Research Topics
Genomes and Genes
| Iannis AifantisSummaryAffiliation: New York University Country: USA Publications
Research Grants
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Detail Information
Publications
Molecular pathogenesis of T-cell leukaemia and lymphomaIannis Aifantis
Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
Nat Rev Immunol 8:380-90. 2008..Finally, we discuss potential new therapies that target oncogenic pathways in T-ALL...
Notches, NFkappaBs and the making of T cell leukemiaIannis Aifantis
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
Cell Cycle 6:403-6. 2007..We believe that these findings could be important for the understanding of Notch1 signaling and the therapeutic treatment of T-ALL...- Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potentialColin H Martin
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute Boston, Massachusetts, 02115, USA
Nat Immunol 4:866-73. 2003..Although the CLP-2 subset may represent the most differentiated population with T cell potential before commitment to the B cell lineage, other subsets of thymic immigrants capable of generating T cells may exist... - A critical role for the cytoplasmic tail of pTalpha in T lymphocyte developmentIannis Aifantis
Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
Nat Immunol 3:483-8. 2002..In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function... 
Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte developmentChristine Borowski
Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
J Exp Med 199:607-15. 2004..We conclude that features intrinsic to the pre-TCR, which are absent in TCRalpha, are essential for its unique function...- Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7Benjamin J Thompson
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
J Exp Med 205:1395-408. 2008.... - ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repressionOmar Abdel-Wahab
Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Cancer Cell 22:180-93. 2012..We demonstrate that ASXL1 associates with the PRC2, and that loss of ASXL1 in vivo collaborates with NRASG12D to promote myeloid leukemogenesis... - Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complexLinsey Reavie
Howard Hughes Medical Institute and Department of Pathology, New York, New York, USA
Nat Immunol 11:207-15. 2010..Our studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentiation... - Hedgehog signaling is dispensable for adult hematopoietic stem cell functionJie Gao
Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
Cell Stem Cell 4:548-58. 2009..quot; Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that Hh inhibition on leukemia-initiating cell maintenance can be targeted in future clinical trials... - Notch pathway activation targets AML-initiating cell homeostasis and differentiationCamille Lobry
Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
J Exp Med 210:301-19. 2013..These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia... - The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemiaBenjamin J Thompson
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
J Exp Med 204:1825-35. 2007..Our data suggest that FBW7 is a novel tumor suppressor in T cell leukemia, and implicate the loss of FBW7 function as a potential mechanism of drug resistance in T-ALL... - Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemiaPedro J Real
Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Nat Med 15:50-8. 2009..These results support a role for glucocorticoids plus GSIs in the treatment of glucocorticoid-resistant T-ALL... - Regulation of hematopoietic stem cell fate by the ubiquitin proteasome systemKelly Moran-Crusio
Department of Pathology and NYU Cancer Institute, NYU School of Medicine, New York, NY 10016, USA
Trends Immunol 33:357-63. 2012..Thus, understanding the emerging field of how the UPS regulates HSC activity may lead to novel targets for therapy of leukemia... - Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter geneFotini Gounari
Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
Nat Immunol 3:489-96. 2002..Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off... - Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanismsErica J Reschly
Department of Pathology, MC1089, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
Blood 107:4115-21. 2006..Our findings indicate that the activation of Notch1 is an important "second hit" for the transformation of E2A(-/-) T cell lymphomas and that Notch1 promotes survival through pre-TCR-dependent and -independent mechanisms... - TET family proteins and their role in stem cell differentiation and transformationLuisa Cimmino
Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
Cell Stem Cell 9:193-204. 2011.... - Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome systemShannon M Buckley
Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Cell Stem Cell 11:783-98. 2012..This global characterization of the UPS as a key regulator of stem cell pluripotency opens the way for future studies that focus on specific UPS enzymes or ubiquitinated substrates... - Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemiaCatherine M Sawai
Department of Pathology and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
Cancer Cell 22:452-65. 2012..These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor... - Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemiaPanagiotis Ntziachristos
Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, New York, USA
Nat Med 18:298-301. 2012..These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation... - Energy addiction and lymphocyte differentiation: a new role for the liver kinase B1 kinaseIannis Aifantis
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, NY 10016, USA
Eur J Immunol 40:19-21. 2010..This study highlights the importance of LKB1 in T-cell development and function, but as discussed in this Commentary, a number of intriguing questions concerning the regulation and additional functions of LKB1 remain... - Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformationKelly Moran-Crusio
Department of Pathology, NYU Cancer Institute, New York University School of Medicine, NY 10016, USA
Cancer Cell 20:11-24. 2011..In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo... - CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemiaSilvia Buonamici
Department of Pathology and New York University Cancer Institute, New York 10016, USA
Nature 459:1000-4. 2009..Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications... - Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centersJulie Chaumeil
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Cell Rep 3:359-70. 2013..Our data identify higher-order loop formation as a key determinant of directed RAG targeting and the maintenance of genome stability... - Fingerprinting acute leukemia: DNA methylation profiling of B-acute lymphoblastic leukemiaLuisa Cimmino
Department of Pathology and Howard Hughes Medical Institute, New York University School of Medicine, New York, New York
Cancer Discov 2:976-8. 2012..Cancer Discov; 2(11); 976-8. ©2012 AACR... - Hijacking T Cell Differentiation: New Insights in TLX Function in T-ALLBryan King
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, NY 10016, USA
Cancer Cell 21:453-5. 2012..In this issue of Cancer Cell, Dadi et al. provide new insights into how these factors are recruited by ETS-1 to the TCRα enhancer and actively repress differentiation... - On the brink of becoming a T cellChristine Borowski
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA
Curr Opin Immunol 14:200-6. 2002..Receptor editing and lineage commitment of alphabeta T cells still represent controversial topics that need further study... - Oncogenic and tumor suppressor functions of Notch in cancer: it's NOTCH what you thinkCamille Lobry
Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY, USA
J Exp Med 208:1931-5. 2011..We discuss the intriguing possibility that the pleiotropic functions of Notch can be tumor suppressive or oncogenic depending on the cellular context... - Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scaleEvgeny Shmelkov
Department of Pharmacology, New York University School of Medicine, New York, NY, USA
Biol Direct 6:15. 2011..Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases... - Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptorIannis Aifantis
University of Chicago, Department of Medicine, Section of Rheumatology, Committees of Immunology, Cancer and Developmental Biology, Chicago, IL 60637, USA
Immunol Rev 209:159-69. 2006..We also connect aberrant pre-TCR signaling to deregulated proliferation and apoptotic balances and thymocyte transformation... - Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymusAbdeljabar El Andaloussi
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA
Nat Immunol 7:418-26. 2006.... - Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stagesPhilipp Oberdoerffer
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Mol Cell Biol 25:3896-905. 2005..The extent of gene inactivation varies between different cell types and is least efficient in mature lymphocytes. Our data suggest that RNAi is affected by factors beyond small interfering RNA-mRNA stoichiometry... - Positive selection by the pre-TCR yields mature CD8+ T cellsYuriko Ito
Center for Immunology, University of Texas Southwestern Medical Center, Dallas 75390, USA
J Immunol 169:4913-9. 2002..The biased production of CD8(+) T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment... - Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signalingKristen Johnson
Department of Molecular Genetics and Cell Biology, University of Chicago, 929 East 57 th Street, GCIS W522, Chicago, IL 60637, USA
Immunity 28:335-45. 2008..We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7-expressing stromal cells... - Thymic selection revisited: how essential is it?Harald von Boehmer
Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
Immunol Rev 191:62-78. 2003..Ectopically expressed organ-specific antigens contribute to thymic self-nonself discrimination, which represents an essential feature for the evolutionary fitness of mammalian species... - Requirement for cyclin D3 in lymphocyte development and T cell leukemiasEwa Sicinska
Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Cancer Cell 4:451-61. 2003..These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies... - The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survivalMalay Mandal
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
J Exp Med 201:603-14. 2005..Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans... - Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemiaTomas Vilimas
Department of Medicine, Section of Rheumatology, University of Chicago, 5841 South Maryland Avenue Chicago, Illinois 60637, USA
Nat Med 13:70-7. 2007..These findings identify NF-kappaB as one of the major mediators of Notch1-induced transformation and suggest that the NF-kappaB pathway is a potential target of future therapies of T-ALL... - The E delta enhancer controls the generation of CD4- CD8- alphabetaTCR-expressing T cells that can give rise to different lineages of alphabeta T cellsIannis Aifantis
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 203:1543-50. 2006..Thus, alphabetaTCR expression by CD4- CD8- thymocytes not only represents a transgenic artifact but occurs under physiological conditions... - A multistep adhesion cascade for lymphoid progenitor cell homing to the thymusM Lucila Scimone
The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:7006-11. 2006..Preferential thymus-tropism of CLP-2 correlated with higher chemokine receptor 9 expression than on other BM progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade... - A unique function for cyclin D3 in early B cell developmentA Byron Cooper
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA
Nat Immunol 7:489-97. 2006..Cyclin D3 has a key function in B cell development by integrating cytokine and pre-B cell receptor-dependent signals to expand the pool of pre-B cells that have successfully rearranged immunoglobulin heavy chain...
Research Grants
- Hedgehog signaling as a novel regulator of hematopoiesisIannis Aifantis; Fiscal Year: 2007..We will complement these experiments with the study of novel Hh activating mouse mutants in which we will define the exact role of the Gli factors in the regulation of mammalian lymphopoiesis and hematopoiesis. ..
- preTCR as an inducer of cell survival and transformationIannis Aifantis; Fiscal Year: 2007..The proposed experiments will help to identify the molecular mechanisms regulating pre-T cell survival and death and pinpoint pre-TCR-induced signaling pathways responsible for the malignant transformation of thymocytes. ..