RESEARCH INTERESTS

Homeostasis of all multicellular organisms is maintained by an elite set of cells with an unrestrained capacity to differentiate into all cell types – stem cells. Stem cells rely on a rapid rewiring of molecular pathways to maintain tissue integrity and re-populate pools of undifferentiated cells. Loss of these healthy characteristics is a cornerstone of ageing and malignancy.

Orchestrated regulation of post-transcriptional layers of gene expression, in particular mRNA translation and splicing, is an emerging determinant of cell fate choices. How these processes are coordinated to ensure fidelity of stem cell activation and allow for homeostatic balance is largely unknown. Activated stem cells embark on a complex programme that is frequently and notably uncoupled from the transcriptional regulation. How these extra-genomic states are acquired in dynamic stem cell transitions remains a key unanswered question. Similarly, the implications of the ‘non-transcriptional’ regulation of stem cell function were not comprehensively addressed so far. That is a fundamental biological conundrum of how post-transcriptional regulatory networks may be co-opted during the initial stages of stem cells activation. What drives these changes? And for which physiological and pathological processes they are important?

We employ pallet of stem cell systems to study rapid cellular fate switches during development. By a combination of genetic models, genome-wide sequencing approaches and mechanistic and structural technologies, we study function of RNA metabolism during mammalian development. We hope to understand the molecular basis of the post-transcriptional regulation of the stem cell function. With our research, we want to establish molecular underpinnings of pathologies related to stem cell dysfunction, including infertility, congenital diseases, and cancer.

 

MEMBERS OF THE GROUP

Country
Name
Surname
Scientific Degree
Email
Maciej
Cieśla
PhD
m.ciesla@imol.institute
Vladyslava
Liudkovska
PhD
v.liudkovska@imol.institute
Kevork
Wakimian
k.wakimian@imol.institute
 

PUBLICATIONS

2022

  • Pseudouridine-modified tRNA fragments repress aberrant protein synthesis and predict leukemic progression in myelodysplastic syndrome, Guzzi N#, Muthukumar S#, Cieśla M#, Todisco G, Ngoc PCT, Madej M, Munita R, Fazio S, Ekström S, Mortera-Blanco T, Jansson M, Nannya Y, Cazzola M, Ogawa S, Malcovati L, Hellström-Lindberg E, Dimitriou M*, Bellodi C, Nature Cell Biology 2022 in press.

 

2021

  • The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells, Beneventi G, Munita R, Cao Thi Ngoc P, Madej M, Cieśla M, Muthukumar S, Krogh N, Nielsen H, Swaminathan V, Bellodi C, NAR Cancer. 2021 Jul 9;3(3):zcab026. doi: 10.1093/narcan/zcab026. eCollection 2021 Sep.

  • Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer, Cieśla M, Ngoc PCT, Cordero E, Martinez AS, Morsing M, Muthukumar S, Beneventi G, Madej M, Munita R, Jönsson T, Lövgren K, Ebbesson A, Nodin B, Hedenfalk I, Jirström K, Vallon-Christersson J, Honeth G, Staaf J, Incarnato D, Pietras K, Bosch A, Bellodi C., Mol Cell, in press.

 

2020

  • Lack of miR-378 attenuates muscular dystrophy in mdx mice. Podkalicka P, Mucha O, Bronisz-Budzyńska I, Kozakowska M, Pietraszek-Gremplewicz K, Cetnarowska A, Głowniak-Kwitek U, Bukowska-Strakova K, Cieśla M, Kulecka M, Ostrowski J, Mikuła M, Potulska-Chromik A, Kostera-Pruszczyk A, Józkowicz A, Łoboda A, Dulak J. JCI Insight. 2020 Jun 4;5(11):e135576.

  • RNA in Cancer, Ciesla M, Chapter 11 in Rna-Based Regulation in Human Health and Disease (Elsevier), Volume 19 in Translational Epigenetics.

  • Electron paramagnetic resonance spectroscopy reveals alterations in the redox state of endogenous copper and iron complexes in photodynamic stress-induced ischemic mouse liver. Jakubowska MA, Pyka J, Michalczyk-Wetula D, Baczyński K, Cieśla M, Susz A, Ferdek PE, Płonka BK, Fiedor L, Płonka PM. Redox Biol. 2020 Jul;34:101566.

  • Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells. Szade K, Zukowska M, Szade A, Nowak W, Skulimowska I, Ciesla M, Bukowska-Strakova K, Gulati GS, Kachamakova-Trojanowska N, Kusienicka A, Einwallner E, Kijowski J, Czauderna S, Esterbauer H, Benes V, L Weissman I, Dulak J, Jozkowicz A. EMBO Rep. 2020 Feb 5;21(2):e47895.

 

2019

  • Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood. Szade A, Szade K, Nowak WN, Bukowska-Strakova K, Muchova L, Gońka M, Żukowska M, Cieśla M, Kachamakova-Trojanowska N, Rams-Baron M, Ratuszna A, Dulak J, Józkowicz A. EMBO Mol Med. 2019 Dec;11(12):e09571.

  • The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma, Phung B, Cieśla M, Sanna A, Guzzi N, Beneventi G, Ngoc PCT, Lauss M, Cabrita R, Cordero E, Bosch A, Rosengren F, Häkkinen J, Griewank K, Paschen A, Harbst K, Olsson H, Ingvar C, Carneiro A, Tsao H, Schadendorf D, Pietras K, Bellodi C, Jönsson G, Cell Rep;27(12):3573-3586.e7. Joint first authorship.

 

2018

  • Heme Oxygenase-1 Influences Satellite Cells and Progression of Duchenne Muscular Dystrophy in Mice. Pietraszek-Gremplewicz K, Kozakowska M, Bronisz-Budzynska I, Ciesla M, Mucha O, Podkalicka P, Madej M, Glowniak U, Szade K, Stepniewski J, Jez M, Andrysiak K, Bukowska-Strakova K, Kaminska A, Kostera-Pruszczyk A, Jozkowicz A, Loboda A, Dulak J. Antioxid Redox Signal. 2018 Jul 10;29(2):128-148.

  • Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells, Guzzi N, Cieśla M, Ngoc PCT, Lang S, Arora S, Dimitriou M, Pimková K, Sommarin MNE, Munita R, Lubas M, Lim Y, Okuyama K, Soneji S, Karlsson G, Hansson J, Jönsson G, Lund AH, Sigvardsson M, Hellström-Lindberg E, Hsieh AC, Bellodi C. Cell;173(5):1204–1216.

  • Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells, Stepniewski J, Pacholczak T, Skrzypczyk A, Ciesla M, Szade A, Szade K, Bidanel R, Langrzyk A, Grochowski R, Vandermeeren F,  Kachamakova-Trojanowska N,  Jez M, Drabik G,  Nakanishi M,  Jozkowicz A, Dulak J, IUBMB Life. 2018 Jan 9.

 

2017

  • Lack of Heme Oxygenase-1 Induces Inflammatory Reaction and Proliferation of Muscle Satellite Cells after Cardiotoxin-Induced Skeletal Muscle Injury, Kozakowska M, Pietraszek-Gremplewicz K, Ciesla M, Seczynska M, Bronisz-Budzynska I, Podkalicka P, Bukowska-Strakova K, Loboda A, Jozkowicz A, Dulak J, Am J Pathol. 2017 Nov 21. pii: S0002-9440(17)30471-6.

  • Valproic acid downregulates heme oxygenase-1 independently of Nrf2 by increasing ubiquitination and proteasomal degradation, Jez M, Ciesla M, Stepniewski J, Langrzyk A, Muchova L, Vitek L, Jozkowicz A, Dulak J, Biochem Biophys Res Commun, 2017 Mar 25;485(1):160-166.

 

2016

  • Heme oxygenase 1 affects granulopoiesis in mice through control of myelocyte proliferation. Bukowska-Strakova K, Ciesla M, Szade K, Nowak W, Straka R, Szade A, Tyszka-Czochara M, Najder K, Konturek A, Siedlar M, Dulak J, Jozkowicz A. Immunobiology 2016.

  • Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma, Ciesla M, Marona P, Kozakowska M, Jez M, Seczynska M, Loboda A, Bukowska-Strakova K, Szade A, Walawender M, Kusior M, Stepniewski J, Szade K, Krist B, Yagensky O, Urbanik A, Kazanowska B, Dulak J, Jozkowicz A. Cancer Res. 2016 Oct 1;76(19):5707-5718.

 

2015

  • Association of Calcium and Phosphate Balance, Vitamin D, PTH, and Calcitonin in Patients with Adolescent Idiopathic Scoliosis, Goździalska A, Jaśkiewicz J, Knapik-Czajka M, Drąg J, Gawlik M, Cieśla M, Kulis A, Zarzycki D, Lipik E. Spine (Phila Pa 1976). 2016 Apr;41(8):693-7.

  • Myoblast-conditioned media improve regeneration and revascularization of ischemic muscles in diabetic mice. Kozakowska M, Kotlinowski J, Grochot-Przeczek A, Ciesla M, Pilecki B, Derlacz R, Dulak J, Jozkowicz A, Stem Cell Res Ther. 2015 Apr 12; 6:61. 

 

2014

  • MicroRNAs and epigenetic mechanisms of rhabdomyosarcoma development, Cieśla M, Dulak J, Józkowicz A, Int J Biochem Cell Biol. 2014 Aug;53:482-92.

 

2013

  • Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis, Skrzypek K, Tertil M, Golda S, Ciesla M, Weglarczyk K, Collet G, Guichard A, Kozakowska M, Boczkowski J, Was H, Gil T, Kuzdzal J, Muchova L, Vitek L, Loboda A, Jozkowicz A, Kieda C, Dulak J, Antioxid Redox Signal. 2013 Sep 1;19(7):644-60.

  • Development of hyperglycemia and diabetes in captive Polish bank voles, Bartelik A, Ciesla M, Kotlinowski J, Bartelik S, Czaplicki D, Grochot-Przeczek A, Kurowski K, Koteja P, Dulak J, Józkowicz A, Gen Comp Endocrinol. 2013 Mar 1. Joint first authorship.

  • Cross-talk between microRNAs, nuclear factor E2-related factor 2, and heme oxygenase-1 in ochratoxin A-induced toxic effects in renal proximal tubular epithelial cells, Stachurska A, Ciesla M, Kozakowska M, Wolffram S, Boesch-Saadatmandi C, Rimbach G, Jozkowicz A, Dulak J, Loboda A, Mol Nutr Food Res. 2013 Mar.

 

2012

  • Heme oxygenase-1 inhibits myoblast differentiation by targeting myomirs, Kozakowska M, Ciesla M, Stefanska A, Skrzypek K, Was H, Jazwa A, Grochot-Przeczek A, Kotlinowski J, Szymula A, Bartelik A, Mazan M, Yagensky O, Florczyk U, Lemke K, Zebzda A, Dyduch G, Nowak W, Szade K, Stepniewski J, Majka M, Derlacz R, Loboda A, Dulak J, Jozkowicz A, Antioxid Redox Signal. 2012 January 15. Joint first authorship.

 

2011

  • microRNAs as biomarkers of disease onset, Ciesla M, Skrzypek K, Kozakowska M, Łoboda A, Józkowicz A, Dulak J, Anal Bioanal Chem., 2011 May 6.

  • Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington’s disease, Gaughwin PM, Ciesla M, Lahiri N, Tabrizi SJ, Brundin P, Björkqvist M., Hum Mol Genet. 2011 April 1. Joint first authorship.

  • Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134, Gaughwin P, Ciesla M, Yang H, Lim B, Brundin P. Cereb Cortex. 2011 January 12.

 
 

ABOUT GROUP LEADER

SHORT BIO

Dr. Maciej Cieśla has a shared MD and PhD degree from the Jagiellonian University in Poland. For his post-doctoral training with Dr. Cristian Bellodi at Lund Stem Cell Center in Sweden, he studied how splicing factors are controlled at the level of mRNA translation during oncogenic stress. His research focus revolves around understanding of the post-transcriptional gene regulatory networks during cell fate transitions, such as stem cell activation or initial steps of cancerogenesis. In 2021 he joined the ReMedy/IMol PAS to study regulation of splicing in stem cells.

FUNDING

2019

  • postdoctoral research grant from Swedish Cancer Foundation (Cancerfonden).

  • postdoctoral research grant from Swedish Foundation for Medical Research (SSMF). Gratefully declined.

 

2013

  • New model in research on rhabdomyosarcoma development: role of heme oxygenase-1 in rhabdomyosarcoma pathology, Foundation for Polish Science, Ventures program 2013- 11/2.

  • Long-lasting effects of small-molecule inhibitors of heme oxygenase-1 in rhabdomyosarcoma development, grant from the founds of Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University.

  • stipend from Ministry of Higher Education for the best PhD students.

 

2012

  • Influence of small-molecule inhibitors of heme oxygenase-1 on rhabdomyosarcoma development in in vivo animal model, grant from the founds of Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University.

 

2011

  • New strategy for rhabdomyosarcoma treatment: induction of tumor differentiation, Foundation for Polish Science, Ventures program 2011- 7/2.

  • stipends from structural founds of Jagiellonian University, awarded yearly based on the merit.

 

2010

  • Medical Research Council UK Fellowship for Internship at Laboratory of Molecular Biology of Cambridge University.

 

2006

Erasmus-Mundus stipendship