Lab Publications (2012-Today)

A membrane-associated MHC-I inhibitory axis for cancer immune evasion

Chen X, Lu Q, Zhou H, Liu J, Nadorp B, Lasry A, Sun Z, Lai B, Rona G, Zhang J, Cammer M, Wang K, Al-Santli W, Ciantra Z, Guo Q, You J, Sengupta D, Boukhris A, Zhang H, Liu C, Cresswell P, Dahia PLM, Pagano M, Aifantis I*, Wang J*. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell. 2023 Aug 31;186(18):3903-3920.e21. PMID: 37557169.

Valine tRNA levels and availability regulate complex I assembly in leukaemia

Palaniraja Thandapani, Andreas Kloetgen, Matthew T. Witkowski, Christina Glytsou, Anna K. Lee, Eric Wang, Jingjing Wang, Sarah E. LeBoeuf, Kleopatra Avrampou, Thales Papagiannakopoulos, Aristotelis Tsirigos & Iannis Aifantis. Nature. 2022. VOLUME 601, ISSUE 7893, January 20th, 2022

Surface antigen-guided CRISPR screens identify regulators of myeloid leukemia differentiation

Eric Wang, Hua Zhou, Bettina Nadorp, Geraldine Cayanan, Xufeng Chen, Anna H. Yeaton, Sofia Nomikou, Matthew T. Witkowski, Sonali Narang, Andreas Kloetgen, Palaniraja Thandapani, Niklas Ravn-Boess, Aristotelis Tsirigos, Iannis Aifantis. Cell Press. 2021. VOLUME 28, ISSUE 4, P718-731.E6, APRIL 01, 2021

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

Witkowski MT*, Dolgalev I*, Evensen NA, et al. Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia [published online ahead of print, 2020 May 14]. Cancer Cell. 2020;S1535-6108(20)30214-2. doi:10.1016/j.ccell.2020.04.015

*Equal contribution

Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia

Kloetgen A*, Thandapani P*, Ntziachristos P*, Ghebrechristos Y, Nomikou S, Lazaris C, Chen X, Hu H, Bakogianni S, Wang J, Fu Y, Boccalatte F, Zhong H, Paietta E, Trimarchi T, Zhu Y, Van Vlierberghe P, Inghirami GG, Lionnet T, Aifantis I, Tsirigos A. Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia. Nat Genet. 2020 Apr;52(4):388-400. doi: 10.1038/s41588-020-0602-9. Epub 2020 Mar 23. PubMed PMID: 32203470; PubMed Central PMCID: PMC7138649.

*Equal contribution

On Epigenetic Plasticity and Genome Topology

Lazaris C, Aifantis I, Tsirigos A. On Epigenetic Plasticity and Genome Topology. Trends Cancer. 2020 Mar;6(3):177-180. doi: 10.1016/j.trecan.2020.01.006. Epub 2020 Feb 7. PubMed PMID: 32101721.

Mapping and targeting of the leukemic microenvironment

Witkowski MT, Kousteni S, Aifantis I. Mapping and targeting of the leukemic microenvironment. J Exp Med. 2020 Feb 3;217(2). pii: e20190589. doi:
10.1084/jem.20190589. PubMed PMID: 31873722; PubMed Central PMCID: PMC7041707.

Immune-Based Therapies in Acute Leukemia

Witkowski MT, Lasry A, Carroll WL, Aifantis I. Immune-Based Therapies in Acute Leukemia. Trends Cancer. 2019 Oct;5(10):604-618. doi: 10.1016/j.trecan.2019.07.009. Epub 2019 Aug 29. Review. PubMed PMID: 31706508; PubMed Central PMCID: PMC6859901.

3D Chromosomal Landscapes in Hematopoiesis and Immunity

Kloetgen A*, Thandapani P*, Tsirigos A, Aifantis I. 3D Chromosomal Landscapes in Hematopoiesis and Immunity. Trends Immunol. 2019 Sep;40(9):809-824. doi:10.1016/j.it.2019.07.003. Epub 2019 Aug 15. Review. PubMed PMID: 31422902; PubMed Central PMCID: PMC6718347.

*Equal contribution

Targeting mitochondrial structure sensitizes acute myeloid leukemia to Venetoclax treatment

Chen X*, Glytsou C*, Zhou H, Narang S, Reyna DE, Lopez A, Sakellaropoulos T, Gong Y, Kloetgen A, Yap YS, Wang E, Gavathiotis E, Tsirigos A, Tibes R, Aifantis I.Targeting mitochondrial structure sensitizes acute myeloid leukemia to Venetoclax treatment. Cancer Discovery. 2019 May 2.

*Equal contribution

The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation

Guillamot M, Ouazia D, Dolgalev I, Yeung ST, Kourtis N, Dai Y, Corrigan K, Zea-Redondo L, Saraf A, Florens L, Washburn MP, Tikhonova AN, Malumbres M, Gong Y, Tsirigos A, Park C, Barbieri C, Khanna KM, Busino L, Aifantis I. The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation. Nat Immunol. 2019 Sep;20(9):1196-1207. doi: 10.1038/s41590-019-0454-6. Epub 2019 Aug 12. PubMed PMID: 31406379.

The bone marrow microenvironment at single-cell resolution

Tikhonova AN*, Dolgalev I*, Hu H, Sivaraj KK, Hoxha E, Cuesta-Domínguez Á, Pinho S, Akhmetzyanova I, Gao J, Witkowski M, Guillamot M, Gutkin MC, Zhang Y, Marier C, Diefenbach C, Kousteni S, Heguy A, Zhong H, Fooksman DR, Butler JM, Economides A, Frenette PS, Adams RH, Satija R, Tsirigos A, Aifantis I.The bone marrow microenvironment at single-cell resolution.Nature. 2019 Apr 10. doi: 10.1038/s41586-019-1104-8.

*Equal contribution

Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia

Wang E*, Lu SX*, Pastore A*, Chen X, Imig J, Chun-Wei Lee S, Hockemeyer K, Ghebrechristos YE, Yoshimi A, Inoue D, Ki M, Cho H, Bitner L, Kloetgen A, Lin KT, Uehara T, Owa T, Tibes R, Krainer AR, Abdel-Wahab O, Aifantis I.Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia.Cancer Cell. 2019 Mar 18;35(3):369-384.e7.

*Equal contribution

Cancer Cell Issue Highlight Article (click here)

Oncogenic hijacking of the stress response machinery in T cell acute lymphoblastic leukemia

Nikos Kourtis*, Charalampos Lazaris*, Kathryn Hockemeyer, Juan Carlos Balandrán, Alejandra R. Jimenez, Jasper Mullenders, Yixiao Gong, Thomas Trimarchi, Kamala Bhatt, Hai Hu, Liza Shrestha, Alberto Ambesi-Impiombato, Michelle Kelliher, Elisabeth Paietta, Gabriela Chiosis, Monica L. Guzman, Adolfo A. Ferrando, Aristotelis Tsirigos & Iannis Aifantis. Oncogenic hijacking of the stress response machinery in T cell acute lymphoblastic leukemia. Nature Medicine 2018 Jul 23. DOI: 10.1038/s41591-018-0105-8

*Equal contribution

Vitamin C in Stem Cell Reprogramming and Cancer

Luisa Cimmino, Benjamin G. Neel, Iannis Aifantis

(In Press, Trends in Cell Biology, available online April 30th 2018).

Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries

Yixiao Gong*, Charalampos Lazaris*, Theodore Sakellaropoulos, Aurelie Lozano, Prabhanjan Kambadur, Panagiotis Ntziachristos, Iannis Aifantis & Aristotelis Tsirigos. Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries. Nature Communications 9 (542). DOI:10.1038/s41467-018-03017-1 (published online February 7th 2018).

*Equal contribution

Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression

Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Martín MT, Guillamot M, Banh RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I. Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression. Cell. 2017 Aug 16 DOI: 10.1016/j.cell.2017.07.032, PMID: 28823558

Opposing Functions of H2BK120 Ubiquitylation and H3K79 Methylation in the Regulation of Pluripotency by the Paf1 Complex

Alexandros Strikoudis, Charalampos Lazaris, Panagiotis Ntziachristos, Aristotelis Tsirigos and Iannis Aifantis. Opposing functions of H2BK120 ubiquitylation and H3K79 methylation in the regulation of pluripotency by the Paf1 complex. Cell Cycle 2017, 10.1080/15384101.2017.1295194.

HiC-bench: comprehensive and reproducible Hi-C data analysis designed for parameter exploration and benchmarking

Charalampos Lazaris, Stephen Kelly, Panagiotis Ntziachristos, Iannis Aifantis & Aristotelis Tsirigos. HiC-bench: comprehensive and reproducible Hi-C data analysis designed for parameter exploration and benchmarking. BMC Genomics 2017 18:22. doi: 10.1186/s12864-016-3387-6

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis

Beatriz Aranda-Orgilles, Ricardo Saldaña-Meyer, Eric Wang, Eirini Trompouki, Anne Fassl, Stephanie Lau, Jasper Mullenders, Pedro P. Rocha, Ramya Raviram, María Guillamot, María Sánchez-Díaz, Kun Wang, Clarisse Kayembe, Nan Zhang, Leonela Amoasii, Avik Choudhuri, Jane A. Skok, Markus Schober, Danny Reinberg, Piotr Sicinski, Heinrich Schrewe, et al.
Cell Stem Cell, Volume 19, Issue 6, 1 December 2016, Pages 784-799

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a.

Alexandros Strikoudis, Charalampos Lazaris, Thomas Trimarchi, Antonio L. Galvao Neto, Yan Yang, Panagiotis Ntziachristos, Scott Rothbart, Shannon Buckley, Igor Dolgalev, Matthias Stadtfeld, Brian D. Strahl, Brian D. Dynlacht, Aristotelis Tsirigos & Iannis Aifantis. Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. Nature Cell Biology 18, 1127–1138 (2016) doi:10.1038/ncb3424.

The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.

Bryan King, Francesco Boccalatte, Kelly Moran-Crusio, Elmar Wolf, Jingjing Wang, Clarisse Kayembe, Charalampos Lazaris, Xiaofeng Yu, Beatriz Aranda-Orgilles, Anna Lasorella & Iannis Aifantis. The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells. Nature Immunology 17, 1312–1321 (2016) doi:10.1038/ni.3559.

Emerging Concepts of Epigenetic Dysregulation in Hematological Malignancies.

Ntziachristos P, Abdel-Wahab O, Aifantis I.: Emerging concepts of epigenetic dysregulation in hematological malignancies. Nature Immunology 2016, 01 August.

The Impact of DNA Methylation in Hematopoietic Malignancies.

Guillamot M, Cimmino L, Aifantis I: The Impact of DNA Methylation in Hematopoietic Malignancies. Trends in Cancer 2016, 2:70–83.

Emerging roles for the FBXW7 ubiquitin ligase in leukemia and beyond.

N. Kourtis, A. Strikoudis, and I. Aifantis, “Emerging roles for the FBXW7 ubiquitin ligase in leukemia and beyond,”
Current Opinion in Cell Biology, vol. 37, pp. 28–34, Dec. 2015.

The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis.

Gao J, Buckley SM, Cimmino L, Guillamot M, Strikoudis A, Cang Y, Goff SP, Aifantis I. The CUL4-DDB1 ubiquitin ligase complex controls adult and embryonic stem cell differentiation and homeostasis.
Elife. 2015 Nov 27;4. pii: e07539. doi: 10.7554/eLife.07539. PMID: 26613412

Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms.

Jasper Mullenders, Beatriz Aranda-Orgilles, Priscillia Lhoumaud, Matthew Keller, Juhee Pae, Kun Wang, Clarisse Kayembe, Pedro P. Rocha, Ramya Raviram, Yixiao Gong, Prem K. Premsrirut, Aristotelis Tsirigos, Richard Bonneau, Jane A. Skok, Luisa Cimmino, Daniela Hoehn and Iannis Aifantis. Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms.
JEM 212(11):1833-1850, doi: 10.1084/jem.20151323.

CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance.

Pitt LA, Tikhonova AN, Hu H, Trimarchi T, King B, Gong Y, Sanchez-Martin M, Tsirigos A, Littman DR, Ferrando AA, Morrison SJ, Fooksman DR, Aifantis I, Schwab SR. CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance.
Cancer Cell. 2015 Jun 8;27(6):755-68. doi: 10.1016/j.ccell.2015.05.002. PubMed PMID: 26058075.

TET1 is a tumor suppressor of hematopoietic malignancy

Cimmino L, Dawlaty MM, Ndiaye-Lobry D, Yap YS, Bakogianni S, Yu Y, Bhattacharyya S, Shaknovich R, Geng H, Lobry C, Mullenders J, King B, Trimarchi T, Aranda-Orgilles B, Liu C, Shen S, Verma AK, Jaenisch R, Aifantis I. TET1 is a tumor suppressor of hematopoietic malignancy. Nat Immunol. 2015 Jun;16(6):653-62. doi: 10.1038/ni.3148. Epub 2015 Apr 13.
PubMed PMID: 25867473.

FBXW7 modulates cellular stress response and metastatic potential through HSF1 post-translational modification.

Nikos Kourtis, Rana S. Moubarak, Beatriz Aranda-Orgilles, Kevin Lui, Iraz T. Aydin, Thomas Trimarchi, Farbod Darvishian, Christine Salvaggio, Judy Zhong, Kamala Bhatt, Emily I. Chen, Julide T. Celebi, Charalampos Lazaris, Aristotelis Tsirigos, Iman Osman, Eva Hernando & Iannis Aifantis

Nature Cell Biology 17, 322–332 (2015) | doi:10.1038/ncb3121

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia.

Panagiotis Ntziachristos, Aristotelis Tsirigos, G. Grant Welstead, Thomas Trimarchi, Sofia Bakogianni, Luyao Xu, Evangelia Loizou, Linda Holmfeldt, Alexandros Strikoudis, Bryan King, Jasper Mullenders, Jared Becksfort, Jelena Nedjic, Elisabeth Paietta, Martin S. Tallman, Jacob M. Rowe, Giovanni Tonon, Takashi Satoh, Laurens Kruidenier, Rab Prinjha, Shizuo Akira, Pieter Van Vlierberghe, Adolfo A. Ferrando, Rudolf Jaenisch, Charles G. Mullighan & Iannis Aifantis.
Nature. 2014 Aug 17

Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia.

Trimarchi T, Bilal E, Ntziachristos P, Fabbri G, Dalla-Favera R, Tsirigos A, Aifantis I.
Cell. 2014 Jul 31

Regulation of stem cell function by protein ubiquitylation.

Strikoudis A, Guillamot M, Aifantis I.
EMBO Rep. 2014

From fly wings to targeted cancer therapies: a centennial for notch signaling.

Ntziachristos P, Lim JS, Sage J, Aifantis I.
Cancer Cell. 2014 Mar 17

Notch signaling: switching an oncogene to a tumor suppressor.

Lobry C, Oh P, Mansour MR, Look AT, Aifantis I.
Blood. 2014 Apr 17

Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo.

Abdel-Wahab O, Gao J, Adli M, Dey A, Trimarchi T, Chung YR, Kuscu C, Hricik T, Ndiaye-Lobry D, Lafave LM, Koche R, Shih AH, Guryanova OA, Kim E, Li S, Pandey S, Shin JY, Telis L, Liu J, Bhatt PK, Monette S, Zhao X, Mason CE, Park CY, Bernstein BE, Aifantis I, Levine RL.

J Exp Med. 2013 Nov 18

The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage.

Chaumeil J, Micsinai M, Ntziachristos P, Roth DB, Aifantis I, Kluger Y, Deriano L, Skok JA.

Nat Commun. 2013

A new player SETs in myeloid malignancy.

Trimarchi T, Ntziachristos P, Aifantis I.

Nat Genet. 2013 Aug

The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.

King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, Aranda-Orgilles B, Perez-Garcia A, Shi J, Vakoc C, Sandy P, Shen SS, Ferrando A, Aifantis I.

Cell. 2013 Jun 20

In vivo mapping of notch pathway activity in normal and stress hematopoiesis.

Oh P, Lobry C, Gao J, Tikhonova A, Loizou E, Manent J, van Handel B, Ibrahim S, Greve J, Mikkola H, Artavanis-Tsakonas S, Aifantis I.

Cell Stem Cell. 2013 Aug 1

Mechanisms of epigenetic regulation of leukemia onset and progression.

Ntziachristos P, Mullenders J, Trimarchi T, Aifantis I.

Adv Immunol. 2013

Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression.

Reavie L, Buckley SM, Loizou E, Takeishi S, Aranda-Orgilles B, Ndiaye-Lobry D, Abdel-Wahab O, Ibrahim S, Nakayama KI, Aifantis I.

Cancer Cell. 2013 Mar 18

Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centers.

Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang JM, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA.

Cell Rep. 2013 Feb 21

Distinct TCR signaling pathways drive proliferation and cytokine production in T cells.

Guy CS, Vignali KM, Temirov J, Bettini ML, Overacre AE, Smeltzer M, Zhang H, Huppa JB, Tsai YH, Lobry C, Xie J, Dempsey PJ, Crawford HC, Aifantis I, Davis MM, Vignali DA.

Nat Immunol. 2013 Mar

Notch pathway activation targets AML-initiating cell homeostasis and differentiation.

Lobry C, Ntziachristos P, Ndiaye-Lobry D, Oh P, Cimmino L, Zhu N, Araldi E, Hu W, Freund J, Abdel-Wahab O, Ibrahim S, Skokos D, Armstrong SA, Levine RL, Park CY, Aifantis I.

J Exp Med. 2013 Feb 11

Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system.

Buckley SM, Aranda-Orgilles B, Strikoudis A, Apostolou E, Loizou E, Moran-Crusio K, Farnsworth CL, Koller AA, Dasgupta R, Silva JC, Stadtfeld M, Hochedlinger K, Chen EI, Aifantis I.

Cell Stem Cell. 2012 Dec 7

The taming of the NF-κB: PP4R1 navigates while PP4c dephosphorylates.

Tikhonova A, Aifantis I.

Immunity. 2012 Oct 19