Valentyn Oksenych

Academic interests

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. 

Background

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