Statut
Thématiques de recherche
In general:
I am a scientist that develops cutting-edge research projects, integrates basic research findings into novel diagnostic and therapeutic approaches and trains competitive scientific staff, as demonstrated by over 60 publications in high profile journals, 2 licensed patents with clinical application, one clinical study and 24 students (5 Postdocs, 12 PhD students, 7 Master students) that graduated from my lab and are pursuing promising scientific careers.
For details see section « Projects » below.
Selected Publications Since 2015:
[65] Swaminathan G, Cordero J, Günther S, Graumann J, Braun T, Dobreva G and Barreto G. Erlotinib induces 3D genome rearrangements in lung cancer cells activating tumor suppressor genes through FOXA2-bound promoters with enhancer activity. BioRxiv; 2025. doi: https://doi.org/10.1101/2025.05.13.653883
[64] Dou Y, Tetik-Elsherbiny N, Gao R, Ren Y, Chen YW, Merbecks M, Setya A, Lityagina O, Wang Y, Chichelnitskiy E, Abouissa A, Wu CC, Barreto G, Potente M, Wieland T, Ola R, Grieshaber P, Loukanov T, Gorenflo M, Heineke J, Cordero J and Dobreva G. Endothelial RNF20 Suppresses Endothelial-to-Mesenchymal Transition and Safeguards Physiological Angiocrine Signaling to Prevent Congenital Heart Disease. Manuscript accepted for publication Nat Commun; 2025 (IF 14.7)
[63] Cabrera-Fuentes HA, Ruiz-Meana M, Barreto G, Serebruany VL, Sánchez-Vega JT, Perez-Campos E, Kostin S, Böning A, González EEJ, Al-Suhaimi EA, Rodriguez-Montesinos J, Inserte J, Pedretti S, Yap J, Irei J, Sedding DG, Lecour S, Liehn EA, Garcia-Dorado D, Hausenloy DJ, Boisvert WA, Preissner KT. Extracellular RNA Drives TNF-α/TNF-Receptor-1 mediated cardiac ischemia/reperfusion injury: Mechanistic insights and therapeutic potential of RNase1. Pharmacol Res; 2025 Sep 12:107944. doi: 10.1016/j.phrs.2025.107944 (IF 10.5)
[59] Liu H, Tang Y, Singh A, Vong J, Cordero J, Mathes A, Gao R, Jia Y, Garvalov BK, Acker T, Poschet G, Hell R, Schneider MA, Heineke J, Wieland T, Barreto G, Cerwenka A, Potente M, Bibli SI, Savai R, Dobreva G. RNF20 links the DNA damage response and metabolic rewiring in lung cancer through HIF1α. Nat Commun; 2025 May 28;16(1):4929. doi: 10.1038/s41467-025-60223-4 (IF 14.7)
[58] Dobersch S, Yamamoto N, Schutter A, Cavender SM, Robertson TM, Kartha N, Samraj AN, Doron B, Poole LA, Wladyka CL, Zhang A, Jang GH, Mahalingam AH, Barreto G, Raghavan S, Narla G, Notta F, Eisenman RN, Hsieh AC, Kugel S. HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity. Nat Commun; 2025 May 26;16(1):4866. doi: 10.1038/s41467-025-60129-1 (IF 14.7)
[56] Cordero J, Swaminathan G, Rogel-Ayala DG, Rubio K, Elsherbiny A, Mahmood S, Szymanski W, Graumann J, Braun T, Günther S, Dobreva G and Barreto G. Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription. Nat Commun; 2024 Dec 20;15(1):10711. doi: 10.1038/s41467-024-54740-x (IF 14.7)
[51] Rubio K, Romero-Olmedo AJ, Pouya S, Swaminathan G, Ranvir VP, Rogel-Ayala DG, Cordero J, Günther S, Metha A, Bassaly B, Braubach P, Wygrecka M, Gattenlöhner S, Tresch A, Braun T, Dobreva G, Rivera MN, Singh I, Graumann J and Barreto G. Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer. Theranostics; 2023; 13(8):2319-2342. doi:10.7150/thno.79493 (IF 12.4)
[38] Dobersch S, Rubio K, Singh I, Günther S, Graumann J, Cordero J, Castillo-Negrete R, Huynh MB, Mehta A, Braubach P, Cabrera-Fuentes H, Bernhagen J, Chao CM, Bellusci S, Günther A, Preissner KT, Dobreva G, Wygrecka M, Braun T, Papy-Garcia D and Barreto G. Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation.
Nat Commun; 2021; Feb 16;12(1):1072. doi: 10.1038/s41467-021-21227-y (IF 17.694)
[37] El-Nikhely N, Karger A, Sarode P, Singh I, Weigert A, Wietelmann A, Stiewe T, Dammann R, Fink L, Grimminger F, Barreto G, Seeger W, Savai Pullamsetti S, Rapp UR and Savai R. Metastasis-associated protein 2 as a repressor of NF-ƙB to reduce lung tumor growth and inflammation. Cancer Res; 2020; Oct 1;80(19):4199-4211. doi: 10.1158/0008-5472.CAN-20-1158 (IF 12.7)
[31] Rubio K, Singh I, Dobersch S, Sarvari P, Günther S, Cordero J, Mehta A, Wujak L, Cabreras-Fuentes H, Chao CH, Bellusci S, Günther A, Dobreva G, Wygrecka M, Seeger W, Preissner KT, Savai R, Papy-Garcia D, Heikenwalder M, Pullamsetti SS, Braun T and Barreto G. Inactivation of nuclear histone deacetylases by EP300 disrupts the MiCEE complex in Idiopathic Pulmonary Fibrosis. Nat Commun; 2019; May 20;10(1):2229. doi: 10.1038/s41467-019-10066-7 (IF 17.694)
[29] Jia Y, Vong JS, Asafova AS, Garvalov BK, Caputo L, Cordero J, Boettger T, Günther S, Fink L, Acker T, Barreto G, Seeger W, Braun T, Savai R and Dobreva G. Lamin B1 loss drives lung cancer development and metastasis by epigenetic derepression of RET proto-oncogene. J Exp Med; 2019; Apr 23. pii: jem.20181394. doi: 10.1084/jem.20181394 (IF 17.579)
[28] Dobersch S, Rubio K and Barreto G. Pioneer factors and architectural proteins mediating embryonic expression signatures in cancer. Trends Mol Med; 2019; Feb 19. pii: S1471-4914(19)30019-X. doi: 10.1016/j.molmed.2019.01.008 (IF 15.272)
[24] Singh I, Contreras A, Cordero J, Rubio K, Dobersch S, Günther S, Jeratsch S, Mehta A, Krüger M, Graumann J, Seeger W, Dobreva G, Braun T and Barreto G. MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolus organization. Nat Genet; 2018; Jul; 50(7):990-1001. doi: 10.1038/s41588-018-0139-3. Epub 2018 Jun 4 (IF 41.379)
[23] Mehta A, Cordero J, Dobersch S, Romero-Olmedo AJ, Savai R, Bodner J, Chao CM, Fink L, Guzmán-Díaz E, Singh I, Dobreva G, Rapp UR, Günther S, Ilinskaya ON, Bellusci S, Dammann RH, Braun T, Seeger W, Gattenlöhner S, Tresch A, Günther A and Barreto G. Non-invasive lung cancer diagnosis by detection of GATA6 and NKX2-1 isoforms in exhaled breath condensate. EMBO Mol Med; 2016; 8, 1380-1389, doi:10.15252/emmm.201606382 (IF 14)
[20] Singh I, Ozturk N, Mehta A, Cordero J, Hasan D, Cosentino C, Sebastian C, Krüger M, Looso M, Carraro G, Bellusci S, Seeger W, Braun T, Mostoslavsky R and Barreto G. High Mobility Group protein mediated transcription requires DNA damage marker γ-H2AX. Cell Research; 2015 Jul;25(7):837-50; doi: 10.1038/cr.2015.67 (IF 46.297)
Responsabilités
Co-Leader of Team GlycoBio
Research group Leader
European and International Correspondent for the IMoPA
Projets
My research activities are centered on the epigenetic mechanisms during embryonic lung development that are recapitulated in several lung diseases, such as lung cancer and lung fibrosis. I work based on the hypothesis that insights on the processes during embryonic development, can be implemented to elucidate the molecular mechanisms responsible for these lung diseases. My work led to landmark papers including seminal studies on:
♦ A novel mechanism of micro RNA (miRNA) induced transcriptional gene silencing based on the interaction of Mirlet7d with long non-coding RNAs (lncRNAs), the RNA exosome complex and the Polycomb Repressive Complex 2 (PRC2) in the cell nucleus (Singh I et al., Nature Genetics, 2018; Rubio K et al., Nature Communications, 2019). So far, the function of miRNAs was primarily seen in the cytoplasm where miRNAs repress gene expression at the posttranscriptional level. Hence, our discovery that Mirlet7d plays a crucial role in the cell nucleus by directing the RNA exosome complex to specific gene loci tagged by the expression of ncRNAs is conceptually novel. I believe that my findings will open a new chapter in the understanding of miRNA biology tying together the function of miRNAs and lncRNAs for gene silencing.
♦ Transcription mediated by the high mobility group proteins requires the DNA damage marker γ-H2AX, thereby supporting that controlled chromatin opening during transcription initiation involve intermediates with DNA breaks that require mechanisms of DNA repair that ensure the integrity of the genome (Singh I et al., Cell Research, 2015; Dobersch S et al., Nature Communications, 2021).
♦ Small cell lung cancer (SCLC) is an extremely aggressive lung cancer type with a patient median survival of 6-12 months. Epidermal growth factor (EGF) signaling plays an important role in triggering SCLC. In addition, growth factor-dependent signals and alpha-, beta-integrin (ITGA, ITGB) heterodimer receptors functionally cooperate and integrate their signaling pathways. However, the precise role of integrins in EGF receptor (EGFR) activation in SCLC has remained elusive. We uncovered a mechanism of non-canonical ITGB2-mediated EGFR activation in SCLC (Rubio K et al., Theranostics, 2023) that explains EGFR-inhibitor resistance independently of EGFR mutations, suggesting the development of therapies targeting ITGB2 for patients with this extremely aggressive lung cancer type.
♦ Our studies place another nuclear miRNA (miR-9) in the same structural and functional context with chromatin features related to increased transcriptional activity, such as H3K4me3 broad domains, G-quadruplexes (G4s) and promoter-super-enhancer looping during 3D genome organization and transcriptional activation induced by tissue growth factor beta 1 (TGFB1) signaling, a critical regulator of proliferation programs in cancer and fibrosis (Cordero J et al., Nature Communications, 2024).
♦ The small molecules erlotinib and gefitinib are FDA-approved EGFR tyrosine kinase inhibitors (TKIs) used to treat non-small cell lung cancer (NSCLC). However, the effects on the genome of LC cells caused by EGFR-TKIs have been sparsely studied. We integrated multi-omics studies (1) showing that EGFR-TKIs induce 3D genome rearrangements in NSCLC cells, (2) linking increased euchromatic H3K4me3 broad domains, reduced heterochromatic H3K27me3 levels, augmented promoter–enhancer looping and FOXA2 binding to promoters with enhancer activity (Epromoters), (3) resulting in transcriptional activation of tumor suppressor genes (TSG). Our manuscript provides further insights into the therapeutic effects of EGFR-TKIs (Swaminathan G et a., 2025 bioRxiv under peer review at Nature Cell Biology).
♦ I also have experience in integrating basic research findings on epigenetic deregulation into the development of diagnostic and therapeutic strategies using molecular targets as demonstrated by two licensed Patents with extensive clinical relevance as they deal with the development of a non-invasive, specific and sensitive method for early lung cancer diagnosis and with a novel approach for lung cancer therapy (Mehta A et al., 2016 EMBO Molecular Medicine, IF 14.26). Currently I am co-leading the clinical study EMoLung with the participation of five different clinical centers in Germany within the context of the German Center for Lung Research (DZL) to confirm the clinical application of our technology.
