Mechanisms involved in remodeling of chromatin structure during cell fate decisions

Mechanisms involved in remodeling of chromatin structure during cell fate decisions

Prof. MUDr. Tomáš Stopka, Ph.D.

Prof. MUDr. Tomáš Stopka, Ph.D. — Project head

About us

Project focuses on studying the function of chromatin remodeling ISWI ATPase Smarca5 (Snf2h, MommeD4, Iswi) in the development of haematopoiesis from stem and progenitor cells and to understand their involvement in leukaemogenesis. Chromatin, a nucleoprotein complex engaged in the transfer of biological information, is made accessible (or inaccessible) upon activities of enzymes that belong to SWI/SNF2 family.

SWI/SNF2 proteins, namely Smarca5, can regulate the interaction between DNA and histones and allow or block cell decisions imposed by recruitments of these factors. Importantly, Smarca5 interacts with several hematopoietic transcription factors, whose role is also a focus in our plans, as well as to understand target genetic programs of Smarca5-complexes.

 

We aim:

  • To understand mechanisms that during development are involved in regulating cell fate decisions at the level of chromatin and Smarca5.
  • To elucidate role of Smarca5 in lineage-specific processes involving differentiation and lineage commitment using proposed set of transgenic animals that enable tissue specific knockout and overexpression.
  • To understand how disruption of mechanisms involving Smarca5 and their partners may lead to haematologic malignancies.

 

Further information can be found at www.phenogenomics.cz or at group link: http://stopka-lab.lf1.cuni.cz/

News

Events

Publications

2019

Zikmund T, Kokavec J, Turkova T, Savvulidi F, Paszekova H, Vodenkova S,
Sedlacek R, Skoultchi AI, Stopka T. ISWI ATPase Smarca5 Regulates Differentiation
of Thymocytes Undergoing β-Selection. J Immunol. 2019 Jun 15;202(12):3434-3446.
doi: 10.4049/jimmunol.1801684.

Skalicka P, Dudakova L, Palos M, Huna LJ, Evans CJ, Mahelkova G, Meliska M, Stopka T, Tuft S, Liskova P. Paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance (MGUS): clinical findings in twelve patients including recurrence after keratoplasty. Acta Ophthalmol. 2019 May 2. doi: 10.1111/aos.14123. (IF 3.032)

Minarik L, Zemanova Z, Kulvait V, Dluhosova M, Jonasova A and Stopka T. Azacitidine Switch to Lenalidomide Eradicated the TP53/ CDKN2A Co-Mutated Clone and Induced Long-Term Erythroid Response in Del(5q) MDS. Ann Hematol Oncol. 2019; 6(1): 0000. (IF 2.219)

2018

Srutova K, Curik N, Burda P, Savvulidi F, Silvestri G, Trotta R, Klamova H, Pecherkova P, Sovova Z, Koblihova J, Stopka T, Perrotti D, Polakova KM. BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia. Haematologica. 2018 Dec;103(12):2016-2025. doi: 10.3324/haematol.2018.193086. (IF 9.09)

Jonasova A, Neuwirtova R, Polackova H, Siskova M, Stopka T, Cmunt E, Belickova M, Moudra A, Minarik L, Fuchs O, Michalova K, Zemanova Z. Lenalidomide treatment in lower risk myelodysplastic syndromes-The experience of a Czech hematology center. (Positive effect of erythropoietin ± prednisone addition to lenalidomide in refractory or relapsed patients). Leuk Res. 2018 Jun;69:12-17. doi:10.1016/j.leukres.2018.03.015. (IF 2.319)

2017

Kokavec J, Zikmund T, Savvulidi F, Kulvait V, Edelmann W, Skoultchi AI, Stopka T. The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells. Stem Cells. 2017 Jun;35(6):1614-1623. doi: 10.1002/stem.2604. (IF: 5.599)

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 Jul 10. doi: 10.1038/onc.2017.215. (IF: 7.519)

Vargova K, Pesta M, Obrtlíkova P, Dusilkova N, Minarik L, Vargova J, Berkova A, Zemanova Z, Michalova K, Spacek M, Trneny M and 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: 6.126)

Polgarova K, Vargova K, Kulvait V, Dusilkova N, Minarik L, Zemanova Z, Pesta M, Jonasova A, Stopka T. Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selection in patients-responders. Oncotarget. 2017 Dec 6;8(67):111966-111978. doi: 10.18632/oncotarget.22957. (IF 5.168)

Dusílková N, Bašová P, Polívka J, Kodet O, Kulvait V, Pešta M, Trněný M, Stopka T. Plasma miR-155, miR-203, and miR-205 are Biomarkers for Monitoring of Primary Cutaneous T-Cell Lymphomas. Int J Mol Sci. 2017 Oct 15;18(10). pii:E2136. doi: 10.3390/ijms18102136. (IF 3.226)

Bašová P, Pešta M, Sochor M, Stopka T. Prediction Potential of Serum miR-155 and miR-24 for Relapsing Early Breast Cancer. Int J Mol Sci. 2017 Oct 10;18(10). pii: E2116. doi: 10.3390/ijms18102116. (IF 3.226)

2016

He S, Limi S, McGreal RS, Xie Q, Brennan LA, Kantorow WL, Kokavec J, Majumdar R, Hou H Jr, Edelmann W, Liu W, Ashery-Padan R, Zavadil J, Kantorow M, Skoultchi AI, Stopka T, Cvekl A. Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation. Development. 2016 Jun 1;143(11):1937-47. doi: 10.1242/dev.135285..

DN Papageorgiou, E Karkoulia, A Amaral-Psarris, P Burda, K Kolodziej, JA Demmers, J Bungert, T Stopka, J Strouboulis. Distinct and overlapping DNMT1 interactions with multiple transcription factors in erythroid cells: evidence for co-repressor functions. Biochim Biophys Acta. 2016 Dec;1859(12):1515-1526. doi: 10.1016/j.bbagrm.2016.09.007.

P Burda, J. Vargova, N Curik, C Salek, G Papadopoulos, J Strouboulis and T. Stopka. GATA-1 inhibits PU.1 gene via DNA and histone H3K9 Methylation of its Distal Enhancer in Erythroleukemia. PLoS One, 2016 Mar 24;11(3):e0152234

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. (IF: 6.126)

2014

Dluhosova M, Curik N, Vargova J, Jonasova A, Zikmund T, Stopka T. Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5. PLoS One. 2014 Feb 3;9(2):e87448. doi: 10.1371/journal.pone.0087448. eCollection 2014

Dluhosova M, Curik N, Vargova J, Jonasova A, Zikmund T,Stopka T. Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5. PLoS One. 2014 Feb 3;9(2):e87448.

Alvarez-Saavedra M, De Repentigny Y, Lagali PS, Raghu Ram EV, Yan K, Hashem E, Ivanochko D, Huh MS, Yang D, Mears AJ, Todd MA, Corcoran CP, Bassett EA, Tokarew NJ, Kokavec J, Majumder R, Ioshikhes I, Wallace VA, Kothary R, Meshorer E, Stopka T, Skoultchi AI, Picketts DJ. Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation. Nat Commun. 2014 Jun 20;5:4181 (IF:11.470)

2013

Basova P, Pospisil V, Savvulidi F, Burda P, Vargova K, Stanek L, Dluhosova M, Kuzmova E, Jonasova A, Steidl U, Laslo P, Stopka T.: Aggressive acute myeloid leukemia in PU.1/p53 double-mutant mice. Oncogene. 2013 Oct 14.
doi: 10.1038/onc.2013.414

Machova Polakova K, Koblihova J, Stopka T.: Role of epigenetics in chronic myeloid leukemia. Curr Hematol Malig Rep. 2013 Mar;8(1):28-36.

doi: 10.1007/s11899-012-0152-z

Machova Polakova K, Koblihova J, Stopka T. Role of epigenetics in chronic myeloid leukemia. Curr Hematol Malig Rep. 2013 Mar;8(1):28-36. doi: 10.1007/s11899-012-0152-z. (IF: 2.3)

Team

Prof. MUDr. Tomáš Stopka, Ph.D.

Prof. MUDr.
Tomáš Stopka, Ph.D.

Head of Group Mechanisms involved in remodeling of chromatin structure during cell fate decisions

tomas.stopka@lf1.cuni.cz
+420325873001
Mgr. Petra Bašová, Ph.D.

Mgr.
Petra Bašová, Ph.D.

Junior researcher

petra.basova@lf1.cuni.cz
+420325873003
Mgr. Juraj Kokavec, Ph.D.

Mgr.
Juraj Kokavec, Ph.D.

Junior researcher

juraj.kokavec@lf1.cuni.cz
+420325873002
Mgr. Vojtěch Kulvait, Ph.D.

Mgr.
Vojtěch Kulvait, Ph.D.

vojtech.kulvait@lf1.cuni.cz
+420325873002
Mgr. Tomáš Zikmund

Mgr.
Tomáš Zikmund

PhD student

tomas.zikmund@lf1.cuni.cz
+420325873002
Mgr. Tereza Turková

Mgr.
Tereza Turková

PhD student

tereza.turkova@lf1.cuni.cz
+420325873002
MUDr. Ľubomír Minařík

MUDr.
Ľubomír Minařík

Junior researcher

lubomir.minarik@lf1.cuni.cz
+420325873026
MUDr. Adéla Schaffartzik

MUDr.
Adéla Schaffartzik

PhD student

adela.schaffartzik@lf1.cuni.cz
+420325873026
MUDr. Nina Dusílková

MUDr.
Nina Dusílková

PhD student

nina.dusilkova@lf1.cuni.cz
+420325873026
RNDr. Pavel Čabart, CSc.

RNDr.
Pavel Čabart, CSc.

Senior researcher

pavel.cabart@lf1.cuni.cz
+420325873013