Laboratory of Genome Integrity
Head: Martin Mistrík
Olomouc node
HOME INSTITUTION
Faculty of Medicine PU in Olomouc
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
Cancer hides, grows, and decays from within, one must be cunning!
- Mission: Transforming cancer research and treatment using insights into how cells handle different forms of stress.
- Vision: We will bring new treatments that target specific weaknesses of tumor cells.
LIG’s research focuses on understanding the molecular differences between cancer and healthy body cells. We employ a comprehensive array of methodologies to elucidate these distinctions. Our experimental approaches include exposing tumor cells to gamma radiation, UV light, elevated temperatures, mechanical stress, and various chemicals—effectively creating a constellation of stress factors. By monitoring the biological responses at the molecular level, particularly the activation of specific stress pathways, we aim to uncover the fundamental vulnerabilities of tumor cells.
SELECTED PUBLICATIONS
- Mistrik M, Skrott Z, Muller P, Panacek A, Hochvaldova L, Chroma K, Buchtova T, Vandova V, Kvitek L, Bartek J. Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response. Nat Commun. 2021 Jan 29;12(1):713. DOI: 10.1038/s41467-021-20989-9
- Chroma K, Skrott Z, Gursky J, Bacovsky J, Moudry P, Buchtova T, Mistrik M, Bartek J. A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment. Cell Death Dis. 2022 Mar 4;13(3):203. DOI: 10.1038/s41419-022-04651-w
- Skrott Z, Majera D, Gursky J, Buchtova T, Hajduch M, Mistrik M, Bartek J. Disulfiram’s anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase. Oncogene. 2019 Oct;38(40):6711-6722. DOI: 10.1038/s41388-019-0915-2
- Skrott Z, Mistrik M, Andersen KK, Friis S, Majera D, Gursky J, Ozdian T, Bartkova J, Turi Z, Moudry P, Kraus M, Michalova M, Vaclavkova J, Dzubak P, Vrobel I, Pouckova P, Sedlacek J, Miklovicova A, Kutt A, Li J, Mattova J, Driessen C, Dou QP, Olsen J, Hajduch M, Cvek B, Deshaies RJ, Bartek J. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature. 2017 Dec 14;552(7684):194-199. DOI: 10.1038/nature25016
- Chroma K, Mistrik M, Moudry P, Gursky J, Liptay M, Strauss R, Skrott Z, Vrtel R, Bartkova J, Kramara J, Bartek J. Tumors overexpressing RNF168 show altered DNA repair and responses to genotoxic treatments, genomic instability and resistance to proteotoxic stress. Oncogene. 2017 Apr 27;36(17):2405-2422. DOI: 10.1038/onc.2016.392
COLLABORATION WITHIN THE NICR
Jan Bouchal
(Olomouc node, Faculty of Medicine PU in Olomouc)
Libor Macůrek
(Prague node, Institute of Molecular Genetics of the Czech Academy of Sciences)
Marián Hajdúch
(Olomouc node, Faculty of Medicine PU in Olomouc)
Miloš Petřík
(Olomouc node, Faculty of Medicine PU in Olomouc)
Ondřej Slabý
(Brno node, Faculty of Medicine MU/CEITEC MU)
Petr Džubák
(Olomouc node, Faculty of Medicine PU in Olomouc)
Petr Müller
(Brno node, Masaryk Memorial Cancer Institute)
Vladimír Divoký
(Olomouc node, Faculty of Medicine PU in Olomouc)
Vladimír Kryštof
(Olomouc node, Faculty of Medicine PU in Olomouc)
Zdeněk Hodný
(Prague node, Institute of Molecular Genetics of the Czech Academy of Sciences)
SPECIALIZED EXPERTISE AND TECHNOLOGY
Advanced microscopy techniques, photo manipulation, super-resolution, live-cell imaging
Extensive collection of reporter cell models for real-time analysis of cellular stress pathways
Technology for the induction and monitoring of various cellular stresses – genotoxic stress, thermal stress, radical stress, replication stress, modulation of cellular metabolism
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
National infrastructure for biological and biomedical imaging Czech-Bioimaging
National infrastructure for translational medicine EATRIS-CZ