Stephen J. Elledge, PhD, the Gregor Mendel Professor of Genetics at Brigham and Women’s Hospital and Harvard Medical School, is a co-recipient of the 2015 Albert Lasker Basic Medical Research Award, widely considered to be among the most respected awards in biomedicine.
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. But 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 even from such entities 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. Witkin discovered how bacteria respond to DNA damage, detailing the response to UV radiation. Elledge uncovered a DNA-damage responsive 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 a wound. Called the DNA damage response, this network senses the problem and sends a signal to the rest of the cell so it can properly repair itself, otherwise severe mutations can occur. As a result, this pathway 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.