Principal Investigator: RNDr. Karina Savvulidi Vargova, Ph.D.
Email: vargova.mmbd@gmail.com, karin.vargova@lf1.cuni.cz
Lab Members:
Ph.D. student: MSc. Elena Golovina
Topic: 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
Our lab at a glance: Our research activity is focused on the understanding of molecular mechanisms in human B-cell leukemia in relation to miRNA.
Current aim: Elicit how deletion of oncogenic, hypoxiamiR-155 and CDKs in CLL cells affect cell proliferation, cell cycle dynamics under normoxia vs hypoxia conditions. To describe changes in the transcriptome, miRnome and metabolom of miR-155 deficient CLL cells.
Methods: CRISPR/Cas9 technology), Gene Expression Analysis (mRNA, miRNA), Sequencing Proteomics, Coy hypoxic glove box and other advanced techniques (cell sorting by FACS, Image cytometry, Fluorescence microscopy).
Funding: PRIMUS/17/MED/16 (2018-2021)
Main collaboration (knowledge sharing):
- Biocev, Laboratory of Prof. Tomas Stopka, MD, PhD (http://stopka-lab.lf1.cuni.cz/en/about-our-lab)
Other collaborations:
- Institute of Pathological Physiology, Lymphoma Lab (Pavel Klener, MD, PhD, associated prof.)
- Center for Advanced Preclinical Imaging, Prague, Czech Republic (RNDr. Ludek Sefc, CSc.)
- Biocev, Phenogenomics, Vestec, Czech Republic (Prof. Radek Sedlacek, PhD, MVDr. Jan Kucera)
- Center of the Region Hana for Biotechnological and Agricultural research, Faculty of Science, Palacky University, Olomouc (Prof. Marek Sebela, PhD)
- Institute de Genomique, Centre National de Genotypage (CNG), Paris, France (Jorg Tost, PhD)
- Al-Farabi Kazakh National University, Faculty of Biology and Biotechnology. Almaty, Kazakhstan (MSc. Oxana Yurikova)
Key related publications:
· 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
· 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
· 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/symposium:
- 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".
- 2019 Cell Symposia "Regulatory RNA", Berlin, Germany. Poster: "Deciphering the role of miR-155 targets in chronic lymphocytic leukemia by direct editing of miR-155 in the leukemic B-cells using CRISPR/Cas9"(file:///C:/Users/Karin/
Desktop/2019_poster_Cell_ Symposium_Berlin/190509_ poster_Berlin_final02/index. html )
- 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".
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 (Vargova et al. 2017, doi: 10.1038/bcj.2017.63 ).
Alumni:
MSc. student (2018 - 2021): Bc. Marketa Sypecka ("The molecular basis of B-cell chronic lymphocytic leukemia"). Email: m.sypecka@email.cz
Guest Ph.D. student, internship (7/2017, 9/2018): MSc. Oxana Yurikova (from Al-Farabi Kazakh National University). Email: oksanayurikova@mail.ru
Guest Ph.D. student, internship (10/2021): MSc. Monika Cuprych (Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences). Email: monika.cuprych@hirszfeld.pl
