DNA in our cells is constantly damaged by various internal and external factors. To maintain genomic stability, the cells develop multiple DNA repair pathways. Mutations in DNA repair genes lead to disorders in humans. Non-Homologous End-Joining (NHEJ) fixes the DNA double-strand breaks (DSB) throughout the cell cycle. NHEJ is required for the development of immune and nervous systems and to suppress medulloblastoma.
NHEJ consists of Ku70, Ku80, XLF, XRCC4, DNA Ligase 4, DNA-PKcs, Artemis, XLS/PAXX, APLF, Mri/Cyren. There is a complex genetic interaction between the NHEJ factors (eg, Oksenych et al., PNAS, 2013; Xing et al., DNA repair, 2017; Castaneda-Zegarra et al., DNA repair, 2019; Xing and Oksenych, FEBS open bio, 2019; Castaneda-Zegarra et al., Aging, 2020; Castaneda-Zegarra et al., Scandinavian Journal of Immunology, 2020).
In response to DNA damage, there is a complex process that includes the activation of multiple enzymes and modifications of proteins, such as histones surrounding the DSBs. This process is called the DNA damage response (DDR) pathway. It is facilitated by protein kinases ATM and DNA-PKcs, scaffold proteins MDC1 and 53BP1, ubiquitin-ligases RNF8 and RNF168, and many other proteins. During the DDR, histones are phosphorylated, ubiquitylated, methylated, acetylated, SUMOylated, NEDDylated, etc (Zha et al., Nature, 2011; Oksencyh et al., PNAS, 2012; Kumar et al., DNA repair, 2014; Beck et al. al., Biomolecules, 2020). I am attempting to understand the complexity of DDR, as well as its role in the development of the immune system and in cancer suppression.
Both NHEJ and DDR pathways are involved in immune system development, including the V(D)J recombination in developing B and T lymphocytes, and the Class Switch Recombination (CSR) in mature B cells.
Translocations associated with V(D)J recombination and class switch recombination (CSR) can be detected using High Throughput Genome-Wide Translocation sequencing (HTGTS). I collaborate with researchers at Karolinska Institutet and Harvard Medical School to develop HTGTS-based assays using primary human B cells.
Several drug candidates were identified to be used in cancer and immune disease treatments. I collaborate with researchers at UiO and local hospitals to validate and select the best options for further translation to the clinic.
2015-2022. Researcher, principal investigator. NTNU – Trondheim, Norway
2021-2022. Lecturer. University of Stavanger, Stavanger, Norway
2020-2022.Researcher. University of Oslo, Oslo, Norway
2020-2020. Researcher. The Arctic University of Norway – Tromsø (UiT)
2018-2020. Visiting Researcher. Karolinska Institutet, Sweden
2014-2015. Postdoc. University of Copenhagen, Denmark
2010-2014. Postdoc. Harvard Medical School, USA
2005-2009. PhD candidate. IGBMC, University of Strasbourg, France
Past projects and awards
2020-2021. Karolinska Institutet (KI Foundations and Funds). #2020-02155
2020-2021. Health Authority of Central Norway. #38811
2019-2022. Award in innovation, enabling technologies, NTNU, Norway
2018-2019. NTNU PES and POS grants, Norway
2018-2019. Research Council of Norway, FRIPRO. #291217
2017-2021. Outstanding Academic Fellow Award, NTNU, Norway
2017-2020. Norwegian Cancer Society, Open call. #182355
2016-2019. Research Council of Norway, FRIMEDBIO. #249774
2016-2018. Research Council of Norway, FRIPRO. #270491
2016-2018. Health Authority of Central Norway. #13477
2015-2017. Lundbeck Fellowship, University of Copenhagen, Denmark
2008-2009. Anti-Cancer Research Association (ARC), France
2007-2008. Anti-Cancer Research Association (ARC), France
2005 Mobility grant, IBB – Academy of Science, Warsaw, Poland
- (2023). Tyrosine Kinase Inhibitors Target B Lymphocytes. Biomolecules.
- (2023). Therapeutic Effectiveness of Interferon-α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience. International Journal of Molecular Sciences.
- (2023). The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin. Biomedicine & Pharmacotherapy.
- (2023). Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment. Pharmaceuticals. 14 sider.
- (2023). Cardioprotective Activity of Pharmacological Agents Affecting NO Production and Bioavailability in the Early Postnatal Period after Intrauterine Hypoxia in Rats. Biomedicines.
- (2023). Association of Myocardial Changes and Gene Expression of the NFATC1 and NFATC4—Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve. Children.
- (2022). Seven classes of antiviral agents. Cellular and Molecular Life Sciences (CMLS).
- (2022). Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses. Current Issues in Molecular Biology. 5728-5740.
- (2022). Novel Synergistic Anti-Enteroviral Drug Combinations. Viruses. 7 sider.
- (2022). DrugVirus.info 2.0: an integrative data portal for broad-spectrum antivirals (BSA) and BSA-containing drug combinations (BCCs). Nucleic Acids Research (NAR). W272-W275.
- (2021). Synergistic interferon-alpha-based combinations for treatment of sars-cov-2 and other viral infections. Viruses. 1-18.
- (2021). Nafamostat–interferon-α combination suppresses sars-cov-2 infection in vitro and in vivo by cooperatively targeting host tmprss2. Viruses. 1-8.
- (2021). Active components of commonly prescribed medicines affect influenza a virus–host cell interaction: A pilot study. Viruses. 1-14.
- (2021). Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice. Biomolecules. 1-10.
- (2020). Potential Antiviral Options against SARS-CoV-2 Infection. Viruses. Viruses. E642.
- (2020). Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population. Biomolecules. 1-13.
- (2020). Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF. Biomolecules.
- (2020). Leaky severe combined immunodeficiency in mice lacking non-homologous end joining factors XLF and MRI. Aging. 23578-23597.
- (2020). Identification and Tracking of Antiviral Drug Combinations. Viruses.
- (2020). Chemical, Physical and Biological Triggers of Evolutionary Sonserved Bcl-xL-Mediated Apoptosis. Cancers. 1-19.
- (2019). Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53. DNA Repair. 164-169.
- (2019). Low temperature and low UV indexes correlated with peaks of influenza virus activity in Northern Europe during 2010-2018. Viruses. 1-10.
- (2019). Genetic interaction between DNA repair factors PAXX, XLF, XRCC4 and DNA-PKcs in human cells. FEBS Open Bio. 1315-1326.
- (2019). Generation of a mouse model lacking the non-homologous end-joining factor Mri/Cyren. Biomolecules. 1-13.
- (2019). Common nodes of virus-host interaction revealed through an integrated network analysis. Frontiers in Immunology. 12 sider.
- (2018). Robust DNA repair in PAXX-deficient mammalian cells. FEBS Open Bio. 442-448.
- (2018). Novel activities of safe-in-human broad-spectrum antiviral agents. Antiviral Research. 174-182.
- (2018). Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF. FEBS Open Bio. 426-434.
- (2017). Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70. DNA Repair. 133-138.
- (2017). Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. Viruses.
- (2019). Critical Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis.
- (2019). Critical Nodes of Viral Modulation Revealed Through an Integrated Network Analysis of Host-Virus Interaction Landscape.
- (2023). Editorial: Plasticity of immune cells in tumor microenvironment. Frontiers in Oncology.
- (2023). DNA Repair and Immune Response: Editorial. Biomolecules.
- (2022). Broad-Spectrum Antivirals and Antiviral Drug Combinations. Viruses.
- (2022). Broad-Spectrum Antivirals and Antiviral Combinations: An Editorial Update. Viruses.
- (2021). DNA Damage Response. Biomolecules.
- (2021). DNA Damage Response. Biomolecules. 1-3.
- (2023). The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses.
- (2023). Genetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis. Viruses.
- (2023). Efficacy of interferon alpha for the treatment of hospitalized patients with COVID-19: A meta-analysis. Frontiers in Immunology. 8 sider.
- (2022). Weil’s Disease — Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota. Biomolecules. 1-17.
- (2022). Seven classes of antiviral agents. Cellular and Molecular Life Sciences (CMLS).
- (2022). Mono- and combinational drug therapies for global viral pandemic preparedness. iScience.
- (2022). Immunoregulatory Intestinal Microbiota and COVID-19 in Patients with Type Two Diabetes: A Double-Edged Sword. Viruses. 1-21.
- (2020). Interaction between Fibroblasts and Immune Cells Following DNA Damage Induced by Ionizing Radiation . International Journal of Molecular Sciences. 1-15.
- (2020). Genetic interaction between the non‐homologous end joining factors during B and T lymphocyte development: in vivo mouse models. Scandinavian Journal of Immunology. 1-9.
- (2020). Discovery and development of safe-in-man broad-spectrum antiviral agents. International Journal of Infectious Diseases. 268-276.