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Natalia Isaeva, PhD

Assistant Professor

Specialty:

Head and neck cancer, HPV-associated malignancies.

Education:

  • M.Sc.,Novosibirsk State University, Novosibirsk, Russia (Biology), 1997
  • Ph.D., Karolinska Institute, Stockholm, Sweden (Cell and Tumor Biology), 2005
  • Postdoctoral Associate, Department of Genetics Microbiology and Toxicology (GMT), Stockholm University, Sweden, 2005-2009
  • Postdoctoral Associate, Department of Radiation Oncology, University of Michigan, MI, USA, 2009-2010

Professional Experience:

  • Assistant Professor, Department of Otolaryngology/Head and Neck Surgery, UNC-Chapel Hill, Chapel Hill, NC, 2018 – Present
  • Assistant Professor, Department of Surgery, Otolaryngology, Yale University, New Haven, CT,  2012 – 2018
  • Research Scientist, Department of Otolaryngology, Vanderbilt University, Nashville, TN, 2010 – 2012
  • Postdoctoral Associate, Department of Radiation Oncology, University of Michigan, MI, USA, 2009-2010
  • Postdoctoral Associate, Department of Genetics Microbiology and Toxicology (GMT), Stockholm University, Sweden, 2005-2009
  • Ph.D Student, Department of Oncology-Pathology; Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden, 2001 – 2005
  • Junior Scientist, Research Scientist, Laboratory of Oncogenesis and Laboratory of Morphology and Function of Cell Structures, Institute of Cytology and Genetics, Novosibirsk, Russia, 1998 – 2001

Recent Publications:

  • C Pan, N Issaeva*, WG Yarbrough*. HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis. Cancers of the Head & Neck 3 (1), 12, https://doi.org/10.1186/s41199-018-0039-3.
  • Lee JW, Parameswaran J, Sandoval-Schaefer T, Eoh KJ, Yang DH, Zhu F, Mehra R, Sharma R, Gaffney SG, Perry EB, Townsend JP, Serebriiskii IG, Golemis EA, Issaeva N, Yarbrough WG, Koo JS, Burtness BA. Combined Aurora kinase A (AURKA) and WEE1 inhibition demonstrates synergistic antitumor effect in squamous cell carcinoma of the head and neck.Clin Cancer Res. 2019 Feb 12. pii: clincanres.0440.2018. doi: 10.1158/1078-0432.CCR-18-0440. [Epub ahead of print]. PMID:30755439
  • Cheng H, Yang X, Si H, Saleh AD, Xiao W, Coupar J, Gollin SM, Ferris RL, Issaeva N, Yarbrough WG, Prince ME, Carey TE, Van Waes C, Chen Z. Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers. Cell Rep. 2018 Oct 30;25(5):1332-1345.e5. doi: 10.1016/j.celrep.2018.10.007.PMID:30380422.
  • Zhang J, Chen T, Yang X, Cheng H, Späth SS, Clavijo PE, Chen J, Silvin C, Issaeva N, Su X, Yarbrough WG, Annunziata CM, Chen Z, Van Waes C.Attenuated TRAF3 Fosters Activation of Alternative NF-κB and Reduced Expression of Antiviral Interferon, TP53, and RB to Promote HPV-Positive Head and Neck Cancers.Cancer Res. 2018 Jun 19. pii: canres.0642.2017. doi: 10.1158/0008-5472.CAN-17-0642. [Epub ahead of print] PMID: 29921694
  • Cannataro, VL; Gaffney, SG; Sasaki, T; Issaeva, N; Grewal, NKS; Grandis, JR; Yarbrough, WG; Burtness, BA; Anderson, KS; and Townsend, JP. APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma. Oncogene, 2019 Jan 15. doi: 10.1038/s41388-018-0657-6.
  • Natalia Issaeva, Barbara Burtness and Wendell G. Yarbrough. TRAF3 and CYLD Gene Defects in HPV-Associated Head and Neck Cancer: Biomarker of Response and Indicator of Targets for New Therapies. J Cancer Clin Trials 2018, Volume 3 • Issue 1 • 142.
  • Biktasova AK, Hajek M, Sewell AB, Gary CS, Bellinger G, Deshpande H, Bhatia AK, Burtness BA, Judson BL, Mehra S, Yarbrough WG, Issaeva N. “Demethylation therapy as a targeted treatment for human papilloma virus-associated head and neck cancer”. Clin Cancer Res. 2017 Dec 1;23(23):7276-7287. doi: 10.1158/1078-0432.CCR-17-1438. PMID:29196570.
  • 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; 123(10):1778-1790. NIHMSID: NIHMS840954 PubMed [journal] PMID: 28295222, PMCID: PMC5419871.
  • Wamsley JJ*, Gary C*, Biktasova A, Hajek M, Bellinger G, Virk R, Issaeva N*, Yarbrough WG*. Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Oncogenesis. 2017; 6(4):e314. PubMed[journal] PMID: 28394357.
  • 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 (Georgetown, Tex.). 2017; 16(2):213-223. PubMed [journal] PMID:28027003, PMCID: PMC5283812.
  • Gary C*, Hajek M*, Biktasova A, Bellinger G, Yarbrough WG, Issaeva N.Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget. 2016; 7(25):38598-38611. PubMed [journal] PMID: 27233076, PMCID: PMC5122414.
  • 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; 38 Suppl 1:E1381-91. PubMed [journal] 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 (Georgetown, Tex.). 2016; 15(3):455-70. PubMed [journal] PMID: 26694952, PMCID: PMC4943693
  • 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. Science translational medicine. 2015; 7(312):312ra176. PubMed [journal] 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. Characterization of HPV and host genome interactions in primary head and neck cancers. Proceedings of the National Academy of Sciences of the United States of  2014; 111(43):15544-9. PubMed [journal] PMID: 25313082, PMCID: PMC4217452.
  • Sewell A, Brown B, Biktasova A, Mills GB, Lu Y, Tyson DR, Issaeva N*, Yarbrough WG*.Reverse-phase protein array profiling of oropharyngeal cancer andsignificance of PIK3CA mutations in HPV-associated head and neck cancer. Clinicalcancer research : an official journal of the American Association for Cancer 2014; 20(9):2300-11. NIHMSID: NIHMS572822 PubMed [journal] PMID:24599934, PMCID: PMC4027970.
  • Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J, Eriksson S, Hedström E, Issaeva N, Kel A, Arnér ES, Selivanova G. ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell death and differentiation. 2014; 21(4):612-23. PubMed [journal] PMID: 24413150, PMCID: PMC3950324.
  • 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 (Georgetown, Tex.). 2013; 12(24):3770-80. PubMed [journal] PMID: 24107632, PMCID: PMC3905069.
  • Ivanov SV, Panaccione A, Brown B, Guo Y, Moskaluk CA, Wick MJ, Brown JL, Ivanova AV, Issaeva N, El-Naggar AK, Yarbrough WG. TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior. Oncogene. 2013; 32(32):3698-710. PubMed [journal] PMID: 230271301.
  • Uzhachenko R, Issaeva N, Boyd K, Ivanov SV, Carbone DP, Ivanova AV. Tumour suppressor Fus1 provides a molecular link between inflammatory response and mitochondrial homeostasis. The Journal of pathology. 2012; 227(4):456-69. PubMed [journal] PMID: 22513871.
  • 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(5):1257-67. NIHMSID: NIHMS519228 PubMed [journal] PMID: 22247495, PMCID:PMC4010255.
  • Liu D, Wang WD, Melville DB, Cha YI, Yin Z, Issaeva N, Knapik EW, Yarbrough WG. Tumor suppressor Lzap regulates cell cycle progression, doming, and zebrafish epiboly. Developmental dynamics : an official publication of the American Association of Anatomists. 2011; 240(6):1613-25. NIHMSID: NIHMS352693 PubMed [journal] PMID: 21523853, PMCID: PMC3287344.
  • Bao W, Chen M, Zhao X, Kumar R, Spinnler C, Thullberg M, Issaeva N, Selivanova G, Strömblad S. PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivo. Cell cycle (Georgetown, Tex.). 2011; 10(2):301-7. PubMed [journal] PMID: 21239882.
  • 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(15):6268-76. NIHMSID: UKMS31228 PubMed [journal] PMID: 20631063, PMCID: PMC2913123.

Chapters and Books:

  •  Tomoaki Sasaki, Natalia Issaeva, Wendell G. Yarbrough, Karen S. Anderson. APOBEC as an Endogenous Mutagen in Cancers of the Head and Neck. Molecular Determinants of Head and Neck Cancer Second Edition, pp 275-292, Print ISBN 978-3-319-78761-9; Online ISBN 978-3-319-78762-6.
  •  Ryan Aronberg, Natalia Issaevaand Wendell G. Yarbrough. Cancer of the Head and Neck 5th Chapter 2 – Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck.  Philadelphia: Wolters Kluwer, [2017], pp 4-29. Identifiers: LCCN 2016015692 | ISBN 9781451191134 Subjects: | MESH: Head and Neck Neoplasms Classification: LCC RC280.H4 | NLM WE 707 | DDC 616.99/491—dc23 LC record available at https://lccn.loc.gov/2016015692
  •  Natalia Issaevaand Wendell G. Yarbrough. 11th Edition of Essential Otolaryngology-Head and Neck Surgery. Chapter – Tumor Biology and Genetics of Head & Neck Tumors. McGraw-Hill Education / Medical; 11 edition (October 9, 2015), ISBN-10: 0071849920, ISBN-13: 978-0071849920

Editorial:

  • Cassie Pan, Wendell G. Yarbrough and Natalia Issaeva. Advances in  biomarkers   and treatment   strategies  for HPV-associated head and neck cancer. Oncoscience. 2018 Jun 25;5(5-6):140-141. doi: 10.18632/oncoscience.425. eCollection 2018 May.
  • Issaeva N.P53 Signaling in Cancers. Cancers (Basel). 2019 Mar 8;11(3). pii: E332. doi: 3390/cancers11030332.3