Laboratory of Genome Integrity

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
BUCHTOVÁ, T., Z. ŠKROTT, K. CHROMÁ, J. ŘEHULKA, P. DŽUBÁK, M. HAJDÚCH, D. LUKÁČ, S. ARAMPATZIS, J. BÁRTEK, M. MISTRÍK
Cannabidiol-induced activation of the metallothionein pathway impedes anticancer effects of disulfiram and its metabolite CuET. Molecular Oncology. 2021, 16(7), 1541-1554, ISSN: 1574-7891, PMID: 34632694,
MISTRÍK, M., Z. ŠKROTT, P. MULLER, A. PANACEK, L. HOCHVALDOVA, K. CHROMÁ, T. BUCHTOVÁ, V. VANDOVA, L. KVÍTEK, J. BÁRTEK
Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response. Nature Communications. 2021, 12(1), 713, ISSN: 2041-1723, PMID: 33514738,
MAYA-MENDOZA, A., P. MOUDRÝ, J. MERCHUT-MAYA, M. LEE, R. STRAUSS, J. BÁRTEK
High speed of fork progression induces DNA replication stress and genomic instability. Nature. 2018, 559(7713), 279-284, ISSN: 0028-0836, PMID: 29950726,
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,
TURI, Z., M. LACEY, M. MISTRÍK, P. MOUDRÝ
Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging. Aging-US. 2019, 11(8), 2512-2540, ISSN: 1945-4589, PMID: 31026227,
MAYA-MENDOZA, A., P. MOUDRÝ, J. MERCHUT-MAYA, M. LEE, R. STRAUSS, J. BÁRTEK
High speed of fork progression induces DNA replication stress and genomic instability. Nature. 2018, 559(7713), 279-284, ISSN: 0028-0836, PMID: 29950726,
BIOAVAILABLE DITHIOCARBAMATE-METAL COMPLEX NANOPARTICLES, METHOD OF PREPARATION AND USE THEREOF "DISULFIRAM I" (Škrott)
  1. Patent: EP 3459526. Granted: 24.2.2021. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  2. Published Application: PCT/EP2018/076098 under WO 2019/063601 (4.4.2019)
  3. Patent: US 11,766,404. Granted: 26.9.2023. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  4. Patent: AU 2018340510. Granted: 5.8.2021. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  5. Published Application: EP 18774051.9 (29.7.2020) - patent pending.
  6. Patent: IL 273652. Granted: 2.1.2024. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  7. Patent: CA 3,076,855. Granted: 26.4.2022. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  8. Patent: KR 10-2456683. Granted: 14.10.2022. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  9. Patent: JP 7149624. Granted: 29.9.2022. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  10. Patent: MX 396,552. Granted: 17.10.2022. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.
  11. Patent:  BR 112020005823-8. Granted: 12.11.2024. Ownership: Palacký University Olomouc. Inventors: Škrott Zdeněk, Mistrík Martin, Hajdúch Marián, Bártek Jiří, Džubák Petr, Zbořil Radek.

Status: Available

METHOD OF OBTAINING FOLLICULAR CELLS AND A DEVICE FOR CARRYING OUT THIS METHOD (Mistrík)
  1. Patent: CZ 304255. Granted: 18.12.2013. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří
  2. Published Application PCT/CZ2013/000152 under WO 2014/086324 (12.6.2014)
  3. Patent: EP 2928382. Granted: 26.12.2018. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří
  4. Patent: US 9,943,331. Granted: 17.4.2018. Ownership: Palacký University Olomouc. Inventors: MISTRÍK Martin, BÁRTEK Jiří
  5. EU Registered Trademark: EUTM 018714735. Registered: 8.11.2022. Ownership: Palacký University Olomouc

Status: Available

Project: Cellular stress in health and disease
Supervisors: Mistrík Martin Ph.D., Moudrý Pavel Ph.D., Škrott Zdeněk Ph.D.
Available: 3
Intended for: Doctoral training

Laboratory head

Research groups

Cellular stress
Senior research group
DNA replication dynamics
Junior research group