Valentyn Oksenych

Bilde av Valentyn Oksenych
English version of this page
Brukernavn
Besøksadresse Sognsvannsveien 20 Rikshospitalet 0372 Oslo
Postadresse OUS HF Rikshospitalet Postboks 4950 Nydalen 0424 Oslo

Academic interests

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 human. 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 (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 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

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

Emneord: B cells, DNA repair, mouse models, Genetics, Immunology

Publikasjoner

  • Andersen, Petter I.; Ianevski, Aleksandr; Lysvand, Hilde; Vitkauskiene, Astra; Oksenych, Valentyn; Bjørås, Magnar; Telling, Kaidi; Lutsar, Irja; Dumpis, Uga; Irie, Yasuhiko; Tenson, Tanel; Kantele, Anu & Kainov, Denis (2020). Discovery and development of safe-in-man broad-spectrum antiviral agents. International Journal of Infectious Diseases.  ISSN 1201-9712.  93, s 268- 276 . doi: 10.1016/j.ijid.2020.02.018
  • Beck, Carole; Castaneda Zegarra, Sergio Miguel; Huse, Camilla; Xing, Mengtan & Oksenych, Valentyn (2020). Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF. Biomolecules.  ISSN 2218-273X.  10(60) . doi: 10.3390/biom10010060 Fulltekst i vitenarkiv.
  • Castaneda Zegarra, Sergio Miguel; Fernandez Berrocal, Marion Silvana; Tkachev, Max; Yao, Rouan; Esnardo Upfold, Nikki Lyn & Oksenych, Valentyn (2020). Genetic interaction between the non‐homologous end joining factors during B and T lymphocyte development: in vivo mouse models. Scandinavian Journal of Immunology.  ISSN 0300-9475.  92:e12936(4), s 1- 9 . doi: 10.1111/sji.12936
  • Castaneda Zegarra, Sergio Miguel; Zhang, Qindong; Alirezaylavasani, Amin; Fernandez-Berrocal, Marion Silvana; Yao, Rouan & Oksenych, Valentyn (2020). Leaky severe combined immunodeficiency in mice lacking non-homologous end joining factors XLF and MRI. Aging.  ISSN 1945-4589.  12(23), s 23578- 23597 . doi: 10.18632/aging.202346 Vis sammendrag
  • Castañeda-Zegarra, Sergio; Zhang, Qindong; Alirezaylavasani, Amin; Fernandez Berrocal, Marion; Yao, Rouan & Oksenych, Valentyn (2020). Leaky severe combined immunodeficiency in mice lacking non-homologous end joining factors XLF and MRI. Aging.  ISSN 1945-4589.  12(Advance) . doi: 10.18632/aging.202346
  • Gago-Fuentes, Raquel & Oksenych, Valentyn (2020). Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population. Biomolecules.  ISSN 2218-273X.  11:20(1), s 1- 13 . doi: 10.3390/biom11010020
  • Ianevski, Aleksandr; Kulesskiy, Evgeny; Krpina, Klara; Lou, Guofeng; Aman, Yahyah; Bugai, Andrii; Aasumets, Koit; Akimov, Yevhen; Bulanova, Daria; Gildemann, Kiira; Arutyunyan, Albert F.; Susova, Olga Yu.; Zhuze, Alexei L.; Ji, Ping; Wang, Wei; Holien, Toril; Bugge, Marit; Zusinaite, Eva; Oksenych, Valentyn; Lysvand, Hilde; Gerhold, Joachim M.; Bjørås, Magnar; Johansen, Pål; Waage, Anders; Heckman, Caroline A.; Fang, Fei & Kainov, Denis (2020). Chemical, Physical and Biological Triggers of Evolutionary Sonserved Bcl-xL-Mediated Apoptosis. Cancers.  ISSN 2072-6694.  12(6), s 1- 19 . doi: 10.3390/cancers12061694
  • Ianevski, Aleksandr; Yao, Rouan; Fenstad, Mona H.; Biza, Svetlana; Zusinaite, Eva; Reisberg, Tuuli; Lysvand, Hilde; Løseth, Kirsti; Landsem, Veslemøy Malm; Fossum, Janne; Erlandsen, Sten Even; Aas, Per Arne; Hagen, Lars; Pettersen, Caroline Hild; Tenson, Tanel; Afset, Jan Egil; Nordbø, Svein Arne; Bjørås, Magnar; Kainov, Denis & Oksenych, Valentyn (2020). Potential Antiviral Options against SARS-CoV-2 Infection. Viruses.. Viruses.  ISSN 1999-4915.  s E642 . doi: 10.3390/v12060642
  • Ragunathan, Kalaiyarasi; Esnardo Upfold, Nikki Lyn & Oksenych, Valentyn (2020). Interaction between Fibroblasts and Immune Cells Following DNA Damage Induced by Ionizing Radiation. International Journal of Molecular Sciences.  ISSN 1422-0067.  21:8635(22), s 1- 15 . doi: 10.3390/ijms21228635 Fulltekst i vitenarkiv.
  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Anderssen, Petter Inge; Kuivanen, Suvi; Teppor, Mona; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca Jane; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit Walbye; Shum, David H.K.; Kaarbø, Mari; Vapalahti, Olli; Windisch, Marc P.; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis & Kandasamy, Richard Kumaran (2019). Common nodes of virus-host interaction revealed through an integrated network analysis. Frontiers in Immunology.  ISSN 1664-3224.  10 . doi: 10.3389/fimmu.2019.02186 Fulltekst i vitenarkiv.
  • Castaneda Zegarra, Sergio Miguel; Huse, Camilla; Røsand, Øystein; Sarno, Antonio; Xing, Mengtan; Gago-Fuentes, Raquel; Zhang, Qindong; Alirezaylavasani, Amin; Werner, Julia; Ji, Ping; Liabakk, Nina-Beate; Wang, Wei; Bjørås, Magnar & Oksenych, Valentyn (2019). Generation of a mouse model lacking the non-homologous end-joining factor Mri/Cyren. Biomolecules.  ISSN 2218-273X.  9:798(12), s 1- 13 . doi: 10.3390/biom9120798 Fulltekst i vitenarkiv. Vis sammendrag
  • Castaneda Zegarra, Sergio Miguel; Xing, Mengtan; Gago-Fuentes, Raquel; Sæterstad, Siri & Oksenych, Valentyn (2019). Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53. DNA Repair.  ISSN 1568-7864.  73, s 164- 169 . doi: 10.1016/j.dnarep.2018.12.002 Fulltekst i vitenarkiv.
  • Ianevski, Aleksandr; Zusinaite, Eva; Shtaida, Nastassia; Kallio-Kokko, Hannimari; Valkonen, Mia; Kantele, Anu; Telling, Kaidi; Lutsar, Irja; Letjuka, Pille; Metelitsa, Natalja; Oksenych, Valentyn; Dumpis, Uga; Vitkauskiene, Astra; Stašaitis, Kestutis; Öhrmalm, Christina; Bondeson, Kåre; Bergqvist, Anders; Cox, Rebecca Jane; Tenson, Tanel; Merits, Andres & Kainov, Denis (2019). Low temperature and low UV indexes correlated with peaks of influenza virus activity in Northern Europe during 2010-2018. Viruses.  ISSN 1999-4915.  11:207(3), s 1- 10 . doi: 10.3390/v11030207 Fulltekst i vitenarkiv.
  • Xing, Mengtan & Oksenych, Valentyn (2019). Genetic interaction between DNA repair factors PAXX, XLF, XRCC4 and DNA-PKcs in human cells. FEBS Open Bio.  ISSN 2211-5463.  9(7), s 1315- 1326 . doi: 10.1002/2211-5463.12681 Fulltekst i vitenarkiv.
  • Ianevski, Aleksandr; Zusinaite, Eva; Kuivanen, Suvi; Strand, Mårten; Lysvand, Hilde; Teppor, Mona; Kakkola, Laura; Paavilainen, Henrik; Laajala, Mira; Kallio-Kokko, Hannimari; Valkonen, Miia; Kantele, Anu; Telling, Kaidi; Lutsar, Irja; Letjuka, Pille; Metelitsa, Natalja; Oksenych, Valentyn; Bjørås, Magnar; Nordbø, Svein Arne; Dumpis, Uga; Vitkauskiene, Astra; Öhrmalm, Christina; Bondeson, Kåre; Bergqvist, Anders; Aittokallio, Tero; Cox, Rebecca Jane; Evander, Magnus; Hukkanen, Veijo; Marjomäki, Varpu; Julkunen, Ilkka; Vapalahti, Olli; Tenson, Tanel; Merits, Andres & Kainov, Denis (2018). Novel activities of safe-in-human broad-spectrum antiviral agents. Antiviral Research.  ISSN 0166-3542.  154, s 174- 182 . doi: 10.1016/j.antiviral.2018.04.016
  • Dewan, Alisa Elinsdatter; Xing, Mengtan; Lundbæk, Marie Benner; Gago-Fuentes, Raquel; Beck, Carole; Aas, Per Arne; Liabakk, Nina-Beate; Sæterstad, Siri; Chau, Khac Thanh Phong; Kavli, Bodil Merete & Oksenych, Valentyn (2018). Robust DNA repair in PAXX-deficient mammalian cells. FEBS Open Bio.  ISSN 2211-5463.  8(3), s 442- 448 . doi: 10.1002/2211-5463.12380 Fulltekst i vitenarkiv.
  • Gago-Fuentes, Raquel; Xing, Mengtan; Sæterstad, Siri; Sarno, Antonio; Dewan, Alisa Elinsdatter; Beck, Carole; Bradamante, Stefano; Bjørås, Magnar & Oksenych, Valentyn (2018). Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF. FEBS Open Bio.  ISSN 2211-5463.  8(3), s 426- 434 . doi: 10.1002/2211-5463.12381 Fulltekst i vitenarkiv.
  • Bulanova, Daria; Ianevski, Aleksandr; Bugai, Andrii; Akimov, Yevhen; Kuivanen, Suvi; Paavilainen, Henrik; Kakkola, Laura; Nandania, Jatin; Turunen, Laura; Ohman, Tiina; Ala-Hongisto, Hanna; Pesonen, Hanna M; Kuisma, Marika S; Honkimaa, Anni; Walton, Emma Louise; Oksenych, Valentyn; Lorey, Martina B.; Guschin, Dmitry; Shim, Jungmin; Kim, Jinhee; Than, Thoa T; Chang, So Young; Hukkanen, Veijo; Kulesskiy, Evgeny; Marjomaki, Varpu S; Julkunen, Ilkka; Nyman, Tuula Anneli; Matikainen, Sampsa; Saarela, Jani S; Sane, Famara; Hober, Didier; Gabriel, Gulsah; De Brabander, Jef K; Martikainen, Miika; Windisch, Marc P; Min, Ji-Young; Bruzzone, Roberto; Aittokallio, Tero; Vaha-Koskela, Markus; Vapalahti, Olli; Pulk, Arto; Velagapudi, Vidya & Kainov, Denis (2017). Antiviral properties of chemical inhibitors of cellular anti-apoptotic Bcl-2 proteins. Viruses.  ISSN 1999-4915.  9(10) . doi: 10.3390/v9100271 Fulltekst i vitenarkiv.
  • Xing, Mengtan; Bjørås, Magnar; Daniel, Jeremy A.; Alt, Frederick W. & Oksenych, Valentyn (2017). Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70. DNA Repair.  ISSN 1568-7864.  57, s 133- 138 . doi: 10.1016/j.dnarep.2017.07.008 Fulltekst i vitenarkiv.

Se alle arbeider i Cristin

  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Andersen, Petter I.; Kuivanen, Suvi; Mona, Teppor; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca J.; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit Walbye; Shum, David H.K.; Kaarbø, Mari; Vapalahti, Olli; Windisch, Marc P; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis & Kandasamy, Richard Kumaran (2019). Critical Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis.
  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Andersen, Petter I.; Teppor, Mona; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca Jane; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit Walbye; Shum, David H.K.; Kaarbø, Mari; Windisch, Marc P.; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis & Kandasamy, Richard Kumaran (2019). Critical Nodes of Viral Modulation Revealed Through an Integrated Network Analysis of Host-Virus Interaction Landscape.

Se alle arbeider i Cristin

Publisert 27. nov. 2020 14:17 - Sist endret 2. des. 2020 19:04