Background and activities

Education, training, experience

Research interests

We are working to determine how mutations in DNA repair genes result in disease

DNA in our cells is constantly damaged by 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 DNA 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 various cancers.

NHEJ includes core factors Ku70, Ku80, XLF, XRCC4 and Ligase 4. There are also accessory factors such as DNA-PKcs, Artemis, XLS/PAXX, APLF, Mri/Cyren. We are looking for new NHEJ factors as well. There is 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). 

In response to DNA damage, there is a complex process that includes the activation of multiple enzymes and modifications of proteins, including the histones surrounding the DSBs. This process is called the DNA damage response (DDR) pathway. It includes 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 (Nature, 2011; PNAS, 2012a; PNAS, 2012b; PLoS Genetics, 2013; DNA repair, 2014; DNA repair, 2017). We are attempting to understand the complexity of DDR, as well as its role in the development of immune and nervous systems, 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 (Nature, 2011; PNAS, 2012a, 2012b, 2013; DNA repair, 2014, 2017, 2019; FEBS open bio, 2018a, 2018b).

Translocations associated with V(D)J recombination and CSR can be detected using High Throughput Genome-Wide Translocation sequencing (HTGTS). We are working to develop blood cancer diagnostics using the HTGTS approach.

Projects

Projects in my group are funded by Young Research Talent grant from Research Council of Norway, Norwegian Cancer Society and the joined program of the Health Authority of Central Norway - NTNU.

We are working on the following projects:

Grants, Fellowships and Awards

  • 2019-2022:  Ph.D. candidate project funded by NTNU (enabling technology/Biotechnology)
  • 2018-2019:  PES and POS grants, NTNU, Norway
  • 2018-2019:  Fripro grant, The Research Council of Norway, Norway
  • 2016-2018:  Fripro grant, The Research Council of Norway, Norway
  • 2017-2020:  Norwegian Cancer Society Grant, Norway
  • 2017-2021:  NTNU Outstanding Academic Fellows Programme, Norway
  • 2016-2019:  Young Talent The Research Council of Norway grant, Norway
  • 2016-2018:  Health Authority of Central Norway grant (HMN-NTNU), Norway
  • 2015-2017:  Lundbeck Foundation Research Grant, Denmark
  • 2009:  Ph.D. student Fellowship, Cancer Research Association, France
  • 2008:  Ph.D. student Fellowship, Cancer Research Association, France

Research group

Currently, my team includes

  • Valentyn Oksenych, PhD, Researcher
  • Carole Beck, PhD, Postdoc
  • Sergio Miguel Castaneda Zegarra, Master student (external - Bergen University, 2019)
  • Qindong Zhang, MSc student (Molecular Medicine, 2019-2020)
  • Amin Alirezaylavasani, MSc student (Molecular Medicine, 2019-2020)
  • Kalaiyarasi Ragunathan, MSc student (Molecular Medicine, 2019-2020)
  • Nikki Upfold, Research assistant

Alumni

  • Kimiko Teyama, Medical exchange student from Oita University, Japan (Currently: Oita University, Japan)
  • Alisa Dewan, MSc student, Molecular Medicine, NTNU (Project score A. Currently is employed at University of Oslo)
  • Siri Sæterstad, Master Student (Biotechnology, 2018; Project score A. Currently studies at NTNU)
  • Phong Chau, BSc, Master Student (Biotechnology, 2018; Project score A. Currently: is employed at NTNU)
  • Stefano Bradamante, BSc, Stuff Engineer (Currently is employed at IKOM, NTNU)
  • Raquel Gago-Fuentes, PhD, Postdoc (Currently is employed at NTNU)
  • Camilla Huse, Master student (Molecular Medicine, 2019, final grade A). Currently employed at the University of Oslo.
  • Øystein Røsand, Master student (Molecular Medicine, 2019)
  • Mengtan Xing, MSc, PhD candidate. Currently postdoc at University of Oslo

Invited presentations and lectures

  • The Medical University of Innsbruck, Austria, 2019
  • First Immunology and Inflammation meeting, MDC, Berlin, 2019
  • University of Helsinki, 2019
  • University of Tartu, 2018
  • Oslo University, 2018
  • Karolinska Institutet, 2018
  • 2017: NTNU-KAIST Symposium "Molecular mechanisms underlying carcinogenesis and neurodegeneration", Trondheim, Norway
  • 2017: DNA and RNA dynamics workshop, Trondheim, Norway (organizer, chairman, speaker)
  • 2017: Norwegian Biochemical Society meeting, Oppdale, Norway
  • 2017: Norwegian Biochemical Society meeting, Gol, Norway
  • 2016: Symposium "DNA repair, Epigenetics and Translational medicine", Trondheim, Norway
  • 2016: European Commission, final interview of ERC starting grant, Brussels, Belgium
  • 2016: Norwegian Biochemical Society meeting, Åre, Sweden
  • 2016: Helsinki University, Biomedicum Helsinki Seminar, Finland
  • 2016: Norwegian Biochemical Society Annual Meeting, Tromsø, Norway
  • 2016: NTNU, Trondheim, Norway
  • 2015: Tomas Lindahl conference on DNA Repair, Oslo, Norway

Tips for grad students:

http://matt.might.net/articles/grad-student-resolutions/

Selected publications

ORCID orcid.org/0000-0002-5088-3791

The full list of publications can be found at:

Xing M, Oksenych V (2019). Genetic interaction between DNA repair factors PAXX, XLF, XRCC4 and DNA-PKcs in human cells. FEBS Open Bio. doi: 10.1002/2211-5463.12681

Castañeda-Zegarra S, Xing M, Gago-Fuentes R, Sæterstad S, Oksenych V. (2019). Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53. DNA repair (Amst.) 73:164-169.

Dewan A, Xing M, Lundbæk MB, Gago‐Fuentes R, Beck C, Aas PA, Liabakk NB, Sæterstad S, Phong C, Kavli B, Oksenych V. (2018). Robust DNA repair in PAXX‐deficient mammalian cells. FEBS Open Bio

Gago‐Fuentes R, Xing M, Sæterstad S, Sarno A, Dewan A, Beck C, Bradamante S, Bjørås M, Oksenych V. (2018). Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF. FEBS Open Bio

Xing M, Bjørås M, Daniel JA, Alt FW, Oksenych V. (2017) Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70. DNA Repair (Amst.) 57: 133-138

Bulanova D et al. (2017) Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins. Viruses 9(10). pii: E271

Kumar V, Alt FW, Oksenych V.* (2014) Functional overlaps between XLF and the ATM-dependent DNA double strand break response**. DNA Repair (Amst.) 16:11-22

Oksenych V, Zhovmer A, Ziani S, Mari PO, Eberova J, Nardo T, Stefanini M, Giglia-Mari G, Egly JM, Coin F. (2013) Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack. PLoS Genet 9(7):e1003611

Oksenych V, Kumar V, Liu X, Guo C, Schwer B, Zha S, Alt FW. (2013) Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining. Proc Natl Acad Sci USA 110(6):2234-9

Oksenych V, Alt FW, Kumar V, Schwer B, Wesemann DR, Hansen E, Patel H, Su A, Guo C. (2012) Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair. Proc Natl Acad Sci USA 109(7):2455-60

Boboila C*, Oksenych V*, Gostissa M, Wang JH, Zha S, Zhang Y, Chai H, Lee CS, Jankovic M, Saez LMA, Nussenzweig MC, McKinnon PJ, Alt FW, Schwer B.* (2012) Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1). Proc Natl Acad Sci USA 109(7):2473-8

Zha S, Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann DR, Yuen G, Patel H, Goff PH, Dubois RL, Alt FW. (2011) ATM Damage Response and XLF Repair Factor are Functionally Redundant In Joining DNA Breaks. Nature 469(7329):250-4

Zhovmer A, Oksenych V, Coin F. Two sides of the same coin: TFIIH complexes in transcription and DNA repair (2010) ScientificWorldJournal 10:633-43

Oksenych V, Coin F. (2010) The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell Cycle 9(1):90-6

Oksenych V, De Jesus BB, Zhovmer A, Egly JM, Coin F. (2009) Molecular insights into the recruitment of TFIIH to sites of DNA damage. EMBO J 28(19):2971-80

Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM. (2008) Nucleotide excision repair driven by the dissociation of CAK from TFIIH. Mol Cell 31(1):9-20

Coin F, Oksenych V, Egly JM. (2007) Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair. Mol Cell 26(2):245-56

Scientific, academic and artistic work

Displaying a selection of activities. See all publications in the database

Others

  • 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. Norwegian Biochemical Society 55th Contact Meeting . Norwegian Biochemical Society; Røros. 2019-01-24 - 2019-01-27.