A leader in expanding our understanding of how a cell responds when its DNA is damaged, Dr. de Lange focuses her research on how telomeres protect chromosome ends and is widely recognized as having defined this field. She initially identified a binding factor at telomeres that she called TRF1. In a decade of exacting research, she and her colleagues identified TRF2 and a multi-subunit protein complex containing TRF1 and TRF2 that they named shelterin. By protecting chromosome ends from the DNA damage response, shelterin prevents the type of genome instability that can disrupt normal cell growth and promote cancer.
Dr. de Lange’s group has determined that different components of shelterin are dedicated to the repression of distinct pathways. She and a collaborator showed that the ends of telomeres are not linear, as had been thought, but end in t-loops, which hide the telomere terminus from the DNA damage response. She showed how the TRF2 component of shelterin generates t-loops to protect chromosome ends from DNA repair. Her group is now working to determine the mechanism by which each shelterin protein inhibits its designated pathway and how loss of telomere protection contributes to genome instability in cancer.
Career Highlights
2013 Breakthrough Prize in Life Sciences
2012 Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Sciences, Amsterdam
2011 Vilcek Prize for Creative Promise in Biomedical Sciences
2010 Elected Member, Institute of Medicine
2010 AACR-G.H.A. Clowes Memorial Award
2007 Elected Fellow, American Association for the Advancement of Science
2007 Elected Fellow, American Academy of Arts and Sciences
2006 Elected Fellow, American Academy of Microbiology
2006 Elected Foreign Associate, National Academy of Sciences, Washington, D.C.
2004 AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship
2001 First Paul Marks Prize for Cancer Research, Memorial Sloan-Kettering Cancer Center
2000 Elected Member, Royal Dutch Academy of Sciences
1985 PhD, University of Amsterdam