Research Overview

The Gutierrez laboratory is focused on discovery of molecular oncogenesis and novel therapeutic targets for chemoresistant human cancers, including high-risk T-cell acute lymphoblastic leukemia and treatment-resistant sarcomas. Our approach combines functional genetics, biochemistry and small molecule screens, leveraging the zebrafish models of these high-risk human cancers we have recently developed.

For more information, visit our lab website: theaglab.com.

About Dr. Alejandro Gutierrez

Dr. Gutierrez received an MD degree from the University of Pennsylvania School of Medicine and completed a pediatrics residency at The Children's Hospital of Philadelphia, followed by a fellowship in pediatric hematology/oncology at Boston Children's Hospital/Dana-Farber Cancer Institute. His postdoctoral research training was with Dr. A. Thomas Look at Dana-Farber Cancer Institute. Dr. Gutierrez is a Scholar of the American Society of Hematology-Harold Amos Medical Faculty Development Program and recipient of the 2010 Young Investigator Award from the American Society of Pediatric Hematology/Oncology.

Researcher Services

Researcher Areas

  • Hematology/Oncology

Research Departments

Research Divisions

Researcher Centers

Researcher Labs

PUBLICATIONS

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  1. Mansour MR, He S, Li Z, Lobbardi R, Abraham BJ, Hug C, Rahman S, Leon TE, Kuang YY, Zimmerman MW, Blonquist T, Gjini E, Gutierrez A, Tang Q, Garcia-Perez L, Pike-Overzet K, Anders L, Berezovskaya A, Zhou Y, Zon LI, Neuberg D, Fielding AK, Staal FJT, Langenau DM, Sanda T, Young RA, Look AT. JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. J Exp Med. 2018 Jul 02; 215(7):1929-1945. View abstract
  2. Burns MA, Liao ZW, Yamagata N, Pouliot GP, Stevenson KE, Neuberg DS, Thorner AR, Ducar M, Silverman EA, Hunger SP, Loh ML, Winter SS, Dunsmore KP, Wood B, Devidas M, Harris MH, Silverman LB, Sallan SE, Gutierrez A. Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia. Leukemia. 2018 Mar 20. View abstract
  3. Cooper ML, Choi J, Staser K, Ritchey JK, Devenport JM, Eckardt K, Rettig MP, Wang B, Eissenberg LG, Ghobadi A, Gehrs LN, Prior JL, Achilefu S, Miller CA, Fronick CC, O'Neal J, Gao F, Weinstock DM, Gutierrez A, Fulton RS, DiPersio JF. An "off-the-shelf" fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia. 2018 Feb 20. View abstract
  4. Gutierrez A, Kentsis A. Acute myeloid/T-lymphoblastic leukaemia (AMTL): a distinct category of acute leukaemias with common pathogenesis in need of improved therapy. Br J Haematol. 2018 Mar; 180(6):919-924. View abstract
  5. Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn JS, Abraham BJ, Namiki Y, Mansour M, Abdelfattah NS, Molodtsov A, Alexe G, Toiber D, de Waard M, Jain E, Boukhali M, Lion M, Bhere D, Shah K, Gutierrez A, Stegmaier K, Silverman LB, Sadreyev RI, Asara JM, Oettinger MA, Haas W, Look AT, Young RA, Mostoslavsky R, Dellaire G, Langenau DM. TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2017 11; 7(11):1336-1353. View abstract
  6. Simón-Carrasco L, Graña O, Salmón M, Jacob HKC, Gutierrez A, Jiménez G, Drosten M, Barbacid M. Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma. Genes Dev. 2017 07 15; 31(14):1456-1468. View abstract
  7. Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View abstract
  8. Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View abstract
  9. Harrison NR, Laroche FJ, Gutierrez A, Feng H. Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights. Adv Exp Med Biol. 2016; 916:335-69. View abstract
  10. Knoechel B, Bhatt A, Pan L, Pedamallu CS, Severson E, Gutierrez A, Dorfman DM, Kuo FC, Kluk M, Kung AL, Zweidler-McKay P, Meyerson M, Blacklow SC, DeAngelo DJ, Aster JC. Complete hematologic response of early T-cell progenitor acute lymphoblastic leukemia to the ?-secretase inhibitor BMS-906024: genetic and epigenetic findings in an outlier case. Cold Spring Harb Mol Case Stud. 2015 Oct; 1(1):a000539. View abstract
  11. Suarez A, Piña M, Nichols-Vinueza DX, Lopera J, Rengifo L, Mesa M, Cardenas M, Morrissey L, Veintemilla G, Vizcaino M, Del Toro L, Vicuna V, Fernandez J, Neuberg D, Stevenson K, Gutierrez A. A strategy to improve treatment-related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays. Pediatr Blood Cancer. 2015 Aug; 62(8):1395-402. View abstract
  12. Ariës IM, Gutierrez A. An X-linked tumor suppressor in T-ALL. Blood. 2015 Jan 01; 125(1):3-4. View abstract
  13. Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, Loh ML, Hunger SP, Sanda T, Young RA, Look AT. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 2014 Dec 12; 346(6215):1373-7. View abstract
  14. Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour MR, Liu L, Wang H, King B, Shaik S, Gutierrez A, Ordureau A, Otto T, Kreslavsky T, Baitsch L, Bury L, Meyer CA, Ke N, Mulry KA, Kluk MJ, Roy M, Kim S, Zhang X, Geng Y, Zagozdzon A, Jenkinson S, Gale RE, Linch DC, Zhao JJ, Mullighan CG, Harper JW, Aster JC, Aifantis I, von Boehmer H, Gygi SP, Wei W, Look AT, Sicinski P. Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol. 2014 Nov; 16(11):1080-91. View abstract
  15. Pouliot GP, Gutierrez A. Thymocyte transformation enhanced. Nat Med. 2014 Oct; 20(10):1096-7. View abstract
  16. Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, Loh ML, Hunger SP, Wood B, DeAngelo DJ, Stone R, Harris M, Gutierrez A, Kelliher MA, Letai A. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014 Sep; 4(9):1074-87. View abstract
  17. Nichols-Vinueza DX, Gutierrez A, Veintemilla G, Perez-Atayde AR. Letter to the editor: Pseudopapillary tumor of the pancreas in a child with hemihypertrophy and a history of Wilms tumor. Pediatr Blood Cancer. 2014 Oct; 61(10):1901-2. View abstract
  18. Gutierrez A, Feng H, Stevenson K, Neuberg DS, Calzada O, Zhou Y, Langenau DM, Look AT. Loss of function tp53 mutations do not accelerate the onset of myc-induced T-cell acute lymphoblastic leukaemia in the zebrafish. Br J Haematol. 2014 Jul; 166(1):84-90. View abstract
  19. Gutierrez A, Roderick JE, Kelliher MA. Leukemia propagating cells Akt up. Cancer Cell. 2014 Mar 17; 25(3):263-5. View abstract
  20. Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014 Apr; 46(4):364-70. View abstract
  21. Gutierrez A, Pan L, Groen RW, Baleydier F, Kentsis A, Marineau J, Grebliunaite R, Kozakewich E, Reed C, Pflumio F, Poglio S, Uzan B, Clemons P, VerPlank L, An F, Burbank J, Norton S, Tolliday N, Steen H, Weng AP, Yuan H, Bradner JE, Mitsiades C, Look AT, Aster JC. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. J Clin Invest. 2014 Feb; 124(2):644-55. View abstract
  22. Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, Harris MH, Silverman LB, Sallan SE, Gutierrez A, Look AT, Qi J, Bradner JE, Kelliher MA. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood. 2014 Feb 13; 123(7):1040-50. View abstract
  23. Zuurbier L, Gutierrez A, Mullighan CG, Canté-Barrett K, Gevaert AO, de Rooi J, Li Y, Smits WK, Buijs-Gladdines JG, Sonneveld E, Look AT, Horstmann M, Pieters R, Meijerink JP. Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors. Haematologica. 2014 Jan; 99(1):94-102. View abstract
  24. Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, Brand M, Gutierrez A, Kelliher MA, Jamieson CH, von Boehmer H, Young RA, Look AT. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29; 210(8):1545-57. View abstract
  25. Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, Yost A, Ma W, Fleischman AG, Zhou W, Yang Y, Kleppe M, Ahn Y, Tatarek J, Kelliher MA, Neuberg DS, Levine RL, Moriggl R, Müller M, Gray NS, Jamieson CH, Weng AP, Staudt LM, Druker BJ, Look AT. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013 May; 3(5):564-77. View abstract
  26. Rao S, Lee SY, Gutierrez A, Perrigoue J, Thapa RJ, Tu Z, Jeffers JR, Rhodes M, Anderson S, Oravecz T, Hunger SP, Timakhov RA, Zhang R, Balachandran S, Zambetti GP, Testa JR, Look AT, Wiest DL. Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood. 2012 Nov 01; 120(18):3764-73. View abstract
  27. Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A, Ma W, Tatarek J, Ahn Y, Kelliher MA, Jamieson CH, Staudt LM, Young RA, Look AT. Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. Cancer Cell. 2012 Aug 14; 22(2):209-21. View abstract
  28. Ma W, Gutierrez A, Goff DJ, Geron I, Sadarangani A, Jamieson CA, Court AC, Shih AY, Jiang Q, Wu CC, Li K, Smith KM, Crews LA, Gibson NW, Deichaite I, Morris SR, Wei P, Carson DA, Look AT, Jamieson CH. NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches. PLoS One. 2012; 7(6):e39725. View abstract
  29. Gutierrez A, Snyder EL, Marino-Enriquez A, Zhang YX, Sioletic S, Kozakewich E, Grebliunaite R, Ou WB, Sicinska E, Raut CP, Demetri GD, Perez-Atayde AR, Wagner AJ, Fletcher JA, Fletcher CD, Look AT. Aberrant AKT activation drives well-differentiated liposarcoma. Proc Natl Acad Sci U S A. 2011 Sep 27; 108(39):16386-91. View abstract
  30. Gutierrez A, Kentsis A, Sanda T, Holmfeldt L, Chen SC, Zhang J, Protopopov A, Chin L, Dahlberg SE, Neuberg DS, Silverman LB, Winter SS, Hunger SP, Sallan SE, Zha S, Alt FW, Downing JR, Mullighan CG, Look AT. The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood. 2011 Oct 13; 118(15):4169-73. View abstract
  31. Gutierrez A, Grebliunaite R, Feng H, Kozakewich E, Zhu S, Guo F, Payne E, Mansour M, Dahlberg SE, Neuberg DS, den Hertog J, Prochownik EV, Testa JR, Harris M, Kanki JP, Look AT. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. J Exp Med. 2011 Aug 01; 208(8):1595-603. View abstract
  32. Rudner LA, Brown KH, Dobrinski KP, Bradley DF, Garcia MI, Smith AC, Downie JM, Meeker ND, Look AT, Downing JR, Gutierrez A, Mullighan CG, Schiffman JD, Lee C, Trede NS, Frazer JK. Shared acquired genomic changes in zebrafish and human T-ALL. Oncogene. 2011 Oct 13; 30(41):4289-96. View abstract
  33. Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS, Zhai B, Wan L, Gutierrez A, Lau AW, Xiao Y, Christie AL, Aster J, Settleman J, Gygi SP, Kung AL, Look T, Nakayama KI, DePinho RA, Wei W. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011 Mar 03; 471(7336):104-9. View abstract
  34. Feng H, Stachura DL, White RM, Gutierrez A, Zhang L, Sanda T, Jette CA, Testa JR, Neuberg DS, Langenau DM, Kutok JL, Zon LI, Traver D, Fleming MD, Kanki JP, Look AT. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010 Oct 19; 18(4):353-66. View abstract
  35. Gutierrez A, Dahlberg SE, Neuberg DS, Zhang J, Grebliunaite R, Sanda T, Protopopov A, Tosello V, Kutok J, Larson RS, Borowitz MJ, Loh ML, Ferrando AA, Winter SS, Mullighan CG, Silverman LB, Chin L, Hunger SP, Sallan SE, Look AT. Absence of biallelic TCRgamma deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia. J Clin Oncol. 2010 Aug 20; 28(24):3816-23. View abstract
  36. Grace RF, Su H, Sena L, Poussaint TY, Heeney MM, Gutierrez A. Resolution of cerebral artery stenosis in a child with sickle cell anemia treated with hydroxyurea. Am J Hematol. 2010 Feb; 85(2):135-7. View abstract
  37. Gutierrez A, Sanda T, Ma W, Zhang J, Grebliunaite R, Dahlberg S, Neuberg D, Protopopov A, Winter SS, Larson RS, Borowitz MJ, Silverman LB, Chin L, Hunger SP, Jamieson C, Sallan SE, Look AT. Inactivation of LEF1 in T-cell acute lymphoblastic leukemia. Blood. 2010 Apr 08; 115(14):2845-51. View abstract
  38. Penning TM, Lee SH, Jin Y, Gutierrez A, Blair IA. Liquid chromatography-mass spectrometry (LC-MS) of steroid hormone metabolites and its applications. J Steroid Biochem Mol Biol. 2010 Aug; 121(3-5):546-55. View abstract
  39. Sanda T, Li X, Gutierrez A, Ahn Y, Neuberg DS, O'Neil J, Strack PR, Winter CG, Winter SS, Larson RS, von Boehmer H, Look AT. Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia. Blood. 2010 Mar 04; 115(9):1735-45. View abstract
  40. Rhodes J, Amsterdam A, Sanda T, Moreau LA, McKenna K, Heinrichs S, Ganem NJ, Ho KW, Neuberg DS, Johnston A, Ahn Y, Kutok JL, Hromas R, Wray J, Lee C, Murphy C, Radtke I, Downing JR, Fleming MD, MacConaill LE, Amatruda JF, Gutierrez A, Galinsky I, Stone RM, Ross EA, Pellman DS, Kanki JP, Look AT. Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Mol Cell Biol. 2009 Nov; 29(21):5911-22. View abstract
  41. Gutierrez A, Sanda T, Grebliunaite R, Carracedo A, Salmena L, Ahn Y, Dahlberg S, Neuberg D, Moreau LA, Winter SS, Larson R, Zhang J, Protopopov A, Chin L, Pandolfi PP, Silverman LB, Hunger SP, Sallan SE, Look AT. High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood. 2009 Jul 16; 114(3):647-50. View abstract
  42. Gutierrez A, Look AT. Cell and molecular biology of human leukaemias. Oxford Textbook of Medicine. 2009. View abstract
  43. Gutierrez A, Look AT. Pathobiology of Acute Lymphoblastic Leukemia. Hematology: Basic Principles and Practice. Editors: Hoffman R et al. 2009. View abstract
  44. O'Neil J, Tchinda J, Gutierrez A, Moreau L, Maser RS, Wong KK, Li W, McKenna K, Liu XS, Feng B, Neuberg D, Silverman L, DeAngelo DJ, Kutok JL, Rothstein R, DePinho RA, Chin L, Lee C, Look AT. Alu elements mediate MYB gene tandem duplication in human T-ALL. J Exp Med. 2007 Dec 24; 204(13):3059-66. View abstract
  45. Gutierrez A, Look AT. NOTCH and PI3K-AKT pathways intertwined. Cancer Cell. 2007 Nov; 12(5):411-3. View abstract
  46. Feng H, Langenau DM, Madge JA, Quinkertz A, Gutierrez A, Neuberg DS, Kanki JP, Look AT. Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. Br J Haematol. 2007 Jul; 138(2):169-75. View abstract
  47. Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A, O'Neil J, Gutierrez A, Ivanova E, Perna I, Lin E, Mani V, Jiang S, McNamara K, Zaghlul S, Edkins S, Stevens C, Brennan C, Martin ES, Wiedemeyer R, Kabbarah O, Nogueira C, Histen G, Aster J, Mansour M, Duke V, Foroni L, Fielding AK, Goldstone AH, Rowe JM, Wang YA, Look AT, Stratton MR, Chin L, Futreal PA, DePinho RA. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature. 2007 Jun 21; 447(7147):966-71. View abstract
  48. Singh G, Gutierrez A, Xu K, Blair IA. Liquid chromatography/electron capture atmospheric pressure chemical ionization/mass spectrometry: analysis of pentafluorobenzyl derivatives of biomolecules and drugs in the attomole range. Anal Chem. 2000 Jul 15; 72(14):3007-13. View abstract