Professor and Vice-Chair

Director of Head and Neck Surgical Oncology and Research

Contact Information:
Email: cnatha@lsuhsc.edu
Office Phone: 318-675-6264
Office Fax: 318-675-6260

Education/Training:
Medical School - University of Bombay

Post-Doctoral Head and Neck Fellowship - Johns Hopkins

Residency - University of California-San Diego

Major Research Interests:  
Head and neck surgical oncology, Molecular markers in head and neck cancer, laryngology/voice disorders

The eukaryotic translation initiation factor eIF4E acts in the rate limiting step of translation initiation, first binding the 7-methyl guanosine (m7G) cap structure on mRNA and then recruiting transcripts to the ribosome.  Deregulation of eIF4E leads to oncogenic transformation due to the selective translation of growth promoting transcripts having highly structured 5’ untranslated regions (UTR).  Our laboratory has shown that eIF4E is overexpressed in head and neck tumors, with increased levels of eIF4E being correlated with poor clinical outcome.  Whereas cytoplasmic eIF4E functions to initiate cap-dependent translation, nuclear eIF4E promotes transport of mRNA subsets into the cytoplasm.  Both transport and oncogenic transformation activities of eIF4E are negatively regulated by the promyelocytic leukemia protein PML, which forms large multiprotein nuclear complexes (called ND10 or PML bodies) that include nuclear eIF4E.  Integrity of PML nuclear bodies is affected in a variety of pathologic conditions, foremost of which is acute promyelocytic leukemia where PML body disruption (consequent to a chromosomal translocation) can be effectively reversed by treatment and reassembly correlates with disease remission.  Dispersal of PML bodies frees bound eIF4E and increases eIF4E mediated mRNA transport and translation.  Because disruption of PML bodies is also seen with human virus infection, we hypothesize that oral reactivation of latent viral pathogens leads to an enhancement of eIF4E-dependent mRNA transport that may manifest as hyperplastic or proliferative diseases of the oral mucosa. We are collaborating with Dr.  Sixbey and Dr. Rona Scott’s laboratories, to study the impact of PML nuclear body disruption by Epstein-Barr virus (EBV) on eIF4E-dependent nucleocytoplasmic transport function in both an in vitro system and in patients with HNSCC.

Representative Publications:

1. Nathan CO, Amirghahari N, Rong X, Giordano A, Sibley D, Nordberg M, Glass J, Agarwal A, Caldito G. mTOR Inhibitors as possible adjuvant therapy for microscopic residual disease in head and neck squamous cell cancer. Cancer Res.; 67(5):2160-8, 2007.
2. DeBenedetti A, Mathis J, Williams J, Nathan CO. Cancer-specific Targeting of an Adenovirus-delivered Herpes Simples Virus Thymidine Kinase Suicide Gene Using Translational Control (accepted The Journal of Gene Medicine 2006)
3. Nathan CO, Amirghahari N, Rong X, Sibley D, Giordano A. Bioluminescence tracks the in vivo effects of CCI-779 in a Minimal Residual Disease Model of HNSCC. 97th Annual AACR Meeting proceedings Vol. 47, 1049: 2006.
4. Moody, CA, Scott RS, Amirghahari N, Nathan CO, Young LS, Dawson CW, Sixbey JW. Modulation of Cell Growth Regulator mTOR by Epstein-Barr Virus-Encoded LMP2A. J Virol. May; 79(9):5499-506, 2005.
5. Amirghahari N, Sibley D, Rong X, Caldito G, Nathan CO. Growth Inhibitory and pharmacodynamic effects of CCI-779, an mTOR inhibitor, in a preclinical microscopic residual disease model of head and neck squamous carcinoma. 96th Annual AACR Meeting proceedings Vol.46, pg107, 2005.
6. Nathan CO, Amirghahari N, Abreo F, Rong X, Caldito G, Jones ML, Zhou H, Smith M, Kimberly D, Glass J.  Overexpressed eIF4E is functionally active in surgical margins of head and neck cancer patients via activation of the Akt/mTOR pathway. Clinical Cancer Research; 10: 5820-5827, 2004.
7. Nathan CO, Amirghahari N, Rong Xiaohua R, Huijuan Z, Harrison L. eIF4E overexpression may confer radioresistance in a head and neck cancer cell line. Otolaryngology-Head and Neck Surgery, 131(2): 178, 2004.
8. Nathan CO, Amirghahari N, Rice C, Abreo F, Shi R, Stucker F. Molecular analysis of surgical margins in HNSCC patients. Laryngoscope, 112: 2129-2140, 2002.
9. Chandy B, Abreo F, Nassar R, Stucker F, Nathan CO. Expression of the proto-oncogene eIF4E in inflammation of the oral cavity. Otolaryngology Head and Neck Surgery, 126: 290-295, 2002.
10. Nathan CO, Sanders K, Abreo F, Nassar R, Glass J. Correlation of p53 and the proto-oncogene eIF4E in Larynx Cancers: Prognostic Implications. Cancer Research, 60: 3599-3604, 2000.
11. DeFatta R, Nathan CO, De Benedetti A. Reducing the level of eIF4E with antisense RNA suppresses the oncogenic properties of Head and Neck Squamous Cell Carcinoma Cell Line. Laryngoscope, 110 (6): 928-933, 2000.
12. Franklin S, Pho T, Abreo F, Nassar R, De Benedetti A, Stucker F, Nathan CO. Immunohistochemical Detection of the Proto-Oncogene eIF4E in Larynx and Hypopharynx Cancers. Archives of Otolaryngology/Head & Neck Surgery, 125:177-182, 1999.
13. Nathan CO, Franklin S, Abreo F, Nassar R, De Benedetti A, Glass J. Analysis of Surgical Margins with the Molecular Marker eIF4E: a prognostic factor in patients with Head & Neck Cancer. J Clin Oncol, 17 (9): 2909-2914, 1999.
14. Nathan CO, Franklin S, Abreo F, Nassar R, De Benedetti A, Williams J, Stucker F. Expression of eIF4E during head & neck tumorigenesis: possible role in angiogenesis. Laryngoscope, 109 (8); 1253-1258; 1999.
15. Sorrells D, Ghali G, De Benedetti A, Nathan CO, Li BD. Progressive Amplification and Overexpression of the Eukaryotic Initiation Factor 4E Gene in Different Zones of Head and Neck Cancers. J Oral Maxillofac Surg, 57(3):294-299, 1999.
16. Sorrells D, Ghali G, Meschonat C, DeFatta R, Black D, Liu L, De Benedetti A, Nathan CO, Li BD. Competitive PCR to Detect eIF4E Gene Amplification in Head and Neck Cancer. Head & Neck, 21: 60-65, 1999.
17. Nathan CO, Liu L, Li B, Abreo F, Nandy I, De Benedetti A. Detection of the proto-oncogene eIF-4E in surgical margins may predict recurrence in head and neck cancer. Oncogene, 15: 579-584, 1997.
18. Nathan CO, Carter P, Liu L, Li B, Abreo F, Tudor A, Zimmer S, De Benedetti A. Elevated expression of eIF-4E and FGF-2 isoforms during vascularization of breast carcinomas. Oncogene, 15: 1087-1095, 1997.
19. Sorrells DL, Meschonat C, De Benedetti A, Nathan CO, Ghali G, Li BD. Gene Amplification and protein elevation of eIF4E in Head and Neck Squamous Cell Carcinoma. J. Oral Maxillofacial Surgery, 55(8) Supp. 3: 65-66, 1997.