The Laboratory of Molecular Mechanisms in Blood Diseases_en

Principal Investigator: RNDr. Karina Savvulidi Vargova, Ph.D.

Email: vargova.mmbd@gmail.com; karin.vargova@lf.cuni.cz

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Lab Members:

Ph.D. student: MSc. Elena Golovina

Ph.D. thesis: CRISPR/Cas9 as a new tool for the study of oncogenic microRNAs networks in chronic lymphocytic leukemia (CLL).

Grant support: START/MED/089 (2021-2023) ("Influence of miR-155 deficiency on the cell cycle dynamics in normoxia vs hypoxia conditions").

Email: golovinaelena38@gmail.com, elena.golovina@lf1.cuni.cz

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Medical students (First Faculty of Medicine, Charles University): working on the circRNA project

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Virginia Cox, Email: virginia.cox6@gmail.com


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Cory Eaton, Email: cdjeaton@gmail.com


Lab at a glance:

Our research activity is focused on the understanding of molecular mechanisms in human B-cell leukemias (CLL, DLBCL) in relation to the non-coding RNAs as miRNAs, circRNAs.

Current aims:

Elicit how the deletion of oncogenic miRNA - miR-155 in CLL cells affects: cell proliferation, cell cycle dynamics under normoxia vs hypoxia conditions. To describe changes at the level of transcriptome, miRnome and metabolom in miR-155 deficient CLL cell lines (MEC-1, HG-3 cell lines).

 

Evaluation of the expression level of circRNA in DLBCL in association with diseases progression and response to the therapy.

Methods: CRISPR/Cas9 technology), Gene Expression Analysis (mRNA, miRNA, circRNA), Sequencing (mRNA, miRNA), Proteomics, Coy hypoxic glove box and other advanced techniques (cell sorting by FACS, Image cytometry, Fluorescence microscopy).

Funding: PRIMUS/17/MED/16 (2018-2022)

Collaborations - CZ:

  • Biocev, Laboratory of Laboratory of Haematooncology and Stem Cells, Vestec, First Faculty of Medicine, Charles University, Prague (Prof. Tomas Stopka, MD, Ph.D.)
  • Institute of Pathological Physiology, Lymphoma Lab, First Faculty of Medicine, Charles University, Prague (Prof. Pavel Klener, MD, Ph.D.)
  • General University Hospital in Prague (Prof. Marek Trněny, MD, Ph.D.)
  • Center for Advanced Preclinical Imaging, First Faculty of Medicine, Charles University, Prague (RNDr. Ludek Sefc, CSc.)
  • Center of the Region Hana for Biotechnological and Agricultural Research, Faculty of Science, Palacky University, Olomouc (Prof. Marek Sebela, Ph.D.)
  • Department of Animal Sciences, Faculty of Agrobiology, Food, and Natural Resources, Czech University of Life Sciences Prague (ČZU) (Ing., Filipp Georgijevič Savvulidi, Ph.D.)

Collaborations - Interational:

  • Centre National de Recherche en Génomique Humaine (CNRGH), CEA - Institut de Biologie Francois Jacob, Universite Paris - Saclay, Évry, France (Jorg Tost, Ph.D.)

  • Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan (MSc., Oxana Yurikova, Ph.D.)

  • Oncological Pharmacology Laboratory, Department of Oncology, University of Torino, Italy (Prof. Chiara Riganti, MD, Ph.D.)

  • Department of Molecular Biotechnology and Health Sciences, University of Torino and Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy (Prof. Marta Coscia, MD, Ph.D.)

  • Department of Animal Breeding and Agriculture Advisory, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Poland (Asst. prof. Monika Gregula-Kania, Ph.D.)

Publications since 2017:

Elena Golovina, Tomas Heizer, Lenka Daumova, Martin Bajecny, Simona Fontana, Valentina Griggio, Rebecca Jones, Marta Coscia, Chiara Riganti, Karina Savvulidi Vargova. MiR-155 deficiency and hypoxia result in a metabolism switch in the leukemic B-cells. Cancer Cell International. 2024. (IF=6.4)


Filipp Georgijevič Savvulidi, Martin Ptáček, Anežka Málková, Elena Golovina, Jan Pytlík, Martina Janošíková, Szabolcs Nagy, João Pedro Barbas, Luděk Stádník and Karina Savvulidi Vargová. A pilot study on the uptake of propidium iodide and YO-PRO-1 iodide through the pannexin channels in Wallachian frozen-thawed ram spermatozoa. Folia Biologica. 2023. 69, 127-132. (IF=1.1)


Minařík L, Pimková K, Kokavec J, Schaffartziková A, Vellieux F, Kulvait V, Daumová L, Dusilková N, Jonášová A, Vargová KS, Králová Viziová P, Sedláček R, Zemanová Z, Stopka T. Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways. Cells. 2022.11(2):223. doi.org/10.3390/cells11020223. (IF=6.6)


Savvulidi F, Ptacek M, Savvulidi Vargova K, Stadnik L. Manipulation of spermatogonial stem cells in livestock species. J Anim Sci Biotechnol. 2019. Jun 12;10:46. doi: 10.1186/s40104-019-0355-4. eCollection 2019. (IF=3.4)


Polgarova K, Vargova K, Kulvait V, Dusilkova N, Minarik L, Zemanova Z, Pesta M, Jonasova A and Stopka T. Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selectin in patients-responders. Oncotarget. 2017. Dec 6. (IF=5.168)

 

Huskova H, Ardin M, Weninger A, Vargova K, Barrin S, Villar S, Olivier M, Stopka T, Herceg Z, Hollstein M, Zavadil J, Korenjak M. Modeling cancer driver events in vitro using barrier bypass-clonal expansion assays and massively parallel sequencing. Oncogene. 2017. Oct 26;36(43):6041-6048. doi: 10.1038/onc.2017.215. Epub 2017 Jul 10. (IF=6.9)


K.Vargova, Pesta M, Obrtlíkova P, Dusilkova N, Minarik L, Vargova J, Berkova A, Zemanova Z, Michalova K, Spacek M, Trneny M, Stopka T. MiR-155/miR-150 Network Regulates Progression through the Disease Phases of Chronic Lymphocytic Leukemia. Blood Cancer J. 2017. Jul 21;7(7):e585. doi: 10.1038/bcj.2017.63. (IF=4.5)


J.Vargova, K. Vargova, N.Dusilkova, V.Kulvait, V.Pospisil, J.Zavadil, M.Trneny, P.Klener and T. Stopka. Differential expression, localization and activity of MARCKS between mantle cell lymphoma and chronic lymphocytic leukemia. Blood Cancer J. 2016. Sep 23;6(9):e475. doi: 10.1038/bcj.2016.80. (IF=4.5)


Hana Huskova, Katarina Korecka, Josef Karban, Jarmila Vargova, Karina Vargova, Nina Dusilkova, Marek Trneny and Tomas Stopka. Oncogenic microRNA-155 and its target PU.1: an integrative gene expression study in six of the most prevalent lymphomas. IJHM. 2015. Oct;102(4):441-50. doi: 10.1007/s12185-015-1847-4. Epub 2015 Aug 11. (IF=1.8)


Petra Basova, Vit Pospisil, Filipp Savvulidi, Pavel Burda, Karina Vargova, Libor Stanek, Martina Dluhosova, Erika Kuzmova, Anna Jonasova, Ulrich Steidl, Peter Laslo and Tomas Stopka. Aggressive acute myeloid leukemia in PU.1/p53 double-mutant mice. Oncogene. 2014. Sept 25, 4735-45. (IF=7.4)


N Curik, P Burda, K Vargova, V Pospisil, M Belickova, P Vlckova, F Savvulidi, E Necas, H Hajkova, C Haskovec, J Cermak, M Krivjanska, M Trneny, P Laslo, A Jonasova and T Stopka. 5-Azacitidine in aggressive myelodisplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity. Leukemia, 2012. Aug;26(8):1804-11. doi: 10.1038/leu.2012.47. Epub 2012 Feb 20. (IF=9.5)


Pospisil V, Vargova K, Kokavec J, Rybarova J, Savvulidi F, Jonasova A, Necas E, Zavadil J, Laslo P, and Stopka T. Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation. EMBO J. 2011. Sep 6;30(21):4450-64. doi: 10.1038/emboj.2011.317. (IF=10.2)


Vargova K, Curik N, Burda P, Basova P, Kulvait V, Pospisil V, Savvulidi F, Kokavec J, Necas E, Berkova A, Obrtlikova P, Karban J, Mraz M, Pospisilova S, Mayer J, Trneny M, Zavadil J, Stopka T. MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia. Blood. 2011. Apr 7; 117(14):3816-25. (IF=10.5)


Recent lab research presentations at conferences/symposiums:

  • 2023 XX International Conference on Chronic Lymphocytic Leukemia (iwCLL). Poster: “Coupled effect of a miR-155 deficiency and hypoxia conditions leads to the upregulation of SLC2A1 (GLUT1), SLC2A3 (GLUT3) and EGLN1 genes in the leukemic B-cells".
  • 2021 XIX International Conference on Chronic Lymphocytic Leukemia (iwCLL) - held virtually. Poster: “Effect of miR-155 deficiency in CLL cells on the cell cycle dynamics during normoxia vs hypoxia”.
  • 2021 Virtual EMBO | EMBL Symposium: "The Non-Coding Genome", Heidelberg, Germany. Poster: “Deficiency of miR-155 expression in leukemic B-cells drives changes in cell cycle and cell ploidy”.
  • 2020 Virtual EMBO | EMBL Symposium: "The Complex Life of RNA", Heidelberg, Germany. Poster: “Deletion of miR-155 changes cell ploidy and cell cycle dynamics“.

  • 2019 EMBL/EMBO Symposium: " The non-coding genome", Heidelberg, Germany. Poster: "Study of regulatory miRNA/mRNA network in leukemic B cells using CRISPR/Cas9 technology".
  • 2017 Cell Symposia "CRISPR: From Biology to Technology and Novel Therapeutics", Sitges, Spain. Poster: "Mutagenesis of oncogenic microRNA miR-155 by CRISPR/Cas9 in B-CLL is a tool for deciphering the role of miR-155 targets in CLL".
  • 2017 EMBO/EMBL Symposium "The Non-Coding Genome 2017", Heidelberg, Germany. Abstract book: "Gene editing of oncogenic microRNA miR-155 by CRISPR/Cas9 in CLL: new tool for deciphering of CLL pathogenesis".

Schematical abstracts:


Role of miR-155 in leukemic B-cells (E.Golovina et al, 2024).

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Model of the pathogenic blockade. Indicated by red lines, the B-cell differentiation and CLL pathogenesis involve miR-155/miR-150 network, including its targets MYB and PU.1. Citations are adjacent to the roles of particular molecules. Activation is indicated by arrow, inhibition is indicated by T-shaped arrow (K. Vargova et al. 2017, doi: 10.1038/bcj.2017.63 ).


Alumni:

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MSc. student (2018 - 2022): Bc. Marketa Sypecka ("The molecular basis of B-cell chronic lymphocytic leukemia"). Email: m.sypecka@email.cz


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Guest Ph.D. student, interantional internship (7/2017, 9/2018): MSc. Oxana Yurikova (from Al-Farabi Kazakh National University, Almaty, Kazahstan). Email: oksanayurikova@mail.ru



Guest Ph.D. student, international internship (10/2021): MSc. Monika Cuprych (Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Poland). Email: monika.cuprych@hirszfeld.pl

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Guest Ph.D. student, international internship (Erasmus) (2/2024): MSc. Agata Hahaj-Siembida (University of Life Sciences, Lublin, Poland). Email: agata.hahaj-siembida@up. lublin.pl


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Guest Asst.prof., international internship (Erasmus) (2/2024): Asst.prof. Monika Gregula-Kania, Ph.D. (University of Life Sciences, Lublin, Poland). Email: monika.gregulakania@up.lublin.pl