Alan D'Andrea

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Alan D'Andrea
BornSeptember 28, 1956 (1956-09-29) (aged 1946)
Pasadena, California, U.S.
Alma mater Harvard University, Harvard Medical School
AwardsMember, National Academy of Medicine, 2017; Fellow, American Association for the Advancement of Science (AAAS), 2012; 52nd Annual AACR G.H.A. Clowes Memorial Award, 2012.
Scientific career
Fields Cancer research, oncology, hematology
InstitutionsHarvard Medical School, Dana Farber Cancer Institute

Alan D. D'Andrea is an American cancer researcher and the Fuller American Cancer Society Professor of Radiation Oncology at Harvard Medical School. D'Andrea's research at the Dana Farber Cancer Institute focuses on chromosome instability and cancer susceptibility. He is currently the director of the Center for DNA Damage and Repair and the director of the Susan F. Smith Center for Women's Cancer.

Contents

As a postdoctoral fellow at the Whitehead Institute of Biomedical Research in Cambridge, Massachusetts, D'Andrea cloned the erythropoietin receptor, a protein known to rescue red blood cell progenitors from apoptosis. [1]

Research

The D’Andrea laboratory at the Dana Farber Cancer Institute focuses on the molecular events involved in normal blood cell formation and on the molecular cause of leukemia and other cancers. His laboratory examines molecular signaling pathways and the resulting DNA damage response in mammalian cells. These pathways are often disrupted in cancer cells, accounting for chromosome instability and increased gene mutation frequency in human tumors. D'Andrea and his colleagues have identified and cloned a family of cytokine-inducible deubiquitinating enzymes that regulate hematopoietic cell growth by controlling the ubiquitin-mediated proteolysis of intracellular growth regulatory proteins. [2]

The practical application of D'Andrea's research includes genetic diseases in humans. His primary focus is the molecular pathogenesis of human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS). Most notably, Fanconi anemia is an autosomal-recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents.

D'Andrea's laboratory contributed significantly to the elucidation of a new DNA repair pathway, the FA/BRCA pathway, and demonstrated that one of the FA genes (FANCD1) is identical to the breast cancer gene, BRCA2. [3] Somatic disruption of genes in the FA/BRCA pathway account for the chromosome instability and drug sensitivity of many solid tumors in the general population including breast, ovarian, prostate, and pancreatic cancers. [4]

Background

D’Andrea received his MD in 1983 from Harvard Medical School, residency training in pediatric at Children's Hospital of Philadelphia, and fellowship training in hematology–oncology at the Dana Farber Cancer Institute and Children’s Hospital Boston. He completed a research fellowship at the Whitehead Institute of Biomedical Research and joined the Dana Farber Cancer Institute in 1990.

Awards

Personal

D'Andrea attended the Lawrenceville School in Lawrenceville, New Jersey and Harvard University. He lives in Gloucester, Massachusetts with his wife and dog. He has two children. He is the brother of Laura Tyson, an American economist and former Chair of the US President's Council of Economic Advisers during the Clinton Administration.

Related Research Articles

<span class="mw-page-title-main">Fanconi anemia</span> Medical condition

Fanconi anemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.

<span class="mw-page-title-main">BRCA2</span> Gene known for its role in breast cancer

BRCA2 and BRCA2 are a human gene and its protein product, respectively. The official symbol and the official name are maintained by the HUGO Gene Nomenclature Committee. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other vertebrate species. BRCA2 is a human tumor suppressor gene, found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.

<span class="mw-page-title-main">Fanconi anemia, complementation group C</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group C protein is a protein that in humans is encoded by the FANCC gene. This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.

<span class="mw-page-title-main">FANCA</span> Protein-coding gene in the species Homo sapiens

Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the FANCA gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.

<span class="mw-page-title-main">FANCG</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.

<span class="mw-page-title-main">FANCF</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.

<span class="mw-page-title-main">FANCE</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the FANCE gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation groufcrp E.

<span class="mw-page-title-main">FANCL</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

<span class="mw-page-title-main">FANCB</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.

<span class="mw-page-title-main">USP1</span> Protein-coding gene in the species Homo sapiens

Ubiquitin carboxyl-terminal hydrolase 1 is an enzyme that in humans is encoded by the USP1 gene.

<span class="mw-page-title-main">FANCI</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene. Mutations in the FANCI gene are known to cause Fanconi anemia.

<span class="mw-page-title-main">PALB2</span> Protein-coding gene in the species Homo sapiens

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.

Simon Joseph Boulton is a British scientist who has made important contributions to the understanding of DNA repair and the treatment of cancer resulting from DNA damage. He currently occupies the position of Senior Scientist and group leader of the DSB Repair Metabolism Laboratory at the Francis Crick Institute, London. He is also an honorary Professor at University College London.

<span class="mw-page-title-main">Hereditary cancer syndrome</span> Inherited genetic condition that predisposes a person to cancer

A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

<span class="mw-page-title-main">FAN1</span> Protein-coding gene in the species Homo sapiens

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

Ashok Venkitaraman is a British cancer researcher of Indian origin. He is the Director of the Cancer Science Institute of Singapore, a Distinguished Professor of Medicine at the National University of Singapore, and Program Director at A*STAR, Singapore. From 1998 to 2020, he was the inaugural holder of the Ursula Zoellner Professorship of Cancer Research at the University of Cambridge, a Professorial Fellow at Pembroke College, Cambridge, and from 2006 to 2019, was the Director of the Medical Research Council Cancer Unit

<span class="mw-page-title-main">Ketan J. Patel</span>

Ketan Jayakrishna Patel is a British-Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).

<span class="mw-page-title-main">Double-strand break repair model</span>

A double-strand break repair model refers to the various models of pathways that cells undertake to repair double strand-breaks (DSB). DSB repair is an important cellular process, as the accumulation of unrepaired DSB could lead to chromosomal rearrangements, tumorigenesis or even cell death. In human cells, there are two main DSB repair mechanisms: Homologous recombination (HR) and non-homologous end joining (NHEJ). HR relies on undamaged template DNA as reference to repair the DSB, resulting in the restoration of the original sequence. NHEJ modifies and ligates the damaged ends regardless of homology. In terms of DSB repair pathway choice, most mammalian cells appear to favor NHEJ rather than HR. This is because the employment of HR may lead to gene deletion or amplification in cells which contains repetitive sequences. In terms of repair models in the cell cycle, HR is only possible during the S and G2 phases, while NHEJ can occur throughout whole process. These repair pathways are all regulated by the overarching DNA damage response mechanism. Besides HR and NHEJ, there are also other repair models which exists in cells. Some are categorized under HR, such as synthesis-dependent strain annealing, break-induced replication, and single-strand annealing; while others are an entirely alternate repair model, namely, the pathway microhomology-mediated end joining (MMEJ).

Bing Xia is a Chinese American scientist and professor at the Rutgers Cancer Institute of New Jersey, where he directs the Xia Laboratory. He is best known for his discovery of the PALB2 tumor suppressor gene, a notable scientific advance in the field of cancer genetics.

References

  1. ↑ D'Andrea, A. D.; Lodish, H. F.; Wong, G. G. (1989-04-21). "Expression cloning of the murine erythropoietin receptor". Cell. 57 (2): 277–285. doi:10.1016/0092-8674(89)90965-3. ISSN   0092-8674. PMID   2539263. S2CID   33953292.
  2. ↑ Zhu, Y; Carroll, M; Papa, F R; Hochstrasser, M; D'Andrea, A D (1996-04-16). "DUB-1, a deubiquitinating enzyme with growth-suppressing activity". Proceedings of the National Academy of Sciences of the United States of America. 93 (8): 3275–3279. Bibcode:1996PNAS...93.3275Z. doi: 10.1073/pnas.93.8.3275 . ISSN   0027-8424. PMC   39596 . PMID   8622927.
  3. ↑ Howlett, Niall G.; Taniguchi, Toshiyasu; Olson, Susan; Cox, Barbara; Waisfisz, Quinten; De Die-Smulders, Christine; Persky, Nicole; Grompe, Markus; Joenje, Hans; Pals, Gerard; Ikeda, Hideyuki (2002-07-26). "Biallelic inactivation of BRCA2 in Fanconi anemia". Science. 297 (5581): 606–609. Bibcode:2002Sci...297..606H. doi: 10.1126/science.1073834 . ISSN   1095-9203. PMID   12065746. S2CID   9073545.
  4. ↑ D'Andrea, Alan D. (2010-05-20). "Susceptibility pathways in Fanconi's anemia and breast cancer". The New England Journal of Medicine. 362 (20): 1909–1919. doi:10.1056/NEJMra0809889. ISSN   1533-4406. PMC   3069698 . PMID   20484397.
  5. ↑ "2021 NAS Election". www.nasonline.org. Retrieved 2021-04-28.
  6. ↑ "Ernest Beutler Lecture and Prize Recipients". www.hematology.org. 2019-08-29. Retrieved 2019-10-18.
  7. ↑ "National Academy of Medicine Elects 80 New Members". 16 October 2017.
  8. ↑ "Alan D. D'Andrea, M.D., Receives the 52nd Annual AACR G.H.A. Clowes Memorial Award". Newswire.com. 2012-03-26. Retrieved September 4, 2012.
  9. ↑ "2012 AAAS Fellows" (PDF).
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