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BCRF Grantee Since

2003

Donor Recognition

The Bloomingdale's Award

Area(s) of Focus

Titia de Lange, PhD

Head, Laboratory of Cell Biology and Genetics
Leon Hess Professor
American Cancer Society Professor
The Rockefeller University
New York, New York

Current Research

Cancer genome sequencing efforts have illuminated the horrific genomic alterations underlying human breast cancer. Over the past years, Dr. de Lange's group has provided evidence that the gradual loss of telomere function and the resulting telomere crisis can explain much of the genome instability in the early stages of breast cancer development. Their current efforts are focused on two distinct but related projects. First, they are developing a molecular signature for telomere crisis, allowing the identification of human tumors that have experienced this type of genome instability in their proliferative history so that investigators can harness the therapeutic and diagnostic potential associated with this aspect of tumorigenesis. Second, Dr. de Lange's team has recently discovered that Rif1 is responsible for the maximal sensitivity of BRCA1-deficient breast cancer to the PARP1 inhibitor class of drugs. They have shown that Rif1 acts by altering the processing of double-stranded breaks, blocking nucleases that prepare DNA ends for repair by homologous recombination. Their current efforts are focused on the mechanism by which Rif1 acts and other pathways that could contribute to the sensitivity of BRCA1-deficient breast cancers to PARP1 inhibitors.

Mid-Year Summary

Cancer genome sequencing efforts have illuminated the horrific genomic alterations underlying human breast cancer. The current efforts of Dr. de Lange’s laboratory are focused on two distinct but related projects. First, they are developing a molecular signature for telomere crisis, allowing identification of human tumors that have experienced this type of genome instability in their proliferative history so that the researchers can harness the therapeutic and diagnostic potential associated with this aspect of tumorigenesis. Second, they are following up on their discovery that Rif1 is responsible for the maximal sensitivity of BRCA1-deficient breast cancer to the PARP1 inhibitor class of drugs that are currently studied in the clinic. The de Lange team has shown that Rif1 acts by altering the processing of double-stranded breaks, blocking nucleases that prepare DNA ends for repair by homologous recombination. They have made significant progress in better understanding the mechanism by which Rif1 acts and other pathways that could contribute to the sensitivity of BRCA1-deficient breast cancers to PARP1 inhibitors.

Bio

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 University of North Carolina 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.

Dr. de Lange earned the Dutch equivalent of a master's of science degree from the University of Amsterdam and the National Institute for Medical Research in London, and a doctorate in biochemistry from the University of Amsterdam and The Netherlands Cancer Institute. From 1985 to 1990, she was a postdoctoral fellow in the laboratory of Dr. Harold Varmus at the University of California, San Francisco, 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. Her work is focused on the function of human telomeres and the sources of genomic instability in cancer.

Dr. de Lange is an elected member of the Dutch Royal Academy of Sciences, the European Molecular Biology Organization, the U.S. 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 Clowes Award of the American Association of Cancer Research, the 2011 Vilcek Prize for Biomedical Science, and the Heineken Prize from the Royal Dutch Academy for Arts and Sciences. In 2013, Dr. de Lange was one of the 11 inaugural recipients of the Breakthrough Prize in Life Sciences. She also received The Breast Cancer Research Foundation’s 2013 Jill Rose Award for research excellence.

Dr. de Lange was the first woman to receive the Dr. H.P. Heineken Prize for Biochemistry and Biophysics, presented by the Royal Netherlands Academy for Arts and Sciences. Read More. 

Read more about Dr. de Lange in her profile in the National Cancer Institute's Cancer Bulletin 

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