Fotini Gounari

Research Summary
Fotini Gounari’s laboratory studies how transcription and epigenetic regulators cooperate to guide T cell development. The role of individual regulators is becoming increasingly clear in the development of T cells. However, much less is known on how these regulatory molecules are integrated into complex networks that drive the chromatin conformation and gene expression changes required at each stage of T-cell development. The objectives of the studies are to elucidate how the DNA-binding protein T-cell factor 1 (Tcf-1), coordinates the action of multiple epigenetic and transcription regulators to control gene expression events that instruct T cell differentiation. The long-term goal is to provide a blueprint of the interplay of molecular networks in the development of healthy T-cell immunity and to understand mechanisms underlying immune-related diseases and T cell malignancies.
Biosciences Graduate Program Association
  1. Quandt J, Arnovitz S, Haghi L, Woehlk J, Mohsin A, Okoreeh M, Mathur PS, Emmanuel AO, Osman A, Krishnan M, Morin SB, Pearson AT, Sweis RF, Pekow J, Weber CR, Khazaie K, Gounari F. Wnt-ß-catenin activation epigenetically reprograms Treg cells in inflammatory bowel disease and dysplastic progression. Nat Immunol. 2021 04; 22(4):471-484. View in: PubMed

  2. Gounari F. CRELD1 controls T cell homeostasis. Nat Immunol. 2020 12; 21(12):1480-1482. View in: PubMed

  3. Kong D, Wan Q, Li J, Zuo S, Liu G, Liu Q, Wang C, Bai P, Duan SZ, Zhou B, Gounari F, Lyu A, Lazarus M, Breyer RM, Yu Y. DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells. Circulation. 2020 02 25; 141(8):655-666. View in: PubMed

  4. Saadalla A, Lima MM, Tsai F, Osman A, Singh MP, Linden DR, Dennis KL, Haeryfar SMM, Gurish MF, Gounari F, Khazaie K. Cell Intrinsic Deregulated ß-Catenin Signaling Promotes Expansion of Bone Marrow Derived Connective Tissue Type Mast Cells, Systemic Inflammation, and Colon Cancer. Front Immunol. 2019; 10:2777. View in: PubMed

  5. Mandal M, Okoreeh MK, Kennedy DE, Maienschein-Cline M, Ai J, McLean KC, Kaverina N, Veselits M, Aifantis I, Gounari F, Clark MR. CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis. Nat Immunol. 2019 10; 20(10):1393-1403. View in: PubMed

  6. Yoshida T, Hu Y, Zhang Z, Emmanuel AO, Galani K, Muhire B, Snippert HJ, Williams CJ, Tolstorukov MY, Gounari F, Georgopoulos K. Chromatin restriction by the nucleosome remodeler Mi-2ß and functional interplay with lineage-specific transcription regulators control B-cell differentiation. Genes Dev. 2019 07 01; 33(13-14):763-781. View in: PubMed

  7. Emmanuel AO, Arnovitz S, Haghi L, Mathur PS, Mondal S, Quandt J, Okoreeh MK, Maienschein-Cline M, Khazaie K, Dose M, Gounari F. TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4+CD8+ thymocytes. Nat Immunol. 2018 12; 19(12):1366-1378. View in: PubMed

  8. Saadalla AM, Osman A, Gurish MF, Dennis KL, Blatner NR, Pezeshki A, McNagny KM, Cheroutre H, Gounari F, Khazaie K. Mast cells promote small bowel cancer in a tumor stage-specific and cytokine-dependent manner. Proc Natl Acad Sci U S A. 2018 02 13; 115(7):1588-1592. View in: PubMed

  9. Khan MW, Saadalla A, Ewida AH, Al-Katranji K, Al-Saoudi G, Giaccone ZT, Gounari F, Zhang M, Frank DA, Khazaie K. The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer. Cancer Immunol Immunother. 2018 01; 67(1):13-23. View in: PubMed

  10. Hu Y, Zhang Z, Kashiwagi M, Yoshida T, Joshi I, Jena N, Somasundaram R, Emmanuel AO, Sigvardsson M, Fitamant J, El-Bardeesy N, Gounari F, Van Etten RA, Georgopoulos K. Superenhancer reprogramming drives a B-cell-epithelial transition and high-risk leukemia. Genes Dev. 2016 09 01; 30(17):1971-90. View in: PubMed

  11. Krishnamoorthy V, Carr T, de Pooter RF, Emanuelle AO, Gounari F, Kee BL. Correction: Repression of Ccr9 transcription in mouse T lymphocyte progenitors by the notch signaling pathway. J Immunol. 2015 Jun 15; 194(12):6191. View in: PubMed

  12. Phillips JD, Knab LM, Blatner NR, Haghi L, DeCamp MM, Meyerson SL, Heiferman MJ, Heiferman JR, Gounari F, Bentrem DJ, Khazaie K. Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer. Cancer Immunol Immunother. 2015 Sep; 64(9):1185-91. View in: PubMed

  13. Dennis KL, Saadalla A, Blatner NR, Wang S, Venkateswaran V, Gounari F, Cheroutre H, Weaver CT, Roers A, Egilmez NK, Khazaie K. T-cell Expression of IL10 Is Essential for Tumor Immune Surveillance in the Small Intestine. Cancer Immunol Res. 2015 Jul; 3(7):806-14. View in: PubMed

  14. Krishnamoorthy V, Carr T, de Pooter RF, Emanuelle AO, Akinola EO, Gounari F, Kee BL. Repression of Ccr9 transcription in mouse T lymphocyte progenitors by the Notch signaling pathway. J Immunol. 2015 Apr 01; 194(7):3191-200. View in: PubMed

  15. Jeggo P, Gounari F. Robin Holliday 1932-2014. Nat Struct Mol Biol. 2014 Jun; 21(6):501-2. View in: PubMed

  16. Keerthivasan S, Aghajani K, Dose M, Molinero L, Khan MW, Venkateswaran V, Weber C, Emmanuel AO, Sun T, Bentrem DJ, Mulcahy M, Keshavarzian A, Ramos EM, Blatner N, Khazaie K, Gounari F. ß-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells. Sci Transl Med. 2014 Feb 26; 6(225):225ra28. View in: PubMed

  17. 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. ß-Catenin induces T-cell transformation by promoting genomic instability. Proc Natl Acad Sci U S A. 2014 Jan 07; 111(1):391-6. View in: PubMed

  18. Dennis KL, Blatner NR, Gounari F, Khazaie K. Current status of interleukin-10 and regulatory T-cells in cancer. Curr Opin Oncol. 2013 Nov; 25(6):637-45. View in: PubMed

  19. Gounari F, Kee BL. Fingerprinting ikaros. Nat Immunol. 2013 Oct; 14(10):1034-5. View in: PubMed

  20. 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 Oct 31; 122(18):3149-59. View in: PubMed

  21. Blatner NR, Gounari F, Khazaie K. The two faces of regulatory T cells in cancer. Oncoimmunology. 2013 May 01; 2(5):e23852. View in: PubMed

  22. Li L, Zhang JA, Dose M, Kueh HY, Mosadeghi R, Gounari F, Rothenberg EV. A far downstream enhancer for murine Bcl11b controls its T-cell specific expression. Blood. 2013 Aug 08; 122(6):902-11. View in: PubMed

  23. Blatner NR, Mulcahy MF, Dennis KL, Scholtens D, Bentrem DJ, Phillips JD, Ham S, Sandall BP, Khan MW, Mahvi DM, Halverson AL, Stryker SJ, Boller AM, Singal A, Sneed RK, Sarraj B, Ansari MJ, Oft M, Iwakura Y, Zhou L, Bonertz A, Beckhove P, Gounari F, Khazaie K. Expression of ROR?t marks a pathogenic regulatory T cell subset in human colon cancer. Sci Transl Med. 2012 Dec 12; 4(164):164ra159. View in: PubMed

  24. Aghajani K, Keerthivasan S, Yu Y, Gounari F. Generation of CD4CreER(T²) transgenic mice to study development of peripheral CD4-T-cells. Genesis. 2012 Dec; 50(12):908-13. View in: PubMed

  25. Khazaie K, Zadeh M, Khan MW, Bere P, Gounari F, Dennis K, Blatner NR, Owen JL, Klaenhammer TR, Mohamadzadeh M. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci U S A. 2012 Jun 26; 109(26):10462-7. View in: PubMed

  26. Germar K, Dose M, Konstantinou T, Zhang J, Wang H, Lobry C, Arnett KL, Blacklow SC, Aifantis I, Aster JC, Gounari F. T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci U S A. 2011 Dec 13; 108(50):20060-5. View in: PubMed

  27. Zhang J, Jackson AF, Naito T, Dose M, Seavitt J, Liu F, Heller EJ, Kashiwagi M, Yoshida T, Gounari F, Petrie HT, Georgopoulos K. Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis. Nat Immunol. 2011 Nov 13; 13(1):86-94. View in: PubMed

  28. Dose M, Gounari F. Sleeping beauty: does ETP-ALL awaken later? Blood. 2011 Oct 27; 118(17):4500-1. View in: PubMed

  29. Hu MG, Deshpande A, Schlichting N, Hinds EA, Mao C, Dose M, Hu GF, Van Etten RA, Gounari F, Hinds PW. CDK6 kinase activity is required for thymocyte development. Blood. 2011 Jun 09; 117(23):6120-31. View in: PubMed

  30. Khazaie K, Blatner NR, Khan MW, Gounari F, Gounaris E, Dennis K, Bonertz A, Tsai FN, Strouch MJ, Cheon E, Phillips JD, Beckhove P, Bentrem DJ. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011 Mar; 30(1):45-60. View in: PubMed

  31. Driessens G, Zheng Y, Locke F, Cannon JL, Gounari F, Gajewski TF. Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-?1 phosphorylation. J Immunol. 2011 Jan 15; 186(2):784-90. View in: PubMed

  32. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med. 2010 Nov; 16(11):1321-7. View in: PubMed

  33. Dose M, Gounari F. The My(c)stery of iNKT cell ontogeny. . 2009 Oct 01; 8(19):3082-5. View in: PubMed

  34. Kovalovsky D, Yu Y, Dose M, Emmanouilidou A, Konstantinou T, Germar K, Aghajani K, Guo Z, Mandal M, Gounari F. Beta-catenin/Tcf determines the outcome of thymic selection in response to alphabetaTCR signaling. J Immunol. 2009 Sep 15; 183(6):3873-84. View in: PubMed

  35. Kreslavsky T, Savage AK, Hobbs R, Gounari F, Bronson R, Pereira P, Pandolfi PP, Bendelac A, von Boehmer H. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gammadelta T cells with restricted TCR diversity. Proc Natl Acad Sci U S A. 2009 Jul 28; 106(30):12453-8. View in: PubMed

  36. Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, Beckhove P, Gounari F, Khazaie K. T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 2009 Jul 01; 69(13):5490-7. View in: PubMed

  37. Dose M, Sleckman BP, Han J, Bredemeyer AL, Bendelac A, Gounari F. Intrathymic proliferation wave essential for Valpha14+ natural killer T cell development depends on c-Myc. Proc Natl Acad Sci U S A. 2009 May 26; 106(21):8641-6. View in: PubMed

  38. Hu MG, Deshpande A, Enos M, Mao D, Hinds EA, Hu GF, Chang R, Guo Z, Dose M, Mao C, Tsichlis PN, Gounari F, Hinds PW. A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis. Cancer Res. 2009 Feb 01; 69(3):810-8. View in: PubMed

  39. Li X, Gounari F, Protopopov A, Khazaie K, von Boehmer H. Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1. J Exp Med. 2008 Nov 24; 205(12):2851-61. View in: PubMed

  40. Dose M, Gounari F. Fifty ways to Notch T-ALL. Blood. 2008 Aug 01; 112(3):457-8. View in: PubMed

  41. Gounaris E, Erdman SE, Restaino C, Gurish MF, Friend DS, Gounari F, Lee DM, Zhang G, Glickman JN, Shin K, Rao VP, Poutahidis T, Weissleder R, McNagny KM, Khazaie K. Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci U S A. 2007 Dec 11; 104(50):19977-82. View in: PubMed

  42. Mao C, Tili EG, Dose M, Haks MC, Bear SE, Maroulakou I, Horie K, Gaitanaris GA, Fidanza V, Ludwig T, Wiest DL, Gounari F, Tsichlis PN. Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J Immunol. 2007 May 01; 178(9):5443-53. View in: PubMed

  43. Guo Z, Dose M, Kovalovsky D, Chang R, O'Neil J, Look AT, von Boehmer H, Khazaie K, Gounari F. Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation. Blood. 2007 Jun 15; 109(12):5463-72. View in: PubMed

  44. Dose M, Khan I, Guo Z, Kovalovsky D, Krueger A, von Boehmer H, Khazaie K, Gounari F. c-Myc mediates pre-TCR-induced proliferation but not developmental progression. Blood. 2006 Oct 15; 108(8):2669-77. View in: PubMed

  45. Garbe AI, Krueger A, Gounari F, Zúñiga-Pflücker JC, von Boehmer H. Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate. J Exp Med. 2006 Jun 12; 203(6):1579-90. View in: PubMed

  46. Gounari F, Chang R, Cowan J, Guo Z, Dose M, Gounaris E, Khazaie K. Loss of adenomatous polyposis coli gene function disrupts thymic development. Nat Immunol. 2005 Aug; 6(8):800-9. View in: PubMed

  47. Karagianni N, Ly MC, Psarras S, Chlichlia K, Schirrmacher V, Gounari F, Khazaie K. Novel adenomatous polyposis coli gene promoter is located 40 kb upstream of the initiating methionine. Genomics. 2005 Feb; 85(2):231-7. View in: PubMed

  48. Borowski C, Li X, Aifantis I, Gounari F, von Boehmer H. Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte development. J Exp Med. 2004 Mar 01; 199(5):607-15. View in: PubMed

  49. Martin CH, Aifantis I, Scimone ML, von Andrian UH, Reizis B, von Boehmer H, Gounari F. Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential. Nat Immunol. 2003 Sep; 4(9):866-73. View in: PubMed

  50. von Boehmer H, Aifantis I, Gounari F, Azogui O, Haughn L, Apostolou I, Jaeckel E, Grassi F, Klein L. Thymic selection revisited: how essential is it? Immunol Rev. 2003 Feb; 191:62-78. View in: PubMed

  51. Gounari F, Signoretti S, Bronson R, Klein L, Sellers WR, Kum J, Siermann A, Taketo MM, von Boehmer H, Khazaie K. Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene. 2002 Jun 13; 21(26):4099-107. View in: PubMed

  52. Aifantis I, Borowski C, Gounari F, Lacorazza HD, Nikolich-Zugich J, von Boehmer H. A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development. Nat Immunol. 2002 May; 3(5):483-8. View in: PubMed

  53. Gounari F, Aifantis I, Martin C, Fehling HJ, Hoeflinger S, Leder P, von Boehmer H, Reizis B. Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene. Nat Immunol. 2002 May; 3(5):489-96. View in: PubMed

  54. Borowski C, Martin C, Gounari F, Haughn L, Aifantis I, Grassi F, von Boehmer H. On the brink of becoming a T cell. Curr Opin Immunol. 2002 Apr; 14(2):200-6. View in: PubMed

  55. Miyoshi K, Shillingford JM, Le Provost F, Gounari F, Bronson R, von Boehmer H, Taketo MM, Cardiff RD, Hennighausen L, Khazaie K. Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci U S A. 2002 Jan 08; 99(1):219-24. View in: PubMed

  56. Gounari F, Aifantis I, Khazaie K, Hoeflinger S, Harada N, Taketo MM, von Boehmer H. Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development. Nat Immunol. 2001 Sep; 2(9):863-9. View in: PubMed

  57. Aifantis I, Gounari F, Scorrano L, Borowski C, von Boehmer H. Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappaB and NFAT. Nat Immunol. 2001 May; 2(5):403-9. View in: PubMed

  58. Janosch P, Kieser A, Eulitz M, Lovric J, Sauer G, Reichert M, Gounari F, Büscher D, Baccarini M, Mischak H, Kolch W. The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments. FASEB J. 2000 Oct; 14(13):2008-21. View in: PubMed

  59. Müller M, Gounari F, Prifti S, Hacker HJ, Schirrmacher V, Khazaie K. EblacZ tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells. Cancer Res. 1998 Dec 01; 58(23):5439-46. View in: PubMed

  60. King JA, Bridger JM, Gounari F, Lichter P, Schulz TF, Schirrmacher V, Khazaie K. The extended packaging sequence of MoMLV contains a constitutive mRNA nuclear export function. FEBS Lett. 1998 Sep 04; 434(3):367-71. View in: PubMed

  61. Georgatos SD, Gounari F, Goulielmos G, Aebi U. To bead or not to bead? Lens-specific intermediate filaments revisited. J Cell Sci. 1997 Nov; 110 ( Pt 21):2629-34. View in: PubMed

  62. Gounari F, Karagianni N, Mincheva A, Lichter P, Georgatos SD, Schirrmacher V. The mouse filensin gene: structure and evolutionary relation to other intermediate filament genes. FEBS Lett. 1997 Aug 18; 413(2):371-8. View in: PubMed

  63. Rehberger S, Gounari F, DucDodon M, Chlichlia K, Gazzolo L, Schirrmacher V, Khazaie K. The activation domain of a hormone inducible HTLV-1 Rex protein determines colocalization with the nuclear pore. Exp Cell Res. 1997 Jun 15; 233(2):363-71. View in: PubMed

  64. Goulielmos G, Remington S, Schwesinger F, Georgatos SD, Gounari F. Contributions of the structural domains of filensin in polymer formation and filament distribution. J Cell Sci. 1996 Feb; 109 ( Pt 2):447-56. View in: PubMed

  65. Goulielmos G, Gounari F, Remington S, Müller S, Häner M, Aebi U, Georgatos SD. Filensin and phakinin form a novel type of beaded intermediate filaments and coassemble de novo in cultured cells. J Cell Biol. 1996 Feb; 132(4):643-55. View in: PubMed

  66. Gounari F, Merdes A, Quinlan R, Hess J, FitzGerald PG, Ouzounis CA, Georgatos SD. Bovine filensin possesses primary and secondary structure similarity to intermediate filament proteins. J Cell Biol. 1993 May; 121(4):847-53. View in: PubMed

  67. Georgatos SD, Gounari F, Remington S. The beaded intermediate filaments and their potential functions in eye lens. Bioessays. 1994 Jun; 16(6):413-8. View in: PubMed

  68. Merdes A, Gounari F, Georgatos SD. The 47-kD lens-specific protein phakinin is a tailless intermediate filament protein and an assembly partner of filensin. J Cell Biol. 1993 Dec; 123(6 Pt 1):1507-16. View in: PubMed

  69. Paonessa G, Gounari F, Frank R, Cortese R. Purification of a NF1-like DNA-binding protein from rat liver and cloning of the corresponding cDNA. EMBO J. 1988 Oct; 7(10):3115-23. View in: PubMed

  70. Gounari F, Banks GR, Khazaie K, Jeggo PA, Holliday R. Gene reactivation: a tool for the isolation of mammalian DNA methylation mutants. Genes Dev. 1987 Nov; 1(9):899-912. View in: PubMed

  71. Khazaie K, Gounari F, Antoniou M, deBoer E, Grosveld F. Beta-globin gene promoter generates 5' truncated transcripts in the embryonic/fetal erythroid environment. Nucleic Acids Res. 1986 Sep 25; 14(18):7199-212. View in: PubMed

  72. Ammendola R, Gounari F, Piaggio G, De Simone V, Cortese R. Transcription of the promoter of the rat NF-1 gene depends on the integrity of an Sp1 recognition site. Mol Cell Biol. 1990 Jan; 10(1):387-90. View in: PubMed

  73. Gounari F, De Francesco R, Schmitt J, van der Vliet P, Cortese R, Stunnenberg H. Amino-terminal domain of NF1 binds to DNA as a dimer and activates adenovirus DNA replication. EMBO J. 1990 Feb; 9(2):559-66. View in: PubMed

  74. Abbott C, Piaggio G, Ammendola R, Solomon E, Povey S, Gounari F, De Simone V, Cortese R. Mapping of the gene TCF2 coding for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction. Genomics. 1990 Sep; 8(1):165-7. View in: PubMed