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Alan D. D'Andrea, MD


Radiation Oncology


Alan D. D

Researcher

  • Director, Susan F. Smith Center for Women's Cancers
  • Director of the Center for DNA Damage and Repair
  • Alvan T. and Viola D. Fuller American Cancer Society Professor of Radiation Oncology, Harvard Medical School

Clinical Interests

  • Cancer susceptibility
  • Fanconi anemia
  • Gene therapy
  • Genetic risk

Contact Information

  • Office Phone Number617-632-2112
  • Fax617-632-6069

Bio

Dr. D’Andrea received his Doctor of Medicine from Harvard Medical School in 1983. He completed his residency at the Children’s Hospital of Philadelphia, and a fellowship in pediatric hematology-oncology at Dana-Farber Cancer Institute and Boston Children’s Hospital. He also completed a research fellowship at the Whitehead Institute of Biomedical Research at Massachusetts Institute of Technology, where he cloned the receptor for erythropoietin, the major hormone for blood production. Dr. D’Andrea joined the Dana-Farber faculty in 1990. He is currently the Fuller-American Cancer Society Professor of Radiation Oncology at Harvard Medical School, the Director of the Center for DNA Damage and Repair, and the Director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute.

Dr. D’Andrea is internationally known for his research in the area of DNA damage and DNA repair. His laboratory also investigates the pathogenesis of Fanconi Anemia, a human genetic disease characterized by a DNA repair defect, bone marrow failure, and cancer predisposition.

A recipient of numerous academic awards, Dr. D’Andrea is a former Stohlman Scholar of the Leukemia and Lymphoma Society, a Distinguished Clinical Investigator of the Doris Duke Charitable Trust, a recipient of the E. Mead Johnson Award from the Society for Pediatric Research, a recipient of the G.H.A. Clowes Memorial Award from the American Association for Cancer Research, a Fellow of the American Association for the Advancement of Science, a member of the American Association for Cancer Research Academy, the National Academy of Medicine, and the National Academy of Sciences.

Board Certification:

  • Pediatrics

Fellowship:

  • Boston Children's Hospital/Dana-Farber Cancer Institute

Residency:

  • Children's Hospital of Philadelphia

Medical School:

  • Harvard Medical School

Recent Awards:

  • Award of Merit, Fanconi Anemia Scientific Symposium 2002
  • E. Mead Johnson Award for Research in Pediatrics, Society for Pediatric Research 2001
  • Excellence in Research Award, American Academy of Pediatrics 1997
  • Member, National Academy of Medicine (NAM), 2017
  • Fellow, American Association for Cancer Research Academy, 2020
  • Member, National Academy of Sciences (NAS), 2021

Research

Chromosome Instability and Susceptibility to Cancer

Our laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors.Our primary focus is the molecular pathogenesis of the human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS). FA is an autosomal-recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents. Seven FA genes have been cloned, and the encoded FA proteins interact in a novel signaling pathway. Five FA proteins (A, C, E, F, G) form a nuclear protein complex required for the monoubiquitination of the D2 protein. Activated D2 is targeted to chromatin, where it interacts with the BRCA1 and BRCA2 breast-cancer susceptibility gene products. Our research program addresses several aspects of this novel signaling pathway, including (1) the assembly, transport, and structure of the FA protein complex; (2) the enzymatic monoubiquitination and deubiquitination of the D2 protein; (3) the function of the chromatin-associated FA complex in cell cycle checkpoints and homologous recombination DNA repair; and (4) the identification of novel interacting proteins in these complexes.

New HV, Cale CM, Tischkowitz M, Jones A, Telfer P, Veys P, D'Andrea AD, Mathew CG, Hann I. Nijmegen breakage syndrome diagnosed as Fanconi anaemia. Pediatr Blood Cancer 2005;44:494-9.

Nakanishi K, Yang YG, Pierce AJ, Taniguchi T, Digweed M, D'Andrea AD, Wang ZQ, Jasin M. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc Natl Acad Sci U S A 2005;102:1110-5.

Howlett NG, Taniguchi T, Durkin SG, D'Andrea AD, Glover TW. The Fanconi anemia pathway for the DNA replication stress response at regulation of common fragile site stability. Hum Mol Genet 2005;14:693-701.

Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RV, D'Andrea AD, Bernards R. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol Cell 2005;17:331-9.

Soulier J, Leblanc T, Larghero J, Dastot H, Shimamura A, Guardiola P, Esperou H, Ferry C, Jubert C, Feugeas JP, Henri A, Toubert A, Socie G, Baruchel A, Sigaux F, D'Andrea AD, Gluckman E. Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 2005;105:1329-36.

Andreassen PR, D'Andrea AD, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev 2004;18:1958-63.

Wang X, Andreassen PR, D'Andrea AD. Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol 2004;24:5850-62.

Montes de Oca R, Gregory R, Taniguchi T, Wang X, Andreassen P, Margossian S, Grompe M, Houghtaling S, D'Andrea AD. Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood 2005;105:1003-9.

D'Andrea AD, Grompe M. The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 2003;3:23-34.

Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, Mok SC, D'Andrea AD. Disruption of the Fanconi anemia/BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003;9:568-74.

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