Repairing the Crosslink: From Molecular Mechanism to Cancer Prevention
Event Details
- Type
- Monday Lecture Series
- Speaker(s)
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Agata Smogorzewska, M.D., Ph.D., Skoler Horbach Family Professor and head, Laboratory of Genome Maintenance, The Rockefeller University
- Speaker bio(s)
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DNA interstrand crosslinks are covalent linkages between the two strands of the DNA double helix that block replication and transcription. If left unrepaired, these lesions are lethal or mutagenic to cells. They are resolved during DNA replication by a tightly coordinated repair pathway involving the FANC proteins. Loss of this pathway in humans causes Fanconi anemia, a multi-system disorder marked by developmental malformations, bone marrow failure, infertility, and a striking predisposition to cancers of many types. This lecture will present recent advances in understanding the cellular origins of interstrand crosslinks, the mechanism of their repair, the genetic basis of the disorder's diverse clinical manifestations, premalignant clonal changes detectable within the oral mucosa, and how these insights are now being translated into a cancer prevention trial.
Agata Smogorzewska is the Skoler Horbach Family Professor and Head of the Laboratory of Genome Maintenance at The Rockefeller University in New York City. She earned her MD-PhD through the Tri-Institutional MD-PhD Program in New York, completing her thesis work in the laboratory of Prof. Titia de Lange, where she cloned and characterized TRF2, telomeric protein essential for protecting chromosome ends. After a residency in clinical pathology at Massachusetts General Hospital, she pursued postdoctoral training at Harvard Medical School with Prof. Stephen Elledge, where she began her work on the DNA interstrand crosslink repair pathway. She joined The Rockefeller University as an assistant professor in 2009. Research in the Smogorzewska laboratory focuses on DNA repair during replication. Using Fanconi anemia and other genetic diseases as a model, her group seeks to elucidate the pathways that preserve organ function and prevent cancer, with particular emphasis on those that replicate and repair DNA. She is especially passionate about understanding the pathogenesis of Fanconi anemia–associated cancers and leverages the International Fanconi Anemia Registry to advance insight into the disease. Agata is the recipient of numerous honors, including Harold M. Weintraub Graduate Student Award, Burroughs Wellcome Fund Career Award for Medical Scientists, the Doris Duke Charitable Foundation Clinical Scientist Development Award. She has served as a Howard Hughes Medical Institute Faculty Scholar and was elected to the American Society for Clinical Investigation (ASCI) in 2016.
- Open to
- Campus Only