Welcome to the Radiation Biology and DNA Damage Signaling group.
Our group focuses on DNA damage checkpoints in response to ionizing radiation and hypoxia. The main goals are to make novel discoveries regarding mechanisms of checkpoint signaling, and to contribute with new ideas for how such knowledge can be used to improve cancer therapy.
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 checkpoint signaling, in addition to more applied projects to understand how inhibitors of checkpoint signaling can be used in an optimized manner for cancer treatment.
• 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.
• The functional role of Protein phosphatase 1 (PP1) targeting subunits in regulation of checkpoint signaling after radiation.
• Identification of novel DNA damage combination treatments by flow cytometry-based large-scale compound screens.
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 (2010-2016):
1. 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
2. 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
3. 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.
4. 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.
5. 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.
6. 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.
7. 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 Res, 43 (22), e150, 2015.
8. R.G. Syljuåsen, G. Hasvold, S. Hauge, Å. Helland. Targeting lung cancer through inhibition of checkpoint kinases. Front Genet, 6, 70, 2015.
9. 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, In press, 2016.
Early phase drug development: From idea to concept
Feb 3, 2017
Feb 2, 2017
Oncolytic peptide LTX-315; the road from basic science to clinical trials
Jan 26, 2017
Randi Syljuåsen's group
Correction: MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features
Oncotarget, 8 (4), 7208-7213
MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features
Oncotarget, 7 (26), 40297-40313