DNA Repair; DNA Replication; Head and Neck Neoplasms; Oncogenes; Otolaryngology; Genes, Tumor Suppressor; Tumor Suppressor Protein p53; Human papillomavirus 11
Our long term research interest is to improve cancer treatment by targeting specific cancer defects.
Currently we are working on:
1. Association between human papilloma virus and the development of head and neck cancer.
2. Link between human papilloma virus and DNA damage signaling and repair in head and neck cancer.
3. Cellular and small molecules modulators of p53 expression and functions;
4. Designing of novel therapeutic strategies to target specific tumors exploiting their various defects.
Specialized Terms: Oncogenes and tumor suppressors; DNA replication and repair; P53 regulation and signaling; Head and neck cancer; Human papilloma virus
- Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival. Evgenia Gubanova, Brandee Brown, Sergei V. Ivanov, Thomas Helleday, Wendell G. Yarbrough and Natalia Issaeva. Clin. Cancer Res. 2012 Mar 1; 18(5):1257-1267.
- Natalia Issaeva, Huw D. Thomas, Tatjana Djurenovic, Janneke E. Jaspers, Ivaylo Stoimenov, Suzanne Kyle, Nicholas Pedley, Ponnari Gottipati, Rafal Zur, Kate Sleeth, Vicky Chatzakos, Evan Mulligan, Cecilia Lundin, Evgenia Gubanova, Ariena Kersbergen, Adrian L. Harris, Ricky A. Sharma, Sven Rottenberg, Nicola J. Curtin, and Thomas Helleday. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res. 2010 Aug 1;70(15):6268-76.
- Eva Petermann, Manuel Lui´s Orta, Natalia Issaeva, Niklas Schultz, and Thomas Helleday. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol Cell, 2010 Feb
- Bryant HE, Petermann E, Schultz N, Jemth AS, Loseva O, Issaeva N, Johansson F, Fernandez S, McGlynn P, Helleday T. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J, 2009 Sep 2;28(17):2601-15.
- Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Orntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, Gorgoulis VG. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature, 2006 Nov 30; 444(7119):633-7.
- V.Bykov, N.Issaeva, N.Zache, A.Shilov, M.Hultcrantz, J.Bergman, G.Selivanova, K.G.Wiman. Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs. J Biol Che,. 2005 Aug 26;280(34):30384-91.
- Natalia Issaeva, Przemyslaw Bozko, Martin Enge, Marina Protopopova, Lisette G.G.C. Verhoef, Maria Masucci, Aladdin Pramanik, and Galina Selivanova. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nature Medicine 2004, Dec;10(12):1321-8.
- Natalia Issaeva#, Assaf Friedler#, Przemyslaw Bozko, Klas G. Wiman, Alan R. Ferst* and Galina Selivanova*. Rescue of mutants of the tumour suppressor p53 in cancer cells by a designed peptide. PNAS, 2003 Nov 11;100(23):13303-7.
- V.Bykov, N.Issaeva, A.Shilov, M.Hultcrantz, E.Pugacheva, P.Chumakov, J.Bergman, K.G.Wiman, and G. Selivanova. Restoration of the Tumor Suppressor Function to Mutant p53 by a Low Molecular Weight Compound. Nature Medicine, March 2002, 8(3):282-288.