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A. Thomas Look

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A. Thomas Look is Professor of Pediatrics at Harvard Medical School and Vice-Chair for Research, Pediatric Oncology, Dana–Farber Cancer Institute.[1] He is a pioneer in the use of zebrafish in cancer research and made major contributions to the understanding of leukemia and neuroblastoma biology and pathogenesis.

Education

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Look received a BSE in Chemical Engineering from University of Michigan, Ann Arbor, in 1971, followed by a degree in medicine (MD) from the same university in 1975.[2] He undertook most of his training in pediatric oncology at St. Jude Children's Research Hospital, Memphis, before becoming Professor of Pediatrics at University of Tennessee, College of Medicine in 1987. In 1999 he moved to Dana–Farber Cancer Institute to become Vice Chair for Research in Pediatric Oncology and Professor of Pediatric Oncology at Harvard Medical School.[2]

Honors

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  • 2004 ASCO Pediatric Oncology Lectureship Award, 40th Annual ASCO Mtg, New Orleans, LA.[3]
  • 2005 ASPHO Frank A. Oski Memorial Lectureship Award, May 15, 2005 Annual Mtg., Washington, DC.[4]

Research

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Major discoveries

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  • Discovery of highly recurrent activating Notch mutations in T-ALL (with Jon C. Aster)[5]
  • Discovery of somatic enhancer mutations activating TAL1[6]
  • The first zebrafish model of cancer - MYC-induced T-ALL in the zebrafish[7]
  • Use of gene expression profiling to define distinct oncogenic subgroups in T-ALL[8]
  • Discovery of CHK1 suppressed caspase-2 apoptotic pathway in response to DNA damage[9]
  • Discovery of activating ALK mutations in neuroblastoma[10]
  • Development of FISH to detect MYCN amplification in neuroblastoma[11]
  • Discovery of MET-HGF autocrine axis in AML[12]
  • Core transcriptional circuitry of TAL1 complex[13]
  • Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia[14]
  • Cloning and functional characterization of E2A-HLF in B-ALL[15][16]
  • Discovery of the Slug survival pathway in hematopoietic stem cells[8]
  • Discovery of MYB duplications in T-ALL[17]
  • Discovery of FBXW7 mutations in T-ALL[18]
  • Discovery of MYBL2 as the crucial 20q tumor suppressor in MDS[19]

References

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  1. ^ "A. T. Look, MD - DF/HCC". www.dfhcc.harvard.edu.
  2. ^ a b "A. Thomas Look, MD". Dana-Farber Cancer Institute. Retrieved September 6, 2019.
  3. ^ "All Award Recipients".
  4. ^ "Oski Lectureship · ASPHO".
  5. ^ Weng, Andrew P.; Ferrando, Adolfo A.; Lee, Woojoong; Morris, John P.; Silverman, Lewis B.; Sanchez-Irizarry, Cheryll; Blacklow, Stephen C.; Look, A. Thomas; Aster, Jon C. (8 October 2004). "Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia". Science. 306 (5694): 269–271. Bibcode:2004Sci...306..269W. CiteSeerX 10.1.1.459.5126. doi:10.1126/science.1102160. PMID 15472075. S2CID 24049536.
  6. ^ Mansour, Marc R.; Abraham, Brian J.; Anders, Lars; Berezovskaya, Alla; Gutierrez, Alejandro; Durbin, Adam D.; Etchin, Julia; Lawton, Lee; Sallan, Stephen E.; Silverman, Lewis B.; Loh, Mignon L.; Hunger, Stephen P.; Sanda, Takaomi; Young, Richard A.; Look, A. Thomas (12 December 2014). "An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element". Science. 346 (6215): 1373–1377. Bibcode:2014Sci...346.1373M. doi:10.1126/science.1259037. PMC 4720521. PMID 25394790.
  7. ^ Langenau, David M.; Traver, David; Ferrando, Adolfo A.; Kutok, Jeffery L.; Aster, Jon C.; Kanki, John P.; Lin, Shuo; Prochownik, Ed; Trede, Nikolaus S.; Zon, Leonard I.; Look, A. Thomas (7 February 2003). "Myc-Induced T Cell Leukemia in Transgenic Zebrafish". Science. 299 (5608): 887–890. Bibcode:2003Sci...299..887L. doi:10.1126/science.1080280. PMID 12574629. S2CID 38069481.
  8. ^ a b Inoue, Akira; Seidel, Markus G.; Wu, Wenshu; Kamizono, Shintaro; Ferrando, Adolfo A.; Bronson, Roderick T.; Iwasaki, Hiromi; Akashi, Koichi; Morimoto, Akira; Hitzler, Johann K.; Pestina, Tamara I.; Jackson, Carl W.; Tanaka, Ryuhei; Chong, Miriam J.; McKinnon, Peter J.; Inukai, Takeshi; Grosveld, Gerard C.; Look, A.Thomas (1 October 2002). "Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo". Cancer Cell. 2 (4): 279–288. doi:10.1016/S1535-6108(02)00155-1. PMID 12398892.
  9. ^ Sidi, Samuel; Sanda, Takaomi; Kennedy, Richard D.; Hagen, Andreas T.; Jette, Cicely A.; Hoffmans, Raymond; Pascual, Jennifer; Imamura, Shintaro; Kishi, Shuji; Amatruda, James F.; Kanki, John P.; Green, Douglas R.; D'Andrea, Alan A.; Look, A. Thomas (30 May 2008). "Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3". Cell. 133 (5): 864–877. doi:10.1016/j.cell.2008.03.037. PMC 2719897. PMID 18510930.
  10. ^ George, Rani E.; Sanda, Takaomi; Hanna, Megan; Fröhling, Stefan; II, William Luther; Zhang, Jianming; Ahn, Yebin; Zhou, Wenjun; London, Wendy B.; McGrady, Patrick; Xue, Liquan; Zozulya, Sergey; Gregor, Vlad E.; Webb, Thomas R.; Gray, Nathanael S.; Gilliland, D. Gary; Diller, Lisa; Greulich, Heidi; Morris, Stephan W.; Meyerson, Matthew; Look, A. Thomas (1 October 2008). "Activating mutations in ALK provide a therapeutic target in neuroblastoma". Nature. 455 (7215): 975–978. Bibcode:2008Natur.455..975G. doi:10.1038/nature07397. PMC 2587486. PMID 18923525.
  11. ^ Mathew, Prasad; Valentine, Marcus B; Bowman, Laura C; Rowe, Susan T; Nash, Michael B; Valentine, Virginia A; Cohn, Susan L; Castleberry, Robert P; Brodeur, Garrett M; Look, A Thomas (1 March 2001). "Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study". Neoplasia (New York, N.Y.). 3 (2): 105–109. doi:10.1038/sj.neo.7900146. PMC 1505416. PMID 11420745.
  12. ^ Kentsis, Alex; Reed, Casie; Rice, Kim L; Sanda, Takaomi; Rodig, Scott J; Tholouli, Eleni; Christie, Amanda; Valk, Peter J M; Delwel, Ruud; Ngo, Vu; Kutok, Jeffery L; Dahlberg, Suzanne E; Moreau, Lisa A; Byers, Richard J; Christensen, James G; Woude, George Vande; Licht, Jonathan D; Kung, Andrew L; Staudt, Louis M; Look, A Thomas (10 June 2012). "Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia". Nature Medicine. 18 (7): 1118–1122. doi:10.1038/nm.2819. PMC 3438345. PMID 22683780.
  13. ^ Sanda, Takaomi; Lawton, Lee N.; Barrasa, M. Inmaculada; Fan, Zi Peng; Kohlhammer, Holger; Gutierrez, Alejandro; Ma, Wenxue; Tatarek, Jessica; Ahn, Yebin; Kelliher, Michelle A.; Jamieson, Catriona H.M.; Staudt, Louis M.; Young, Richard A.; Look, A. Thomas (1 August 2012). "Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia". Cancer Cell. 22 (2): 209–221. doi:10.1016/j.ccr.2012.06.007. PMC 3422504. PMID 22897851.
  14. ^ Gutierrez, Alejandro; Pan, Li; Groen, Richard W.J.; Baleydier, Frederic; Kentsis, Alex; Marineau, Jason; Grebliunaite, Ruta; Kozakewich, Elena; Reed, Casie; Pflumio, Francoise; Poglio, Sandrine; Uzan, Benjamin; Clemons, Paul; VerPlank, Lynn; An, Frank; Burbank, Jason; Norton, Stephanie; Tolliday, Nicola; Steen, Hanno; Weng, Andrew P.; Yuan, Huipin; Bradner, James E.; Mitsiades, Constantine; Look, A. Thomas; Aster, Jon C. (9 January 2014). "Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia". Journal of Clinical Investigation. 124 (2): 644–655. doi:10.1172/JCI65093. PMC 3904599. PMID 24401270.
  15. ^ Khatib, Z. A.; Inaba, T.; Valentine, M.; Look, A. T. (15 September 1994). "Chromosomal localization and cDNA cloning of the human DBP and TEF genes". Genomics. 23 (2): 344–351. doi:10.1006/geno.1994.1510. PMID 7835883.
  16. ^ Inaba, T.; Inukai, T.; Yoshihara, T.; Seyschab, H.; Ashmun, R. A.; Canman, C. E.; Laken, S. J.; Kastan, M. B.; Look, A. T. (8 August 1996). "Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor". Nature. 382 (6591): 541–544. Bibcode:1996Natur.382..541I. doi:10.1038/382541a0. PMID 8700228. S2CID 4321391.
  17. ^ O'Neil, Jennifer; Tchinda, Joelle; Gutierrez, Alejandro; Moreau, Lisa; Maser, Richard S.; Wong, Kwok-Kin; Li, Wei; McKenna, Keith; Liu, X. Shirley; Feng, Bin; Neuberg, Donna; Silverman, Lewis; DeAngelo, Daniel J.; Kutok, Jeffery L.; Rothstein, Rodney; DePinho, Ronald A.; Chin, Lynda; Lee, Charles; Look, A. Thomas (24 December 2007). "Alu elements mediate MYB gene tandem duplication in human T-ALL". Journal of Experimental Medicine. 204 (13): 3059–3066. doi:10.1084/jem.20071637. PMC 2150982. PMID 18070937.
  18. ^ O'Neil, Jennifer; Grim, Jonathan; Strack, Peter; Rao, Sudhir; Tibbitts, Deanne; Winter, Christopher; Hardwick, James; Welcker, Markus; Meijerink, Jules P.; Pieters, Rob; Draetta, Giulio; Sears, Rosalie; Clurman, Bruce E.; Look, A. Thomas (6 August 2007). "FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors". Journal of Experimental Medicine. 204 (8): 1813–1824. doi:10.1084/jem.20070876. PMC 2118656. PMID 17646409.
  19. ^ Heinrichs, Stefan; Conover, Lillian F; Bueso-Ramos, Carlos E; Kilpivaara, Outi; Stevenson, Kristen; Neuberg, Donna; Loh, Mignon L; Wu, Wen-Shu; Rodig, Scott J; Garcia-Manero, Guillermo; Kantarjian, Hagop M; Look, A Thomas (16 July 2013). "MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy". eLife. 2: e00825. doi:10.7554/eLife.00825. PMC 3713455. PMID 23878725.
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