Gary Nabel

American virologist and immunologist

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Gary J. Nabel

Alma mater| Harvard University
Brigham and Women’s Hospital
Scientific career
Fields| Virology, Immunology
Institutions| Sanofi
National Institute of Allergy and Infectious Diseases
Brigham and Women's Hospital
Harvard Medical School
University of Michigan

Gary J. Nabel is an American virologist and immunologist who is President and chief executive officer of ModeX Therapeutics in Natick, Massachusetts. He was the founding director of Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.

## Education

[edit]

Nabel completed his undergraduate, M.D., and Ph.D. studies at Harvard University (1975, 1980, and 1982, respectively). He completed his dissertation research in the laboratory of immunologist Harvey Cantor and then worked as a postdoctoral fellow in the laboratory of David Baltimore at the Whitehead Institute, studying regulation of HIV gene expression by the recently discovered NF-κB, a host transcription factor.[1][2] He completed his Internal Medicine residency at Brigham and Women’s Hospital.

## Career

[edit]

Nabel joined the faculty of the University of Michigan in 1987, where he led a research lab focused on infectious diseases and cancer immunotherapy. Nabel was an investigator of the Howard Hughes Medical Institute until 1999,[3] working on transcriptional regulation of cell and viral gene expressions, as well as viral vectors in gene therapy.[4] He was the Sewell Professor of Internal Medicine and Biological Chemistry.

In 1999, Nabel was recruited to build a vaccine research program for the country at the National Institutes of Health in Washington, DC. He served as the founding director of Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, NIH and senior investigator with tenure at the National Institute of Allergy and Infectious Diseases. At NIH, Nabel pioneered a renaissance in vaccine development through structure-based rational vaccine design. Nabel provided overall direction and scientific leadership of the basic, clinical, and translational research activities and guided development of novel vaccine strategies. This vaccine work spanned basic science to clinical trials, including more than 100 clinical studies in the United States, Europe, and Africa, including SARS, Chikungunya, universal influenza vaccines and Ebola vaccines eventually tested in Africa.

Nabel moved to Sanofi in 2012, and as chief scientific officer and senior vice president, he oversaw the Breakthrough Lab, which developed the first trispecific antibodies now in development for HIV.[5] He also provided oversight of the Sanofi global R&D research portfolio, helping to guide more than ten products a year into clinical efficacy trials and bringing numerous products to licensure.

Nabel is currently president and chief executive officer for ModeX Therapeutics in Natick, Massachusetts.

## Biomedical research

[edit]

At the University of Michigan, Nabel’s basic research investigated gene transfer,[6] basic mechanisms of HIV gene regulation and NF-κB transcriptional control.[7][8]

As founding director of NIH’s Vaccine Research Center, Nabel pioneered a renaissance in vaccine development through his rational approach to vaccine design. Understanding the molecular genetics and structure of viral replication, he discovered the first vaccine against Ebola, using gene-based immunization to completely protect against infection in non-human primates.[9][10] This work provided the conceptual basis that served as a prototype for the VSV vaccine recently proven efficacious in humans. He developed the first Chikungunya virus vaccine effective in primates and advanced universal influenza vaccines of unprecedented breadth and potency. His rational approach to structure-based vaccine design led to elucidation of broadly protective human immune responses to HIV,[11] leading to the discovery of broadly neutralizing antibodies to the highly conserved CD4 binding site of HIV with his colleagues from the VRC. Recently, he created an innovative antibody platform, trispecific Abs, that show unprecedented anti-HIV breadth and potency. These antibodies have advanced into human trials.

Recognizing the threat of Ebola virus decades ago, he applied molecular immunology and virology analysis to identify genes critical to Ebola replication and assembly. Importantly, he showed that gene-based prime-boost immunization stimulates potent cellular and humoral immune responses and discovered the first protective vaccine for highly lethal Ebola virus in non-human primates,[12] defined its immune mechanism of protection, and guided its development and testing in Africa. His work has stimulated international progress against emerging pathogens, having advanced novel SARS[13] and pandemic influenza.[14][15] vaccines into clinical trials in record time, while creating promising candidates for encephalitis viruses and EBV.

At NIH’s Vaccine Research Center, he also contributed seminal advances to vaccine science neutralizing antibodies against HIV, universal influenza,[16] Ebola,[17] Chikungunya,[18] and Epstein-Barr virus.[19] He led research on viral molecular biology, protein structure, and immunotherapy, which defined modes of immune escape and led to the discovery of the broadly neutralizing antibodies to the highly conserved CD4 binding site of HIV that are now in human efficacy trials in Africa.[20]

At Sanofi, Nabel developed a novel antibody platform that can recognize three targets in a single protein, trispecific antibodies, now under evaluation for the treatment and prevention of AIDS and cancer.[21][22]

## Awards

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Nabel’s honors include the Amgen Scientific Achievement Award from the American Society for Biochemistry and Molecular Biology, the Health and Human Services Secretary’s Award for Distinguished Service, and the Geoffrey Beene Foundation Builders of Science Award from Research!America. He received an honorary degree from the University of London, as well as the U.S. Army Medical Department’s Order of Military Medical Merit. Nabel is an elected fellow of the Association of American Physicians, the American Academy of the Arts and Sciences, and the American Association for the Advancement of Science. Nabel was elected to the American Society for Clinical Investigation in 1992 and the National Academy of Medicine in 1998.

Nabel served as the Chair of Board of Directors for the Keystone Symposia from 2017 to 2019. He as a Council Delegate to the AAAS, Medical Sciences Section from 1997 to 2002, and served as the editor for the Journal of Virology from 1995 to 2005.

## References

[edit]

* Dolgin, Elie (2013-03-06). "Straight talk with Gary Nabel". Nature Medicine. 19 (3): 256. doi:10.1038/nm0313-256. ISSN 1078-8956. PMID 23467227. S2CID 205377266.
* Branswell, Helen (2016-03-17). "Sanofi science chief says it's to time 'think big' about Zika". Retrieved 2017-04-03.
* Gokhale, Ketaki (2016-07-12). "Sanofi Sees Cure for Cancer Woes in Moving West for Acquisitions". Bloomberg. Retrieved 2017-04-03.
* Advisory board bio page for the EU-funded Advanced Immunization Technologies project

### Notes

[edit]

1. ^ Nabel, Gary; Baltimore, David (1987-04-22). "An inducible transcription factor activates expression of human immunodeficiency virus in T cells". Nature. 326 (6114): 711–713. doi:10.1038/326711a0. ISSN 0028-0836. PMID 3031512. S2CID 4317942.
2. ^ Osborn, L.; Kunkel, S.; Nabel, G. J. (1989-04-01). "Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B". Proceedings of the National Academy of Sciences. 86 (7): 2336–2340. doi:10.1073/pnas.86.7.2336. ISSN 0027-8424. PMC 286907. PMID 2494664.
3. ^ Dolgin, Elie (2013-03-06). "Straight talk with Gary Nabel". Nature Medicine. 19 (3): 256. doi:10.1038/nm0313-256. ISSN 1078-8956. PMID 23467227. S2CID 205377266.
4. ^ Nabel, G. J.; Nabel, E. G.; Yang, Z. Y.; Fox, B. A.; Plautz, G. E.; Gao, X.; Huang, L.; Shu, S.; Gordon, D.; Chang, A. E. (1993-12-01). "Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans". Proceedings of the National Academy of Sciences. 90 (23): 11307–
5. ^ Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 Aug 13;329(5993):856-61. doi: 10.1126/science.1187659. Epub 2010 Jul 8. PMID 20616233; PMCID: PMC2965066.
6. ^ Nabel, G. J.; Nabel, E. G.; Yang, Z. Y.; Fox, B. A.; Plautz, G. E.; Gao, X.; Huang, L.; Shu, S.; Gordon, D.; Chang, A. E. (1993-12-01). "Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans". Proceedings of the National Academy of Sciences. 90 (23): 11307–11311. doi:10.1073/pnas.90.23.11307. ISSN 0027-8424. PMC 47971. PMID 8248244.
7. ^ 5\. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 Aug 13;329(5993):856-61. doi: 10.1126/science.1187659. Epub 2010 Jul 8. PMID 20616233; PMCID: PMC2965066.
8. ^ 6\. Branswell, Helen (2016-03-17). "Sanofi science chief says it's to time 'think big' about Zika". Retrieved 2017-04-03.
9. ^ Xu L, Sanchez A, Yang Z, Zaki SR, Nabel EG, Nichol ST, Nabel GJ. Immunization for Ebola virus infection. Nature Med. 4(1):37-42.
10. ^ Sullivan N, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventative vaccine for Ebola virus infection in primates. Nature 408(6812):605-609.
11. ^ Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang S-H, Yang X, Zhang M- Y, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ, Kwong PD. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445(7129):732-7.
12. ^ Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8(+) cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat. Med. 17(9):1128-1131.
13. ^ Yang Z-Y, Kong W-P, Huang Y, Roberts A, Murphy B, Subbarao K, Nabel GJ. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428(6982):561-564.
14. ^ Kong W-P, Hood C, Yang Z-Y, Wei C-J, Xu L, Garcia-Sastre A, Tumpey TM, Nabel GJ. Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination. Proc. Natl. Acad. Sci. U.S.A. 103(43):15987- 15991.
15. ^ Wei C-J, Boyington JC, McTamney PM, Kong W-P, Pearce MB, Anderson H, Rao S, Tumpey TM, Yang Z-Y, Nabel GJ. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science 329(5995):1060-1064.
16. ^ Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, Rao SS, Kong WP, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 499(7456):102-6.
17. ^ Sullivan NJ, Geisbert TW, Geisbert JB, Xu L, Yang Z-Y, Roederer M, Koup RA, Jahrling PB, Nabel GJ. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 424(6949):681-684.
18. ^ Akahata W, Yang Z-Y, Andersen H, Sun S, Holdaway HA, Kong W-P, Lewis MG, Higgs S, Rossman MG, Rao S, Nabel GJ. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat. Med. 16(3):334-338.
19. ^ Kanekiyo M, Bu W, Joyce MG, Meng G, Whittle JR, Baxa U, Yamamoto T, Narpala S, Todd JP, Rao SS, McDermott AB, Koup RA, Rossmann MG, Mascola JR, Graham BS, Cohen JI, Nabel GJ, Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell.162(5):1090-1100.
20. ^ 7\. Pegu A, Yang ZY, Boyington JC, Wu L, Ko SY, Schmidt SD, McKee K, Kong WP, Shi W, Chen X, Todd JP, Letvin NL, Huang J, Nason MC, Hoxie JA, Kwong PD, Connors M, Rao SS, Mascola JR, Nabel GJ. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci. Transl. Med. 6(243):243ra88, 2014.
21. ^ 8\. Wu L, Seung E, Xu L, Rao E, Lord DM, Wei RR, Cortez-Retamozo V, Ospina B, Posternak V, Ulinski G, Piepenhagen P, Francesconi E, El-Murr N, Beil C, Kirby P, Li A, Fretland J, Vicente R, Deng GJ, Dabdoubi T, Cameron B, Bertrand T, Ferrari P, Pouzieux S, Lemoine C, Prades C, Park A, Qiu HW, Song ZL, Zhang BL, Sun FX, Chiron M, Rao S, Radošević R, Yang Z-Y & Nabel GJ. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nat Cancer 2019. doi:10.1038/s43018-019-0004-z.
22. ^ 9\. Xu L, Pegu A, Rao E, Doria-Rose N, Beninga J, McKee K, Lord DM, Wei RR, Deng G, Louder M, Schmidt SD, Mankoff Z, Wu L, Asokan M, Beil C, Lange C, Leuschner WD, Kruip J, Sendak R, Kwon YD, Zhou T, Chen X, Bailer RT, Wang K, Choe M, Tartaglia LJ, Barouch DH, O'Dell S, Todd JP, Burton DR, Roederer M, Connors M, Koup RA, Kwong PD, Yang ZY, Mascola JR, Nabel GJ. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science. 2017 Oct 6;358(6359):85-90. doi: 10.1126/science.aan8630. Epub 2017 Sep 20. PMID 28931639; PMCID: PMC5978417.

## Selected publications

[edit]

See Google Scholar for citation information.

* Nabel, Gary; Baltimore, David (1987-04-22). "An inducible transcription factor activates expression of human immunodeficiency virus in T cells". Nature. 326 (6114): 711–713. Bibcode:1987Natur.326..711N. doi:10.1038/326711a0. ISSN 0028-0836. PMID 3031512. S2CID 4317942.
* Osborn, L.; Kunkel, S.; Nabel, G. J. (1989-04-01). "Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B". Proceedings of the National Academy of Sciences. 86 (7): 2336–2340. Bibcode:1989PNAS...86.2336O. doi:10.1073/pnas.86.7.2336. ISSN 0027-8424. PMC 286907. PMID 2494664.
* Nabel, G. J.; Nabel, E. G.; Yang, Z. Y.; Fox, B. A.; Plautz, G. E.; Gao, X.; Huang, L.; Shu, S.; Gordon, D.; Chang, A. E. (1993-12-01). "Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans". Proceedings of the National Academy of Sciences. 90 (23): 11307–11311. Bibcode:1993PNAS...9011307N. doi:10.1073/pnas.90.23.11307. ISSN 0027-8424. PMC 47971. PMID 8248244.
* Wu, Xueling; Yang, Zhi-Yong; Li, Yuxing; Hogerkorp, Carl-Magnus; Schief, William R.; Seaman, Michael S.; Zhou, Tongqing; Schmidt, Stephen D.; Wu, Lan; Xu, Ling; Longo, Nancy S.; McKee, Krisha; O’Dell, Sijy; Louder, Mark K.; Wycuff, Diane L.; Feng, Yu; Nason, Martha; Doria-Rose, Nicole; Connors, Mark; Kwong, Peter D.; Roederer, Mario; Wyatt, Richard T.; Nabel, Gary J.; Mascola, John R. (2010-08-13). "Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1". Science. 329 (5993): 856–861. Bibcode:2010Sci...329..856W. doi:10.1126/science.1187659. ISSN 0036-8075. PMC 2965066. PMID 20616233.

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