Katia Georgopoulos, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-4445
Fax: (617) 726-4453


katia.georgopoulos@cbrc2.mgh.harvard.edu

Katia Georgopoulos, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Dermatology, Harvard Medical School
  • Associate Biologist, Dermatology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The successful transition of hemopoietic progenitors through the process of lineage commitment and differentiation relies on the precise orchestration of events in gene activation and repression. Our earlier studies on this developmental system have identified the Ikaros family of DNA binding factors. We have shown that these proteins impact the early commitment steps into the hemopoietic and lymphoid lineages and are critical regulators of proliferation in mature T and B cell lymphocytes. We are currently focused on the molecular mechanisms by which these factors effect their function in differentiation. We have recently shown that Ikaros and family members form distinct chromatin remodeling complexes in lymphocytes. The focus of our future research is to delineate the role and regulation of these remodeling complexes in the process of lineage determination and proliferation by a series of biochemical and genetic approaches.

Publications

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  • Georgopoulos K. Ebf1 in DNA repair and leukemogenesis. Blood 2015; 125:3969-71. PubMed
  • Perotti EA, Georgopoulos K, Yoshida T. An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities. PLoS ONE 2015; 10:e0131568. PubMed
  • Yoshida T, Georgopoulos K. Ikaros fingers on lymphocyte differentiation. Int J Hematol 2014; 100:220-9. PubMed
  • Yamada T, Yang Y, Hemberg M, Yoshida T, Cho HY, Murphy JP, Fioravante D, Regehr WG, Gygi SP, Georgopoulos K, Bonni A. Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain. Neuron 2014; 83:122-34. PubMed
  • Joshi I, Yoshida T, Jena N, Qi X, Zhang J, Van Etten RA, Georgopoulos K. Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia. Nat Immunol 2014; 15:294-304. PubMed
  • Dose M, Emmanuel AO, Chaumeil J, Zhang J, Sun T, Germar K, Aghajani K, Davis EM, Keerthivasan S, Bredemeyer AL, Sleckman BP, Rosen ST, Skok JA, Le Beau MM, Georgopoulos K, Gounari F. 硫-Catenin induces T-cell transformation by promoting genomic instability. Proc Natl Acad Sci U S A 2014; 111:391-6. PubMed
  • Yoshida T, Landhuis E, Dose M, Hazan I, Zhang J, Naito T, Jackson AF, Wu J, Perotti EA, Kaufmann C, Gounari F, Morgan BA, Georgopoulos K. Transcriptional regulation of the Ikzf1 locus. Blood 2013; 122:3149-59. PubMed
  • Yoshida T, Georgopoulos K. GATA-3 controls self-renewal in stressed HSCs. Nat Immunol 2013; 14:1032-3. PubMed
  • Quintana FJ, Jin H, Burns EJ, Nadeau M, Yeste A, Kumar D, Rangachari M, Zhu C, Xiao S, Seavitt J, Georgopoulos K, Kuchroo VK. Aiolos promotes TH17 differentiation by directly silencing Il2 expression. Nat Immunol 2012; 13:770-7. PubMed
  • Gómez-del Arco P, Kashiwagi M, Jackson AF, Naito T, Zhang J, Liu F, Kee B, Vooijs M, Radtke F, Redondo JM, Georgopoulos K. Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. Immunity 2010; 33:685-98. PubMed
  • Yoshida T, Ng SY, Georgopoulos K. Awakening lineage potential by Ikaros-mediated transcriptional priming. Curr Opin Immunol 2010; 22:154-60. PubMed
  • Martín-Ibáñez R, Crespo E, Urbán N, Sergent-Tanguy S, Herranz C, Jaumot M, Valiente M, Long JE, Pineda JR, Andreu C, Rubenstein JL, Marín O, Georgopoulos K, Mengod G, Fariñas I, Bachs O, Alberch J, Canals JM. Ikaros-1 couples cell cycle arrest of late striatal precursors with neurogenesis of enkephalinergic neurons. J Comp Neurol 2009; 518:329-51. PubMed
  • Mandal M, Powers SE, Ochiai K, Georgopoulos K, Kee BL, Singh H, Clark MR. Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development. Nat Immunol 2009; 10:1110-7. PubMed
  • Ng SY,Yoshida T,Zhang J,Georgopoulos K. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 2009; 30:493-507. PubMed
  • Georgopoulos K. Acute lymphoblastic leukemia--on the wings of IKAROS. N Engl J Med 2009; 360:524-6. PubMed
  • Georgopoulos K. From immunity to tolerance through HDAC. Nat Immunol 2008; 10:13-4. PubMed
  • Naito T, Gomez-Del Arco P, Williams CJ, Georgopoulos K. Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2beta determine silencer activity and Cd4 gene expression. Immunity 2007; 27:723-34. PubMed
  • Agoston DV, Szemes M, Dobi A, Palkovits M, Georgopoulos K, Gyorgy A, Ring MA. Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation. J Neurochem 2007; 102:1805-16. PubMed
  • Kioussis D, Georgopoulos K. Epigenetic flexibility underlying lineage choices in the adaptive immune system. Science 2007; 317:620-2. PubMed
  • Ng SY, Yoshida T, Georgopoulos K. Ikaros and chromatin regulation in early hematopoiesis. Curr Opin Immunol 2007; 19:116-22. PubMed
  • Kashiwagi M, Morgan BA, Georgopoulos K. The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny. Development 2007; 134:1571-82. PubMed
  • Thompson EC, Cobb BS, Sabbattini P, Meixlsperger S, Parelho V, Liberg D, Taylor B, Dillon N, Georgopoulos K, Jumaa H, Smale ST, Fisher AG, Merkenschlager M. Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits. Immunity 2007; 26:335-44. PubMed
  • Yoshida T, Ng SY, Zuniga-Pflucker JC, Georgopoulos K. Early hematopoietic lineage restrictions directed by Ikaros. Nat Immunol 2006; 7:382-91. PubMed
  • Ueda Y, Okano M, Williams C, Chen T, Georgopoulos K, Li E. Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome. Development 2006; 133:1183-92. PubMed
  • Liu E, Sinha S, Williams C, Cyrille M, Heller E, Snapper SB, Georgopoulos K, St-Arnaud R, Force T, Dedhar S, Gerszten RE. Targeted deletion of integrin-linked kinase reveals a role in T-cell chemotaxis and survival. Mol Cell Biol 2005; 25:11145-55. PubMed
  • Koipally J, Renold A, Kim J, Georgopoulos K. Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes. EMBO J 1999; 18:3090-100. PubMed
  • Georgopoulos K. Gene regulation and cancer. AACR meeting review, the Homestead, Hot Springs, VA, USA, 14-18 October 1998. Biochim Biophys Acta 1999; 1423:R75-9. PubMed
  • Cortes M, Wong E, Koipally J, Georgopoulos K. Control of lymphocyte development by the Ikaros gene family. Curr Opin Immunol 1999; 11:167-71. PubMed
  • Avitahl N, Winandy S, Friedrich C, Jones B, Ge Y, Georgopoulos K. Ikaros sets thresholds for T cell activation and regulates chromosome propagation. Immunity 1999; 10:333-43. PubMed
  • Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 1999; 10:345-55. PubMed
  • Wang JH, Avitahl N, Cariappa A, Friedrich C, Ikeda T, Renold A, Andrikopoulos K, Liang L, Pillai S, Morgan BA, Georgopoulos K. Aiolos regulates B cell activation and maturation to effector state. Immunity 1998; 9:543-53. PubMed
  • Kelley CM, Ikeda T, Koipally J, Avitahl N, Wu L, Georgopoulos K, Morgan BA. Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Curr Biol 1998; 8:508-15. PubMed
  • Nichogiannopoulou A, Trevisan M, Friedrich C, Georgopoulos K. Ikaros in hemopoietic lineage determination and homeostasis. Semin Immunol 1998; 10:119-25. PubMed
  • Wu L, Nichogiannopoulou A, Shortman K, Georgopoulos K. Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity 1997; 7:483-92. PubMed
  • Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, Wu P, Neben S, Georgopoulos K. Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation. EMBO J 1997; 16:2004-13. PubMed
  • Georgopoulos K. Transcription factors required for lymphoid lineage commitment. Curr Opin Immunol 1997; 9:222-7. PubMed
  • Georgopoulos K, Winandy S, Avitahl N. The role of the Ikaros gene in lymphocyte development and homeostasis. Annu Rev Immunol 1997; 15:155-76. PubMed
  • Wang JH, Nichogiannopoulou A, Wu L, Sun L, Sharpe AH, Bigby M, Georgopoulos K. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 1996; 5:537-49. PubMed
  • Sun L, Liu A, Georgopoulos K. Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. EMBO J 1996; 15:5358-69. PubMed
  • Moln. The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse. J Immunol 1996; 156:585-92. PubMed
  • Winandy S, Wu P, Georgopoulos K. A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. Cell 1995; 83:289-99. PubMed
  • Clevers HC, Oosterwegel MA, Georgopoulos K. Transcription factors in early T-cell development. Immunol Today 1993; 14:591-6. PubMed
  • Georgopoulos K, Moore DD, Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science 1992; 258:808-12. PubMed
  • Georgopoulos K, Morgan BA, Moore DD. Functionally distinct isoforms of the CRE-BP DNA-binding protein mediate activity of a T-cell-specific enhancer. Mol Cell Biol 1992; 12:747-57. PubMed
  • Oosterwegel M, van de Wetering M, Dooijes D, Klomp L, Winoto A, Georgopoulos K, Meijlink F, Clevers H. Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers. J Exp Med 1991; 173:1133-42. PubMed
  • Georgopoulos K, Galson D, Terhorst C. Tissue-specific nuclear factors mediate expression of the CD3 delta gene during T cell development. EMBO J 1990; 9:109-15. PubMed
  • Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988; 55:917-24. PubMed
  • Georgopoulos K, van den Elsen P, Bier E, Maxam A, Terhorst C. A T cell-specific enhancer is located in a DNase I-hypersensitive area at the 3' end of the CD3-delta gene. EMBO J 1988; 7:2401-7. PubMed
  • Saito H, Koyama T, Georgopoulos K, Clevers H, Haser WG, LeBien T, Tonegawa S, Terhorst C. Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements. Proc Natl Acad Sci U S A 1987; 84:9131-4. PubMed
  • van den Elsen P, Georgopoulos K, Shepley BA, Orkin S, Terhorst C. Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex. Proc Natl Acad Sci U S A 1986; 83:2944-8. PubMed
  • Terhorst C, de Vries J, Georgopoulos K, Gold D, Oettgen H, Pettey C, Spits H, Ucker D, van den Elsen P, Wileman T. The T cell receptor/T3 complex. Year Immunol 1985; 2:245-53. PubMed
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