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.
Gubanova E, Brown B, Ivanov SV, Helleday T, Mills GB, Yarbrough WG, Issaeva N. Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival. Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research 2012, 18:1257-67.
6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.
Issaeva N, Thomas HD, Djureinovic T, Jaspers JE, Stoimenov I, Kyle S, Pedley N, Gottipati P, Zur R, Sleeth K, Chatzakos V, Mulligan EA, Lundin C, Gubanova E, Kersbergen A, Harris AL, Sharma RA, Rottenberg S, Curtin NJ, Helleday T. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Research 2010, 70:6268-76.
Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair.
Petermann E, Orta ML, Issaeva N, Schultz N, Helleday T. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Molecular Cell 2010, 37:492-502.
PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination.
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. The EMBO Journal 2009, 28:2601-15.
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints.
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, Ørntoft 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, 444:633-7.
Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs.
Bykov VJ, Issaeva N, Zache N, Shilov A, Hultcrantz M, Bergman J, Selivanova G, Wiman KG. Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs. The Journal Of Biological Chemistry 2005, 280:30384-91.
Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors.
Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nature Medicine 2004, 10:1321-8.
Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide.
Issaeva N, Friedler A, Bozko P, Wiman KG, Fersht AR, Selivanova G. Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100:13303-7.
Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.
Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG, Selivanova G. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nature Medicine 2002, 8:282-8.
Full List of PubMed Publications
- Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N: Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Clin Cancer Res. 2017 Dec 1; 2017 Sep 15. PMID: 28916527
- Hajek M, Sewell A, Kaech S, Burtness B, Yarbrough WG, Issaeva N: TRAF3/CYLD mutations identify a distinct subset of human papillomavirus-associated head and neck squamous cell carcinoma. Cancer. 2017 May 15; 2017 Mar 13. PMID: 28295222
- Wamsley JJ, Issaeva N, An H, Lu X, Donehower LA, Yarbrough WG: LZAP is a novel Wip1 binding partner and positive regulator of its phosphatase activity in vitro. Cell Cycle. 2017 Jan 17; 2016 Dec 27. PMID: 28027003
- Gary C, Hajek M, Biktasova A, Bellinger G, Yarbrough WG, Issaeva N: Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget. 2016 Jun 21. PMID: 27233076
- Sasaki CT, Issaeva N, Vageli DP: In vitro model for gastroduodenal reflux-induced nuclear factor-kappaB activation and its role in hypopharyngeal carcinogenesis. Head Neck. 2016 Apr; 2015 Nov 11. PMID: 26559497
- Fleyshman D, Cheney P, Ströse A, Mudambi S, Safina A, Commane M, Purmal A, Morgan K, Wang NJ, Gray J, Spellman PT, Issaeva N, Gurova K: ARTIK-52 induces replication-dependent DNA damage and p53 activation exclusively in cells of prostate and breast cancer origin. Cell Cycle. 2016; 2015 Dec 22. PMID: 26694952
- Carter DR, Murray J, Cheung BB, Gamble L, Koach J, Tsang J, Sutton S, Kalla H, Syed S, Gifford AJ, Issaeva N, Biktasova A, Atmadibrata B, Sun Y, Sokolowski N, Ling D, Kim PY, Webber H, Clark A, Ruhle M, Liu B, Oberthuer A, Fischer M, Byrne J, Saletta F, Thwe le M, Purmal A, Haderski G, Burkhart C, Speleman F, De Preter K, Beckers A, Ziegler DS, Liu T, Gurova KV, Gudkov AV, Norris MD, Haber M, Marshall GM: Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. Sci Transl Med. 2015 Nov 4. PMID: 26537256
- Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, Protopopov A, Yang L, Seth S, Song X, Tang J, Ren X, Zhang J, Pantazi A, Santoso N, Xu AW, Mahadeshwar H, Wheeler DA, Haddad RI, Jung J, Ojesina AI, Issaeva N, Yarbrough WG, Hayes DN, Grandis JR, El-Naggar AK, Meyerson M, Park PJ, Chin L, Seidman JG, Hammerman PS, Kucherlapati R, Cancer Genome Atlas Network.: Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci U S A. 2014 Oct 28; 2014 Oct 13. PMID: 25313082
- Sewell A, Brown B, Biktasova A, Mills GB, Lu Y, Tyson DR, Issaeva N, Yarbrough WG: Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-associated head and neck cancer. Clin Cancer Res. 2014 May 1; 2014 Mar 5. PMID: 24599934
- Gubanova E, Issaeva N, Gokturk C, Djureinovic T, Helleday T: SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A signaling pathways. Cell Cycle. 2013 Dec 15; 2013 Oct 4. PMID: 24107632