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Thomas Graf (biologist)

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Thomas Graf (born 28 September 1944) is a biologist at the Centre for Genomic Regulation (CRG) in Barcelona, Spain. He is a pioneer in cell reprogramming, showing that blood cells can be transdifferentiated by transcription factors.[1][2] He is also known for his early work on oncogenes carried by retroviruses and oncogene cooperation in leukemia formation.[3]

Thomas Graf
Born (1944-09-28) 28 September 1944 (age 80)
Vienna, Austria
Alma materUniversity of Tübingen
Scientific career
Fieldsstem cells biology
InstitutionsEuropean Molecular Biology Laboratory, Albert Einstein College of Medicine, Centre for Genomic Regulation

Research

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In the late 70s Graf co-discovered several cell-derived oncogenes acquired by avian retroviruses, designated Mac (later changed into Myc), Erb and Myb.[4] He found that several naturally occurring virus strains have acquired various pairwise combinations of oncogenes and that these cooperate to cause acute leukemia,[5] an early example for the multigenic origin of cancers. He also showed that the transcription factor Myb can reversibly block the differentiation of white blood cells, one of the first demonstrations of induced cell fate changes.[6] In his more recent research he showed that different types of specialized blood cells can be induced to convert into each other by forced transcription factor expression.[7] In 1995 he pioneered this technique permitting the transdifferentiation of white blood cells into red blood cell precursors and vice versa induced by Gata1[8] and PU.1, respectively. Later (2004) he managed to convert B lymphocytes into functional macrophages, using C/EBPa as a driver.[9] Using the same approach he was also first to induce a conversion of more distantly related cells, namely that of non-blood cells into macrophages.[10] Finally, he found that forced C/EBPa expression in malignant lymphocyte precursors leads to the formation of macrophages and loss of tumorigenicity,[11] suggesting transdifferentiation as an alternative avenue for therapeutic interventions.

Awards

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  • 1983 Wilhelm-Warner-Foundation Award
  • 1983 Main Award, German Society for Microbiology and Hygiene
  • 1983 Kind-Philipp-Foundation Leukemia Research Award
  • 1988 Josef-Steiner-Foundation Prize
  • 1988 Theodor Boveri Lecture and Award
  • 1989 Paul Ehrlich-Ludwig Darmstaedter Prize

References

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  1. ^ Graf, Thomas (2011-12-02). "Historical Origins of Transdifferentiation and Reprogramming". Cell Stem Cell. 9 (6): 504–516. doi:10.1016/j.stem.2011.11.012. ISSN 1934-5909. PMID 22136926.
  2. ^ Baker, Monya (2008-10-23). "Thomas Graf: Cellular identity and transdifferentiation". Nature Reports Stem Cells: 1. doi:10.1038/stemcells.2008.140.
  3. ^ Metz, T.; Graf, T. (1991-07-12). "Fusion of the nuclear oncoproteins v-Myb and v-Ets is required for the leukemogenicity of E26 virus". Cell. 66 (1): 95–105. doi:10.1016/0092-8674(91)90142-L. ISSN 0092-8674. PMID 2070421. S2CID 29746161.
  4. ^ Roussel, M.; Saule, S.; Lagrou, C.; Rommens, C.; Beug, H.; Graf, T.; Stehelin, D. (1979-10-11). "Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation". Nature. 281 (5731): 452–455. Bibcode:1979Natur.281..452R. doi:10.1038/281452a0. PMID 226888. S2CID 4371767.
  5. ^ Graf, Thomas; Beug, Hartmut (1983-08-01). "Role of the v-erbA and v-erbB oncogenes of avian erythroblastosis virus in erythroid cell transformation". Cell. 34 (1): 7–9. doi:10.1016/0092-8674(83)90130-7. ISSN 0092-8674. PMID 6309413. S2CID 41243358.
  6. ^ Beug, H.; Blundell, P. A.; Graf, T. (May 1987). "Reversibility of differentiation and proliferative capacity in avian myelomonocytic cells transformed by tsE26 leukemia virus". Genes & Development. 1 (3): 277–286. doi:10.1101/gad.1.3.277. ISSN 0890-9369. PMID 2824281.
  7. ^ Graf, Thomas; Enver, Tariq (2009). "Forcing cells to change lineages". Nature. 462 (7273): 587–594. Bibcode:2009Natur.462..587G. doi:10.1038/nature08533. PMID 19956253. S2CID 4417323.
  8. ^ Kulessa, H.; Frampton, J.; Graf, T. (1995-05-15). "GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts". Genes & Development. 9 (10): 1250–1262. doi:10.1101/gad.9.10.1250. ISSN 0890-9369. PMID 7758949.
  9. ^ Xie, Huafeng; Ye, Min; Feng, Ru; Graf, Thomas (2004-05-28). "Stepwise Reprogramming of B Cells into Macrophages". Cell. 117 (5): 663–676. doi:10.1016/S0092-8674(04)00419-2. ISSN 0092-8674. PMID 15163413.
  10. ^ Feng, R.; Desbordes, S. C.; Xie, H.; Tillo, E. S.; Pixley, F.; Stanley, E. R.; Graf, T. (2008). "PU.1 and C/EBP / convert fibroblasts into macrophage-like cells". Proceedings of the National Academy of Sciences. 105 (16): 6057–6062. doi:10.1073/pnas.0711961105. PMC 2327209. PMID 18424555.
  11. ^ Rapino, Francesca; Robles, Eloy F.; Richter-Larrea, Jose A.; Kallin, Eric M.; Martinez-Climent, Jose A.; Graf, Thomas (2013-04-25). "C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity". Cell Reports. 3 (4): 1153–1163. doi:10.1016/j.celrep.2013.03.003. ISSN 2211-1247. PMID 23545498.
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