DNA in our cells is constantly damaged by various internal and external factors. To maintain genomic stability, the cells developed 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 the 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 (e.g., 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., 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.
2020-Now Researcher. University of Oslo, Norway
2020: Researcher. University of Tromsø, Norway
2018-2020 Research visit. Karolinska Institutet, Sweden
2015-2020 Researcher, principal investigator. NTNU - Trondheim, Norway
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 Stiftelser och Fonder)
2020-2021 Health Authority of Central Norway
2019-2022 PhD position (SO), award in innovation, NTNU, Norway
2018-2019 NTNU PES and POS grants, Norway
2018-2019 Research Council of Norway, FRIPRO
2017-2021 Outstanding Academic Fellow Award, NTNU, Norway
2017-2020 Norwegian Cancer Society, Open call
2016-2019 Research Council of Norway, FRIMEDBIO
2016-2018 Research Council of Norway, FRIPRO
2016-2018 Health Authority of Central Norway
2015-2017 Lundbeck Fellowship, University of Copenhagen, Denmark
2009 Anti-Cancer Research Association (ARC), France
2008 Anti-Cancer Research Association (ARC), France
2005 Mobility grant, IBB - Academy of Science, Warsaw, Poland