AACR G.H.A. Clowes Memorial Award

SPOTLIGHT

52nd Annual Recipient Alan D. D'Andrea, M.D. Alvan T. and Viola D. Fuller American Cancer Society Professor of Radiation Oncology Harvard Medical School Scientific Director, Molecular Diagnostics Laboratory Dana-Farber Cancer Institute Harvard University Boston, MA

Dr. Alan D. D’Andrea’s scientific notoriety began when he cloned the erythropoietin (EPO) receptor during his postdoctoral studies in Harvey Lodish’s laboratory. We now understand that this receptor is one of the vital proteins that regulate red blood cell production (angiogenesis) and survival. The ability of this protein to govern angiogenesis, a process essential to cancer survival, has rendered it an attractive target for cancer therapeutics. Dr. D’Andrea’s continued work involving the EPO receptor is centered around understanding how point mutations and epigenetic modifications of the receptor alter downstream intracellular signaling pathways including the JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) and MAPK (Mitogen-Activated Protein Kinase) signaling pathways within hematological malignancies.

In addition to his work regarding the EPO receptor, Dr. D’Andrea has contributed immensely to our understanding of DNA damage and its effects on chromosomal stability, cell cycle progression and cancer susceptibility. His research has centered on investigating these processes within rare  chromosomal instability syndromes including ataxia telangiectasia, Bloom’s syndrome, and most extensively, Fanconi anemia, which often results in the onset of acute myelogenous leukemia.

In his pursuit to understand DNA repair mechanisms, Dr. D’Andrea initially discovered the Fanconi anemia protein (FANCC; Fanconi Anemia Complementation Group C) involved in the maintenance of chromosomal stability. He later discovered that this protein is one of several that comprise a complex that blocks the deleterious effects of DNA crosslinking agents and maintains chromosomal integrity. His research has since identified that members of the Fanconi anemia family of proteins are subject to post-translational modifications that promote their interaction with DNA repair proteins such as ATM (ataxia telangiectasia) and BRCA1 (breast cancer 1, early onset) prior to their recruitment to sites of chromosomal damage. At the time, this was the first evidence to suggest that DNA repair systems cooperated with chromosomal stability mechanisms within cells.

Subsequent studies demonstrated that not only are Fanconi anemia proteins directly linked to DNA repair mechanisms in the cell, but one such member, FANCD1 is identical to the previously identified breast cancer tumor suppressor gene involved in double-strand DNA break repair, BRCA2. Collectively, these findings are absolutely vital to our continued understanding of cancer progression and survival and have significantly altered our knowledge of DNA instability and repair mechanisms and have showcased the biological relationships present between rare hereditary diseases such as Fanconi anemia and cancer.

Dr. D’Andrea received his M.D. from Harvard Medical School. Afterward, he performed his residency at The Children’s Hospital of Philadelphia within the field of pediatrics and his fellowship back in Boston within the Dana-Farber Cancer Institute and Children’s Hospital of Boston where he concentrated on pediatric hematology and oncology. Later, he conducted his postdoctoral studies at the Whitehead Institute until he returned to the Dana-Farber Cancer Institute and Children’s Hospital of Boston where he has remained, currently serving as the Alvan T. and Viola D. Fuller American Cancer Society professor of radiation oncology, scientific director of the Molecular Diagnostics Laboratory, and director of the Clinical Gene Therapy Center. He has received numerous awards for his research accomplishments including the American Academy of Pediatrics Excellence in Research Award, the E. Mead Johnson Award for Research in Pediatrics, and the Fanconi Anemia Scientific Symposium’s Award of Merit, along with publishing a multitude of papers in high-tiered journals that have been heavily cited for their content.