Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine at HMS, and professor of medicine at Brigham and Women’s Hospital, is a co-recipient of the 2015 Albert Lasker Basic Medical Research Award. He shares the award with Evelyn Witkin of Rutgers University.
Elledge and Witkin were honored for discoveries that have illuminated the DNA damage response, a cellular pathway that senses when DNA is altered and sets in motion a series of responses to protect the cell. This pathway is critical to a better understanding of many diseases and conditions, such as cancer.
The award, widely considered to be among the most respected in biomedicine, was presented to the two researchers on September 18 in New York City.
“Steve is an amazing scientist, mentor, and colleague,” said Jeffrey S. Flier, HMS dean. “His insights into the basic mechanisms of the DNA damage response have profoundly enriched our understanding not only of the fundamental genetics of all cellular life, but also of how we conceptualize many diseases and conditions.”
Added Elizabeth Nabel, president of Brigham and Women’s Health Care, “Steve is courageous and insatiably inquisitive. As a devoted mentor, he is deeply committed to guiding the careers of young investigators.”
Elledge often describes the process by which a cell duplicates itself as akin to the duplication of a small city. It is a vastly complex process that requires many levels of intricate coordination. Each cell contains a detailed blueprint for this entire process: DNA.
Yet not every duplication results in a perfect copy. That is because each time a cell makes a copy of itself, DNA is vulnerable to damage, not only from faulty cellular processes, but also from such things as environmental chemicals. As DNA damage accumulates, it profoundly complicates a cell’s ability to make a faithful copy of itself. This can lead to serious illnesses, birth defects, cancer, and other health problems.
While Witkin discovered how bacteria respond to DNA damage, detailing the response to UV radiation, Elledge uncovered a DNA-damage-response pathway that operates in more complex organisms, including humans.
Over the years, Elledge and his colleagues elucidated a signaling network that informs a cell when DNA sustains an injury.
Called the DNA damage response, this network senses the problem and sends a signal to the rest of the cell so it can repair damaged areas. The pathway thus helps keep the genome stable and suppresses adverse events such as tumor development.
When individuals are born with mutations in this pathway, they often have severe developmental defects. If the pathway is interfered with later in life, cancer can result.
Photo: Emmanuel Ording