Welcome to the Radiation Biology and DNA Damage Signaling group.

Our goal is to obtain new knowledge about cellular responses to radiation and utilize it to improve cancer therapy. The group focuses on DNA damage checkpoints and repair in response to ionizing radiation. 

In radiotherapy ionizing radiation is used to cause DNA damage in cancer cells. The DNA damage is rapidly sensed and a network of intracellular DNA damage signaling cascades is activated. These signaling cascades influence whether the cells die or survive, through regulation of DNA repair, cell cycle checkpoint and cell death pathways. Our group works on the border between basic and translational radiation research. We conduct basic projects to identify novel mechanisms of DNA damage signaling, in addition to more applied projects to understand how inhibitors of checkpoints and repair can be used in an optimized manner for cancer treatment.

Ongoing projects:

  • Pre-clinical exploration of checkpoint kinase inhibitors (Chk1, Wee1, Atr) as a strategy for cancer treatment in normoxic and hypoxic cancer cells in the absence and presence of ionizing radiation.
  • Identification of drugs that inhibit DNA repair after radiation, by flow cytometry-based large-scale compound screens.
  • The functional role of Protein phosphatase 1 (PP1) targeting subunits in regulation of checkpoint and repair signaling .
  • Links between DNA damage signaling and anti-tumor immune responses after radiation.

Methods:

We study human cancer and normal cell lines and use many different techniques including immunofluorescence microscopy and live cell imaging, multiparameter flow cytometry, immunoblotting, immunoprecipitation, protein overexpression, siRNA transfection, hypoxia treatment, X-ray irradiation, and robot-automated flow cytometry large-scale screening.

Selected group publications (2010-2019):
1. H.B. Landsverk, L.E. Sandquist, S.C. Sridhara, G.E. Rødland, J.C. Sabino, S.F. de Almeida, B. Grallert, L. Trinkle-Mulcahy, R.G. Syljuåsen.Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1. Nucleic Acids Research, 47, p.1797-1813, 2019.

2. S. Hauge, C. Naucke, G. Hasvold, M. Joel, G.E. Rødland, P. Juzenas, T. Stokke, R.G. Syljuåsen. Combined inhibition of Wee1 and Chk1 gives synergistic DNA damage in S-phase due to distinct regulation of CDK activity and CDC45 loading. Oncotarget, 8, p.10966-10979, 2017.

3. G. Hasvold, C. Lund-Andersen, M. Lando, S. Patzke, S. Hauge, Z-H. Suo, H. Lyng, R.G. Syljuåsen. Hypoxia-induced alterations of G2 checkpoint regulators. Molecular Oncology, 10, p. 764-73, 2016.

4. T.W. Håland, E. Boye, T. Stokke, B. Grallert, R.G. Syljuåsen. Simultaneous measurement of passage through the restriction point and MCM loading in single cells. Nucleic Acids Research, 43, p.e150, 2015.

5. C. Lund-Andersen, S. Patzke, V. Nähse-Kumpf, R.G. Syljuåsen. Plk1-inhibition can cause radiosensitization or radioresistance dependent on the treatment schedule. Radiation Therapy and Oncology, 110, p.355-361, 2014.

6. G. Hasvold, V. Nähse-Kumpf, K. Tkacz-Stachowska, E. Rofstad, R.G. Syljuåsen. The efficacy of CHK1-inhibitors is not altered by hypoxia, but is enhanced after reoxygenation. Molecular Cancer Therapeutics, 12, 705-716, 2013.

7. H.Beck1,V. Nähse-Kumpf1, M.S Yoo Larsen, S. Patzke, C. Holmberg, O. Nielsen, R.G. Syljuåsen*, C.S. Sørensen*. CDK suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell. Biol., 32, 4226-36, 2012. 1Equal contribution. *Shared corresponding authorship.

8. C.S. Sørensen and R.G. Syljuåsen. Safeguarding genome integrity: The checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication. Nucleic Acids Research, 40, p.477-486, 2012.

9. T. Menzel, V. Nähse-Kumpf, A. Nedergaard Kousholt, D. Kjærsgaard Klein, C. Lund-Andersen, M. Lees, J. Vilstrup Johansen, R.G. Syljuåsen*, C.S. Sørensen*. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance. EMBO Reports, 12, p.705-712, 2011. *Shared corresponding authorship.

10. H.B. Landsverk, F. Mora-Bermudez, O.J.B. Landsverk, G. Hasvold, S. Naderi, O. Bakke, J. Ellenberg, P. Collas, R.G. Syljuåsen*, T. Küntziger*. The protein phosphatase 1 regulator PNUTS is a new component of the DNA damage response. EMBO Reports, 11, 868-75, 2010. *shared corresponding authorship

 

Contact information:

Randi G. Syljuåsen, Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital. Phone: +47 22781468. email: randi.syljuasen@rr-research.no