Laboratory of Genome Integrity
Head: Zdeněk Hodný
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 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
Things are not always as they seem.
- Mission: To elucidate the promalignant effects of therapy-induced cellular senescence in glioblastoma.
- Vision: To identify the molecular mechanisms of invasive glioblastoma growth and the role of cellular senescence.
Glioblastoma (grade IV astrocytoma) is a brain tumor with a poor prognosis, even with the most advanced treatments available. The current genotoxic treatments of malignant tumors, which include radiotherapy and chemotherapy, often lead to the development of cellular senescence within the tumor tissues. Senescent cells secrete several bioactive factors such as proinflammatory cytokines and TGFbeta family morphogens, which can enhance the malignant properties of tumor cells, including their proliferation, migration and invasiveness, stemness, and resistance to therapy. The composition of the secretome of senescent cells can vary depending on the type of tissue, the inducer of senescence, and the interactions between cells. However, the senescent secretome of brain tumor tissue before and after genotoxic therapy is unknown.
SELECTED PUBLICATIONS
- Novakova Z, Hubackova S, Kosar M, Janderova-Rossmeislova L, Dobrovolna J, Vasicova P, Vancurova M, Horejsi Z, Hozak P, Bartek J, Hodny Z. Cytokine expression and signaling in drug-induced cellular senescence. Oncogene. 2010 29:273-284. DOI: 10.1038/onc.2009.318
- Hubackova S, Kucerova A, Michlits G, Kyjacova L, Reinis M, Korolov O, Bartek J, Hodny Z. IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2. Oncogene. 2016 Mar 10;35(10):1236-49. DOI: 10.1038/onc.2015.162
- Hubackova S, Pribyl M, Kyjacova L, Moudra A, Dzijak R, Salovska B, Strnad H, Tambor V, Imrichova T, Svec J, Vodicka P, Vaclavikova R, Rob L, Bartek J, Hodny Z. Interferon-regulated suprabasin is essential for stress-induced stem-like cell conversion and therapy resistance of human malignancies. Mol Oncol. 2019 Jul;13(7):1467-1489. DOI: 10.1002/1878-0261.12480
- Kyjacova L, Hubackova S, Krejcikova K, Strauss R, Hanzlikova H, Dzijak R, Imrichova T, Simova J, Reinis M, Bartek J, Hodny Z. Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells. Cell Death Differ. 2015 Jun;22(6):898-911. DOI: 10.1038/cdd.2014.97
- Salovska B, Kondelova A, Pimkova K, Liblova Z, Pribyl M, Fabrik I, Bartek J, Vajrychova M, Hodny Z. Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape. Redox Biol. 2022 Feb;49:102212. DOI: 10.1016/j.redox.2021.102212
COLLABORATION WITHIN THE NICR
Martin Sztacho
(Prague node, First Faculty of Medicine CU)
Pavel Dráber
(Prague node, Institute of Molecular Genetics of the Czech Academy of Sciences)
SPECIALIZED EXPERTISE AND TECHNOLOGY
2D and 3D models ant methods for testing new potential drugs
Advanced microscopic techniques, including higthroughput time-lapse microscopy
Proteomics and bioinformatics
Advanced methods of molecular and cell biology
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
National infrastructure for biological and biomedical imaging Czech-Bioimaging
National Infrastructure for Chemical Biology CZ-OPENSCREEN