David M. Livingston, MD
Emil Frei Professor of Genetics and Medicine
Harvard Medical School
Dana-Farber Cancer Institute
2013-2014 BCRF Project:
Dr. Livingston’s BCRF-funded research centers on the BRCA1 gene, one of the genes commonly associated with breast cancer. In one study, he continues to focus on one specific function of the BRCA1 Breast Cancer (BrCa) suppressor gene that appears to be defective in fresh, ostensibly normal, primary mammary epithelial cells derived from women carrying BRCA1 breast cancer- promoting mutations. It is an inability to repair DNA damage arising defective replication of these cells. A growing body of evidence also implies that this defect plays a leading role in driving normal mammary cells to a cancerous outcome. If proven, this hypothesis could lead to rational, new approaches to mechanism-based BRCA1 BrCa prevention.
In a second project, Dr. Livingston is studying BRCA1-IRIS, which is encoded by the BRCA1 gene but whose actions resemble those of a cancer- promoting rather than a cancer-suppressing protein. Dr. Livingston’s team has collected abundant evidence pointing to the overproduction of BRCA1-IRIS in ~25% of sporadic breast cancers. Where tested in BRCA1-IRIS overproducing BrCa cells, it appears, surprisingly, that this protein stimulates the ability of these cells to metastasize. Since BRCA1-IRIS is a naturally occurring metastasis- promoting protein, it has become a new target of potential therapeutic opportunity.
In the past few months, Dr. Livingston’s group has confirmed their earlier finding that apparently normal breast cells of tumor-free, BRCA1 mutation- bearing women are not functionally normal. Indeed, they now know that these cells cannot perform one of the 8 different BRCA1 functions. In tumor cells, all are abnormal, having been lost late in the tumor development process. This strongly suggests that the single abnormal function of BRCA1 present in mutation-carrying, ostensibly normal mammary gland cells may be a primary driver of BRCA1 BrCa development. Interfering with this abnormality is one logical approach to eliciting a state of BRCA1 BrCa prevention.
Dr. Livingston received his A.B. from Harvard in 1961 and his M.D. from Tufts Medical School in 1965. He undertook his clinical training in internal medicine at Peter Bent Brigham Hospital and his scientific training at the NCI and at Harvard Medical School. He joined the Harvard faculty as Assistant Professor of Medicine in 1973 and has been a faculty member at HMS and at DFCI continuously since that time. He is now the Emil Frei Professor of Genetics and Medicine at HMS and DFCI, where he serves as Chair of the Executive Committee for Research; Director of The Charles A. Dana Division of Human Cancer Genetics; and Deputy Director of the Dana-Farber/Harvard Cancer Center.
Dr. Livingston served as Director and Physician-in-Chief at DFCI from 1991-1995 and Chair, Board of Scientific Advisors at the National Cancer Institute (1995-1999). He was elected to the Institute of Medicine of the National Academy of Sciences in 1990 and, in 1995, he was elected to the National Academy of Sciences. He is also a member of the American Academy of Arts and Sciences. In 1997, he received the Award for Distinguished Research in the Biomedical Sciences from the Association of American Medical Colleges and the Brinker International Award for Breast Cancer Research. In 2005, he received the Clowes Award for excellence in cancer research of the American Association for Cancer Research and the Theodor Boveri Award from the German Cancer Society.