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BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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NAME
POSITION TITLE
PAGANO, Joseph
Lineberger Professor of Cancer Research,
Professor of Medicine and Microbiol. & Immunol.
Director Emeritus, Lineberger Cancer Center
eRA COMMONS USER NAME (credential, e.g., agency login)
Joseph_Pagano
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
University of Rochester, Rochester, NY
Yale University, New Haven, CT
Massachusetts Memorial Hosp., Boston, MA
Peter Bent Brigham Hosp., Boston, mA
Karolinska Inst., Stockholm, Sweden
DEGREE
(if applicable)
A.B.
M.D.
Intern
Resident
Res Assoc
YEAR(s)
1953
1957
1957-58
1960-61
1961-62
FIELD OF STUDY
English, Honors
Medicine
Medicine
Medicine
Virology
A. Positions and Honors
Positions and Employment
1958-60; 62-65: Postdoctoral Fellow & Asst. Member, Wistar Inst., Philadelphia, PA
1965-73:
Asst. & Assoc. Prof. of Medicine & Microbiology, Univ. of North Carolina at Chapel Hill
1970-71:
Visiting Professor, Swiss Inst. for Cancer Rsch., Lausanne, Switzerland
1973-Present: Professor of Medicine & Microbiol., Univ. North Carolina at Chapel Hill
1974-97:
Director, Lineberger Comprehensive Cancer Center, Univ. of North Carolina at Chapel Hill
1997-Present Director Emeritus, Lineberger Comp. Cancer Center, Univ. of North Carolina at Chapel Hill
1986-Present: Lineberger Professor of Cancer Research
Other Experience and Professional Memberships (selected)
1973-79
NIH Virology Study Section. And ad hoc member, 2002-present
1990-94
President, Internat'l. Assoc. for Res. in EBV and Associated Diseases
1997-99
President and Chairman of the Board, Association of American Cancer Institutes
2001
Chair, Viruses and Human Cancer Workshop, NCI
2001-06
Co-Organizer, annual NCI International AIDS Malignancy Conference
2002
Consultant, NCI Initial Review Groups
2002
Organizer, “Cancer Cells”, Annual Symposium, Cold Spring Harbor
2003
Chair, Board of Directors, Global Vaccines, Inc. (not for profit company)
2004
Chair, Institute of Medicine Committee on Alternative Funding Strategies for DOD’s
Congressionally Directed Medical Research Programs
2008
Member, Advisory Committee, Burroughs Welcome Fund Institutional Program Unifying
Population and Laboratory Based Sciences
Honors
1968-73 U.S.P.H.S. Research Career Development Award
1990
First Gertrude and Werner Henle Lectureship In Viral Oncology
1993-01 Member, Board of Directors, Burroughs Wellcome Fund
1996
The North Carolina Award in Science
1996
McLaughlin Visiting Professor, The University of Texas Medical Branch
1997
Norma Berryhill Distinguished Lecturer, University of North Carolina
1997
Harry Eagle Lecturer, Albert Einstein College of Medicine
1997-01 Member, Awards Assembly of the General Motors Cancer Research Foundation
1998Institute of Medicine, Member
2002
Joseph and Ruth McCartney Hauck Lecturer, Mayo Clinic
2003
Lecturer, Japan Society for Head & Neck Cancer; 100th Anniversary, ENT Dept., Kanazawa Univ.
2004
Fellow, American Association for the Advancement of Science
B. Selected publications (from 331 total): (in chronological order)
1. Zhang, L. and Pagano, J.S. Interferon regulatory factor 7 mediates activation of Tap-2 by Epstein-Barr
Virus Latent Membrane Protein 1, J Virol, 75: 341-350, 2001.
2. Murono, S, Inoue, H., Tanabe, T. and Pagano, J.S., Induction of cyclooxygenase-2 by Epstein-Barr virus
latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal
carcinoma cells, Proc Nat Acad of Sci, USA 98: 6905-6910, 2001.
3. Murono, S, Raab-Traub, N. and Pagano, J.S. Prevention and inhibition of nasopharyngeal carcinoma
growth by antiviral phosphonated nucleoside analogs, Cancer Res. 61:7875-7877, 2001.
4. Zhang, L. and J.S. Pagano. Interferon regulatory factor 7: a key cellular mediator of LMP-1 in EBV latency
and transformation. Seminars in Cancer Biology. pp. 1-9, 2001.
5. Zhang, L., Wu, L. Hong, K. and Pagano, J.S. Intracellular signaling molecules activated by Epstein-Barr
virus for induction of interferon regulatory factor 7. J Virol, 75: 12393-12401, 2001.
6. Zhang, L. and Pagano, J.S., Structure and function of interferon regulatory factor 7, Interferon and
Cytokine Res, 22:95-101, 2002.
7. Gershburg, E. and Pagano, J.S., Phosphorylation of the Epstein-Barr virus DNA polymerase processivity
factor by the EBV-encoded protein kinase and effects of the L-Riboside Benzimidazole 1263W94, J Virol,
76:998-1003, 2002.
8. Pagano, J.S. Viruses and Lymphoma. Perspective. New Engl J Med, 347:78-79, July 11, 2002.
9. Wakisaka, N, Murono S, Yoshizaki T, Furukawa M and Pagano, J.S. Epstein-Barr virus latent membrane
protein 1 induces and causes release of fibroblast growth factor-2, Cancer Res, 62: 6337-6344, 2002.
10. Wong, M, Pagano, J.S. J. Schiller, S. Tevethia, N. Raab-Traub and J. Gruber. Commentary: new
associations of human papillomavirus, Simian Virus 40, and Epstein-Barr Virus with human cancer. J Nat
Cancer Inst, 94: 24, 1832-1836, 2002.
11. Zhang, L. and Pagano, J.S. Interferon Regulatory Factor 7 and virus-cell interactions. Recent Res
Develop Mol & Cell Biol 3:235-241. 2002.
12. Wakisaka, N. and Pagano, J.S. Epstein-Barr Virus induces invasion and metastasis factors. Anticancer
Res., 23:2133-2138, 2003.
13. Ning, S., A. Hahn, L. Huye, Pagano, J.S. Interferon Regulatory Factor 7 regulates expression of
Epstein-Barr Virus Latent Membrane Protein 1: A regulatory circuit. J Virol, 77:9359-9368, 2003.
14. Shackelford, J., C. Maier, Pagano, J.S. Epstein-Barr virus activates -catenin in type III latently infected
B-lymphocyte lines: involvement of deubiquitination, Proc Nat Acad Sci U.S.A., 26:15572-15576, 2003.
15. Wakisaka, N., T. Yoshizaki, S. Murono, M. Furukawa, Pagano, J.S. Epstein-Barr virus latent membrane
protein-1 induces synthesis of hypoxia-inducible factor-l. Mol Cell Biol, 24:5223-5234, 2004.
16. Zhang, L., Hong, K., Zhang, J., and Pagano, J.S. Multiple signal transducers and activators of
transcription are induced by EBV LMP-1. Virology 323, 141-152, 2004.
17. Qing, J., C. Liu, L. Choy, RY Wu, Pagano, J.S. R. Derynck. TGF-/Smad3 signaling regulates IRF-7
function and transcriptional activation of the interferon- promoter. Mol Cell Biol, 24:3-1411-1425, 2004.
18. Yue, W., M. Davenport, J. Shackelford, Pagano, J.S. Mitosis-specific hyperphosphorylation of the
Epstein-Barr Virus Nuclear Antigen-2 suppresses its function. J Virol, 78:3542-3552, 2004.
19. Wang, L., N. Wakisaka, C. Tomlinson, S. DeWire, S. Krall, Pagano, J.S. B, Damania. The Kaposi’s
Sarcoma-Associated Herpesvirus (KSHV/HHV8) K1 protein induces expression of angiogenic and
invasion factors. Cancer Res, 64: 2772-2781, 2004.
20. Gershburg, E., K. Hong, Pagano, J.S. Effect of Maribavir and indolocarbozoles on the Epstein-Barr Virus
protein kinase encoded by the BGLF-4 gene. Antimicrob Agents Chemother, 48: 1900-1903, 2004.
21. Shackleford, J. and Pagano, J.S. Tumor Viruses and Cell-Signaling Pathways: Deubiquitination versus
Ubiquitination. Mol Cell Biol 24:5089-5093, 2004
22. Pagano, J.S., Blaser, M., Buendia, M-A, Damania, B., Khalili, K., Raab-Traub, N, Roizman, B. Infectious
agents and cancer: criteria for a causal relation”. Sem Cancer Biol, 14:453-471, 2004.
23. Pagano, J.S., Preface. Strategies to Leverage Research Funding: Guiding DOD’s Peer Reviewed Medical
Research Programs, ed. by M. McGeary and K. Hanna, Institute of Medicine, the National Academies
Press, Washington D.C., 2004.
24. Gershburg, E., Marschall, J., Hong, K. and Pagano, J.S. Expression and localization of the Epstein-Barr
virus-encoded protein kinase. J Virol 78:22:12140-12146, 2004.
25. Zhang, L., Zhang, J., Lambert, Q., Der, C. Del Valle, L., Miklossy, J., Khalili, K., Zhou, J. and Pagano, J.S.
Interferon regulatory factor 7 is associated with EBV-transformed CNS lymphoma and has oncogenic
properties. J Virol, 78:23:12987-12995, 2004.
26. Wakisaka, N., T. Yoshizaki, S. Murono, M. Furukawa, N. Raab-Traub, Pagano, J.S. Ribonucleotide
reductase inhibitors enhance Cidofovir-induced apoptosis in EBV-positive nasopharyngeal carcinoma
xenografts. Internat J Cancer, 116, 2005.
27. Ning, S, Huye, L. Pagano, J.S. Regulation of the transcriptional activity of the IRF7 promoter by a pathway
independent of interferon signaling. J Biol Chem, 280:12262-70. 2005.
28. Yue, W. Gershburg, E. Pagano, J.S. Epstein-Barr Virus protein kinase phosphorylates EBNA2 and
suppresses EBNA2 transactivation of the LMP1 promoter. J. Virol, 79:5880-5885, 2005.
29. Pagano, J.S. Infectious mononucleosis, http://pier.acponline.org/physicians/diseases/d924/d924.html
[Date accessed: 2005 February 3].PIER, Philadelphia, American College of Physicians, 2005.
30. Ning, S., Huye, L., Pagano, J.S. Regulation of the transcriptional activity of the IRF7 promoter by a
pathway independent of interferon signaling: J. Biol Chem, 13:12262-12270, 2005.
31. Kondo S, Wakisaka N, Schell MJ, Horikawa T, Sheen TS, Sato H, Furukawa M, Pagano, J.S., Yoshizaki T.
Epstein-Barr virus latent membrane protein 1 induces the matrix metalloproteinase-1 promoter via an Ets
binding site formed by a single nucleotide polymorphism: Enhanced susceptibility to nasopharyngeal
carcinoma. Int J Cancer, 115:368-376. 2005.
32. Yoshizaki T., Murono S., Wakisaki N., Pagano, J.S., Furukawa, M. Regulation of angiogenic factors by
Epstein-Barr virus gene products in nasopharyngeal carcinoma. Recent Res Devel Cancer. 6, 1-6, 2005.
33. Gershburg, E., Pagano, J.S. Infectious Mononucleosis and Antiviral Drugs. J. Antimicrob Chemo, 56,
2:277-281, 2005.
34. Yoshizaki, T., Wakisaka, N. and Pagano, J.S. Chapter 12: Epstein-Barr Virus Invasion and Metastasis.
Chapter 12, in Epstein-Barr Virus, ed. by E. Robertson. Caister Academic, Norfolk, England, pp 171-196,
2005.
35. Hahn, A., Huye, L. Ning, S. Webster-Cyriaque, J. Pagano, J.S. Interferon Regulatory Factor-7 is
negatively regulated by the Epstein-Barr virus immediate-early gene, BZLF-1. . J. Virol,
79(15):10040-10052, 2005.
36. Jang, K-L, Shackelford, J, Seo S-Y and Pagano, J.S. Up-regulation of -catenin by a viral oncogene
correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells. Proc Nat Acad of Sci,
102:51:18431-18436, 2005.
37. Shackelford, J and Pagano, J.S. Targeting of host-cell ubiquitin pathways by viruses, ed. by J. Mayer and
R. Layfield, Portland Press, in Essays in Biochemistry,41:139-156, 2005.
38. Ning, S., Huye, L., Pagano, J.S. Interferon Regulatory Factor 5 represses expression of the EBV
oncoprotein LMP1: Braking of IRF7/LMP1 regulatory circuit. J. Virol, 79:11671-11676, 2006.
39. Yue, W., Shackelford, J., Pagano, J.S. Cdc2/Cyclin B1-dependent phosphorylation of EBNA2 at Ser243
regulates its function in mitosis.J. Virol. (80):2045-2050, 2006.
40. Kondo S, Seo SY, Yoshizaki T, Wakisaka N, Furukawa M, Joab I, Jang KL and Pagano, J.S. Epstein-Barr
Virus Latent Membrane Protein 1 upregulates HIF1 through Siah1-mediated down-regulation of Prolyl
Hydroxylases 1 and 3 in nasopharyngeal epithelial cells. Cancer Res. 66: (20) 9870-9877, 2006.
41. Kondo, S., Yoshizaki, T., Wakisaka, N., Murono, S., Jang, KL, Joab, I., Furukawa, M. and Pagano, J.S.
MUC1 induced by Epstein-Barr Virus Latent Membrane Protein 1 causes dissociation of cell-matrix
interaction and cellular invasiveness via NF-B and STAT signaling. J. Virol, 81: (4) 1554-1562, 2007.
42. Huye, L., Ning S., Pagano, J.S. Interferon Regulatory Factor 7 is activated by a viral oncoprotein: through
RIP-dependent ubiquitination. Mol Cell Biol. 27:8:2910-2918, 2007.
43. Horikawa T, Yang J, Kondo S, Yoshizaki T, Joab I, Furukawa M and Pagano, J.S. Twist and
Epithelial-Mesenchymal Transition are induced by the EBV oncoprotein Latent Membrane Protein 1 and
are associated with metastatic nasopharyngeal carcinoma. Cancer Res 67: (5)1970-1978, 2007.
44. Pagano, J.S. Is Epstein-Barr Virus Transmitted Sexually? Editorial, JID 195: 469-470, 2007.
45. Gershburg, E, Raffa, S, Torrisi, MR, Pagano, JS. Epstein-Barr Virus-Encoded Protein Kinase (BGLF4) is
involved in production of infectious virus. J. Virol. 80(10): 5407-5412, 2007.
46. Shackelford J. and Pagano, J.S. Role of the ubiquitin system and tumor viruses in AIDS-related cancer. In
Current Biodata Ltd., London, UK, 2007.
47. Ceccarelli, S. Wakisaka, N. Pagano, J.S. Torrisi, M.R. Epstein-Barr virus latent membrane protein 1
promotes concentration in multivesicular bodies of fibroblast growth factor 2 and its release through
exosomes. International Journal of Cancer. 2007. 121(7): 1494-1506.
48. Jung, J.K. Arora, P. Pagano, J.S. Jang, K.L. Expression of DNA methyltransferase 1 is activated by
hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1
pathway. Cancer Res. 2007. 67(12):5771-8.
49. Gershburg, E. and Pagano, J.S. Conserved herpesvirus protein kinases: past, present and future.
Biochim, Biophys. Acta. Proteins and proteomics. 1784(1): 203-202, 2007.
50. Ning, S., Campos, A.D., Darnay, B.G., Bentz, G., and Pagano, J.S. TRAF6 and the three C-terminal
lysine sites on IRF7 are required for its ubiquitination-mediated activation by the TNFR family member
LMP1. Mol. Cell. Biol., 2008. 28(10): (In press)
Manuscripts in Preparation:
1. Whitehurst, C. B. Shackelford, J. Dufour, F. Gershburg, E. Bentz, G. Langelier, Y. Pagano, J. S. The EBV
deubiquitinating enzyme, BPLF1, targets the EBV ribonucleotides reductase.
2. Endo, K. Kondo, S. Shackelford, J. Horikawa, T. Kitagawa, N. Yoshizaki, T. Furukawa, M. Pagano, J. S.
Epstein Barr virus latent membrane protein 1 enhances cell migration by modulating phosphorylation of
Ezrin.
3. Seaman, W. T., Holley-Guthrie, E., Gershburg, E., Delecluse, H.-J., Pagano, J. S. and S. C. Kenney.
BMRF1 transcriptional function, but not BMRF1 phosphorylation by the BGLF4-encoded viral kinase, is
important for Epstein-Barr virus replication.
4. Seaman, W. T., Gershburg, E., Delecluse, H.-J., Pagano, J. S. and S. C. Kenney. Effects of the
EBV-encoded viral kinase, EBV-PK, on BZLF1 function and SUMO-modification.
C. Research Support
Ongoing Research Support
 1-RO1-HL64851 (Pagano)
8/1/05–7/31/10
NIH IRB Exempt
New EBV Therapies for Treatment of Malignancies
The goal of this grant application is to eliminate B-cell selectively derived lymphoma and leukemia cells in cancer
patients using a novel combinatorial gene therapy strategy for Burkitt B lymphoma based vector targeting.
Role: Principal Investigator
 2-P01-CA19014 (Raab-Traub)
4/15/05–3/31/10
NCI
Herpesviral Oncogenesis, Latency & Reactivation - Proj. 4: Cellular Regulation of Type III EBV Latency
Expression of EBNA-2 is linked to cell cycle in Type III latency and suppressed in mitosis. The
B-catenin/TCF signaling pathway is activated in Type III latency.
Role: Subproject PI
 5-T32-CA09156 (Pagano)
7/01/05 – 6/30/10
NCI
IRB: 00-MED-412-ORC
Basic Mechanisms of Viral and Chemical Carcinogenesis
Purpose of this proposal is to provide continuing support for an organized program of interdisciplinary training for
24 postdoctoral fellows in defined areas of basic research that are likely to lead to insights into fundamental
mechanisms of cancer.
Role: Principal Investigator
Pending
1R01AI081904-01 (Pagano)
04/01/09–03/31/14
NIH
IRF7 ubiquitination, activation, and regulation of MyD88-dependent antiviral signaling
To elucidate the mechanism through which ubiquitination activates IRF7 in response to viral infection
and EBV LMP1, understand multiple roles of IRF7 in antiviral responses, and elaborate on regulation of
IRF7 in the EBV context.
Role: Principal Investigator