Head, Laboratory of Cell Biology and Genetics Leon Hess Professor American Cancer Society Professor The Rockefeller University New York, New York
BRCA1 is one of the most commonly mutated genes that predispose women to breast and ovarian cancer. The function of BRCA1 is to maintain the integrity of DNA, which undergoes a wide variety of damaging events in every cell, every day. Loss or mutation of BRCA1 leads to faulty repair of broken DNA ends and creates changes that can promote cancer progression. On the other hand, the inability of BRCA1-deficient cancer cells to correctly repair DNA damage makes them more vulnerable to certain drugs that cause DNA damage, such as a class of drugs called PARP inhibitors. PARP inhibitors have shown promise in the clinic for the treatment of BRCA1-deficient cancers and other aggressive forms of breast cancers with defects in DNA repair including many triple negative breast cancers. Dr. de Lange’s group previously identified a gene called Rif1 that makes BRCA1-deficient cells very sensitive to PARP inhibitors and has recently discovered a second pathway that is also important to the efficacy of PARP inhibitors. These findings may have important clinical implications for the treatment of BCRA1 breast cancers. In addition, Dr. de Lange’s laboratory has been working to develop a method to monitor genomic alterations in the earliest stages of breast cancer in order to identify new predictive biomarkers.
A major focus of Dr. de Lange's research is to isolate the protein components in human telomeres and understand their roles in the cell. Several years ago, this work yielded an unexpected breakthrough, when Dr. de Lange and a collaborator at the UNC showed that the very tips of human telomeres are not linear, as had been assumed, but instead end in neatly finished loops. The discovery of telomere loops has sparked a reconsideration of many facets of telomere biology, including how these structures are involved in cancer and aging.From 1985 to 1990, Dr. de Lange was a postdoctoral fellow in the laboratory of Dr. Harold Varmus at UCSF, where she was one of the first scientists to isolate human telomeres. Dr. de Lange joined The Rockefeller University in 1990 as an Assistant Professor. She was appointed a tenured Professor in 1997 and the Leon Hess Professor in 1999.
Dr. de Lange is an elected member of the Dutch Royal Academy of Sciences, the European Molecular Biology Organization, the US National Academy of Sciences, the Institute of Medicine, and the American Academy for Arts and Sciences. Among her awards are the inaugural Paul Marks Prize for Cancer Research from Memorial Sloan Kettering Cancer Center, the 2011 Vilcek Prize for Biomedical Science, and the Heineken Prize from the Royal Dutch Academy for Arts and Sciences. In 2013, she was one of the 11 inaugural recipients of the Breakthrough Prize in Life Sciences; she also received the 2014 Canada Gairdner International Award.