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Research at the Laboratory of Integrative Genomics (LIG) centers on elucidating the molecular mechanisms governing DNA damage response and cellular stress pathways. These pathways are activated by a myriad of factors including, but not limited to, erroneous DNA replication, proteotoxicity, mechanical strain, and oxidative damage. Such pathways are pivotal for the sustenance of cancer cells and play a crucial role in conferring therapeutic resistance.

Our investigatory focus encompasses a wide range of cancer-specific hallmarks, such as heightened levels of DNA damage concomitant with mutational burden, challenges in DNA replication fidelity, accumulation of misfolded or dysfunctional proteins, free radical generation, nutrient scarcity, and hypoxic conditions. Through our specialized methods and domain expertise, we aim to directly interrogate and target these stress pathways within the cancer cellular milieu.

The implications of our research are manifold. They extend from the discovery of novel predictive markers to the optimization of existing anticancer regimens and the identification of innovative therapeutic targets. To achieve these aims, the laboratory is segmented into two primary research arms:

The "Cellular Stress" group, headed by Dr. Martin Mistrik, focuses on deciphering the complexities of cellular stress responses and their roles in cancer pathology.

The "DNA Replication Dynamics" group, under the direction of Dr. Pavel Moudry, specializes in exploring the intricacies of DNA replication processes, specifically in the context of malignancies.

  • DNA damage and repair and genomic instability
  • Proteotoxic stress and proteostasis
  • Mechanical stress
  • Oncogenic and free radicals stress
  • DNA replication and replication stress
  • PARP enzyme and its targeting
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments. Life Science Alliance. 2022, 5(12), e202201560, ISSN: 2575-1077, PMID: 36260751,
CHROMÁ, K., Z. ŠKROTT, J. GURSKÝ, J. BACOVSKY, P. MOUDRÝ, T. BUCHTOVÁ, M. MISTRÍK, J. BÁRTEK
A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment. Cell Death & Disease. 2022, 13(3), 203, ISSN: 2041-4889, PMID: 35246527,
MOUDRÝ, P., K. CHROMÁ, S. BURSAC, S. VOLAREVIC, J. BÁRTEK
RNA-interference screen for p53 regulators unveils a role of WDR75 in ribosome biogenesis. Cell Death and Differentiation. 2022, 29(3), 687-696, ISSN: 1350-9047, PMID: 34611297,
DNA polymerase α-primase facilitates PARP inhibitor-induced fork acceleration and protects BRCA1-deficient cells against ssDNA gaps. Nature Communications. 2024, 15(1), 7375, ISSN: 2041-1723, PMID: 39191785,  PDF.
BUCHTOVÁ, T., D. LUKÁČ, Z. ŠKROTT, K. CHROMÁ, J. BÁRTEK, M. MISTRÍK
Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics. International Journal of Molecular Sciences. 2023, 24(3), 2885, ISSN: 1422-0067, PMID: 36769206,  PDF.
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments. Life Science Alliance. 2022, 5(12), e202201560, ISSN: 2575-1077, PMID: 36260751,
LIQUID CHROMATOGRAPHY COLUMN (Mistrík)

Utility Model: CZ 35118. Granted: 1.6.2021. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, ŠKROTT Zdeněk, OŽDIAN Tomáš.

Status: Available

REMOVABLE CULTURE KIT FOR CELL CULTURES GROWN ON CULTURE DISHES (Mistrík)

Utility Model: CZ 34546. Granted: 16.11.2020. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří

Status: Available

MOLECULAR COMPLEX ASSEMBLY PARTICLES COMRISING BIS-R1, R2-DITHIOCARBAMATE-METAL COMPLEX AND A LIGAND, METHOD OF PREPARATION AND USE THEREOF "DISULFIRAM II" (Mistrík)
  1. Published Application EP 18199181.1 under EP 3636285 (15.4.2020)
  2. Published Application PCT/EP2019/077222 under WO 2020/074514 (16.4.2020)
  3. Patent: AU 2019358428. Granted: 17.11.2022. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří, ŠKROTT Zdeněk, DŽUBÁK PetrHAJDÚCH Marián
  4. Patent: CA 3,114,031. Granted: 12.3.2024. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří, ŠKROTT Zdeněk, DŽUBÁK PetrHAJDÚCH Marián
  5. Patent: IL 281616. Granted: 2.4.2024. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří, ŠKROTT Zdeněk, DŽUBÁK PetrHAJDÚCH Marián
  6. Patent: JP 7220932. Granted: 3.2.2023. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří, ŠKROTT Zdeněk, DŽUBÁK PetrHAJDÚCH Marián
  7. Patent: KR 10-2626651. Granted: 17.1.2024. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří, ŠKROTT Zdeněk, DŽUBÁK PetrHAJDÚCH Marián

Status: Patents pending, Available

Projekt: Cellular stress in health and disease
Vedoucí: Mistrík Martin Ph.D., Moudrý Pavel Ph.D., Škrott Zdeněk Ph.D.
K dispozici: 3
Určeno pro: Doktorské studium
Senior research group
Junior research group