.”

The award is quite prestigious—according to Haber, the selection committee is known for it’s “remarkable record of identifying people before they have been awarded the most prestigious prizes such as the Lasker Prize or the Nobel Prize.”

About one third of the recipients of the Rosenstiel Award have gone on to win the Nobel Prize, including names such as Andrew Fire, Craig Mello, Martin Chalfie, Roger Tsien, Carol Greider, Elizabeth Blackburn, Thomas Steitz, Jules Hoffman, Shinya Yamanaka and Sir John Gordon. Haber states that the selections of the Rosenstiel Award “greatly influence the awarding of these other prizes.”
Strangely enough, Elledge came across the hypothesis of his research as a “complete accident.” While attempting to find a different protein in yeast, the eukaryotic version of the bacterial protein recA, he found a different protein, ribonucleotide reductase. Realizing that this protein, which he found using antibodies to recA, was “completely unrelated” to the protein he was searching for, his experiment had failed.

After some data mining, however, Elledge found that “this protein’s levels were highly induced in response to DNA damage,” leading him to believe in a signal transduction pathway that “senses DNA damage and transmits a signal to activate this protein.” This thought led him to research the protein he had found, believing that there was something important to discover.

Upon following this train of thought, Elledge found that “when damage to a chromosome occurs, a protein kinase cascade is activated that makes a lot of changes in the cell to promote DNA repair and survival.”

This discovery is made extremely important by the way many human diseases function—according to Elledge, in a large number of human diseases such as ataxia telangiectasia, Seckel Syndrome, Fanconi anemia and several types of cancer, most notably familial breast cancer, the “DNA damage response is defective.”

DNA damage response senses damaged cells and kills them by apoptosis or causing them to permanently exit the cell cycle by means of a process called senescence. Many chemotherapies trigger the DNA damage response. Other cancers, caused by “partial defects in the DNA damage response can be killed by further inactivating the response in those tumors.”

Hence, Elledge’s discovery could eventually be used as a “therapeutic target for cancer under certain circumstances.”