Laboratory of Cancer Cell Biology
Head: Libor Macůrek
Prague node
HOME INSTITUTION
Institute of Molecular Genetics of the Czech Academy of Sciences
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 3 - Biomarkers of cancers and cancer diagnostics
Genome instability as cause and Achilles heel of cancer.
- Mission: We wish to uncover how genetic instability promotes cancer and if it could be targeted in cancer therapy.
- Vision: By identifying the genetically defined risk factors we will prevent cancer development.
Genome instability is one of the hallmarks of cancer. Hereditary as well as sporadic tumors commonly carry inactivating mutations in genes involved in DNA repair and cell cycle checkpoints. Mutations in these genes promote genome instability, activation of oncogenes, inactivation of tumor suppressors and cell transformation. Laboratory of cancer cell biology investigates molecular mechanisms of DNA repair and cell cycle control. By combining proteomic approaches, superresolution microscopy and biochemical assays, we investigate the role of protein phosphorylation in organization of the chromatin complexes, mitotic spindle and tumor metabolism. Subsequently, we validate the oncogenic potential of identified defects in these pathways using transgenic mouse models. Defects in DNA repair not only promote cell transformation but can also influence the tumor sensitivity to treatment. Understanding of defects in DNA repair in individual tumors can therefore contribute to rational use of chemotherapeutics and to personalized treatment.
SELECTED PUBLICATIONS
- Burocziova M, Danek P, Oravetzova A, Chalupova Z, Alberich-Jorda M, Macurek L. Ppm1d truncating mutations promote the development of genotoxic stress-induced AML. Leukemia. 2023; 37:2209-2220. DOI: 10.1038/s41375-023-02030-8
- Storchova R, Palek M, Palkova N, Veverka P, Brom T, Hofr C, Macurek L. Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres. Nucleic Acids Research. 2023; 51:1154-1172. DOI: 10.1093/nar/gkac1269
- Aquino Perez C, Burocziova M, Jenikova G, Macurek L. CK1-mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment. EMBO Reports. 2021; 22:e51847. DOI: 10.15252/embr.202051847
- Burocziova M, Burdova K, Martinikova AS, Kasparek P, Kleiblova P, Danielsen SA, Borecka M, Jenikova G, Kleibl Z, Lothe RA, Korinek V, Macurek L. Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon. Cell Death & Disease. 2019; 10:818. DOI: 10.1038/s41419-019-2057-4
- Stolarova L, Kleiblova P, Zemankova P, Stastna B, Janatova M, Soukupova J, Achatz MI, Ambrosone C, Apostolou P, Arun BK, Auer P, Barnard M, Bertelsen B; Biobank Japan; Blok MJ, Boddicker N, Brunet J, Burnside ES, Calvello M, Campbell I, Chan SH, Chen F, Chiang JB, Coppa A, Cortesi L, Crujeiras-González A; Consortium CZECANCA; De Leeneer K, De Putter R, DePersia A, Devereux L, Domchek S, Efremidis A, Engel C, Ernst C, Evans DGR, Feliubadaló L, Fostira F, Fuentes-Ríos O, Gómez-García EB, González S, Haiman C, Hansen TVO, Hauke J, Hodge J, Hu C, Huang H, Ishak NDB, Iwasaki Y, Konstantopoulou I, Kraft P, Lacey J, Lázaro C, Li N, Lim WK, Lindstrom S, Lori A, Martinez E, Martins A, Matsuda K, Matullo G, McInerny S, Michailidou K, Montagna M, Monteiro ANA, Mori L, Nathanson K, Neuhausen SL, Nevanlinna H, Olson JE, Palmer J, Pasini B, Patel A, Piane M, Poppe B, Radice P, Renieri A, Resta N, Richardson ME, Rosseel T, Ruddy KJ, Santamariña M, Dos Santos ES, Teras L, Toland AE, Trentham-Dietz A, Vachon CM, Volk AE, Weber-Lassalle N, Weitzel JN, Wiesmuller L, Winham S, Yadav S, Yannoukakos D, Yao S, Zampiga V, Zethoven M, Zhang ZW, Zima T, Spurdle AB, Vega A, Rossing M, Del Valle J, De Nicolo A, Hahnen E, Claes KBM, Ngeow J, Momozawa Y, James PA, Couch FJ, Macurek L, Kleibl Z. ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk. Clin Cancer Res. 2023; 29:3037-3050. DOI: 10.1158/1078-0432.CCR-23-0212
- Jaiswal H, Benada J, Müllers E, Akopyan K, Burdova K, Kolmeister T, Heleday T, Medema R, Macurek L, Lindqvist A. ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration. EMBO Journal. 2017; 36:2161-2176. DOI: 10.15252/embj.201696082
COLLABORATION WITHIN THE NICR
SPECIALIZED EXPERTISE AND TECHNOLOGY
Cell cycle control and genome integrity
Tumor supressor p53
High-content microscopy Olympus ScanR station
Genome editing by CRISPR/Cas9
Cell/molecular biology techniques
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
National infrastructure for biological and biomedical imaging Czech-Bioimaging
Czech Centre for Phenogenomics CCP
Biotechnology and Biomedicine Centre of the Czech Academy of Sciences and the Charles University BIOCEV