Gary Nabel

{{Short description|American virologist and immunologist}}

{{Multiple issues|

{{peacock|date=August 2023}}

{{Like resume|date=August 2023}}

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{{Infobox scientist

|name = Gary J. Nabel

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|birth_name =

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|fields =Virology, Immunology

|workplaces =Sanofi
National Institute of Allergy and Infectious Diseases
Brigham and Women's Hospital
Harvard Medical School
University of Michigan

|alma_mater =Harvard University
Brigham and Women’s Hospital

}}

Gary J. Nabel is an American virologist and immunologist. He serves as the president and chief executive officer of ModeX Therapeutics, located in Natick, Massachusetts. He was the founding director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), a position he held from 1999 until an unspecified date.{{Cite web |last=Malakoff |first=David |date=1999-03-10 |title=Nabel to Head AIDS Vaccine Institute |url=https://www.science.org/content/article/nabel-head-aids-vaccine-institute |url-status=live |archive-url=https://web.archive.org/web/20220212031658/https://www.science.org/content/article/nabel-head-aids-vaccine-institute |archive-date=2022-02-12 |access-date=2025-03-16 |website=www.science.org |language=en}}

Education

Nabel completed his undergraduate studies at Harvard University in 1975, followed by an M.D. in 1980 and Ph.D. in 1982 from the same institution. His dissertation research was conducted in the laboratory of immunologist Harvey Cantor. He then worked as a postdoctoral fellow in the laboratory of David Baltimore at the Whitehead Institute, studying the regulation of HIV gene expression by the transcription factor NF-κB.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.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}}. He completed his Internal Medicine residency at Brigham and Women’s Hospital.

Career

Nabel joined the faculty of the University of Michigan in 1987, where he led a research laboratory focusing on infectious diseases and cancer immunotherapy. He was an investigator at the Howard Hughes Medical Institute until 1999,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. researching transcriptional regulation of cell and viral gene expression, as well as viral vectors in gene therapy.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– He also held the title of Sewell Professor of Internal Medicine and Biological Chemistry.

In 1999, Nabel was recruited to establish a vaccine research program at the NIH in Washington, D.C. He served as the founding director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases within NIH and subsequently as a senior investigator with tenure. At NIH, he oversaw basic, clinical, and translational research on vaccine strategies, advocating for a structure-based approach to vaccine design. This work included basic science and clinical trials, such as over 100 clinical studies conducted in the United States, Europe, and Africa, involving candidates for SARS, Chikungunya, universal influenza, and Ebola vaccines.

Nabel moved to Sanofi in 2012, serving as chief scientific officer and senior vice president. He oversaw the Breakthrough Lab, which developed tri-specific antibodies that are now in development for HIV.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. He also provided oversight of the Sanofi global R&D research portfolio.

Nabel co-founded ModeX Therapeutics in 2020.{{cite news |last1=Incorvaia |first1=Darren |title=ModeX's multispecific antibodies shut down COVID variants and advance to the clinic with $35M more BARDA bucks |url=https://www.fiercebiotech.com/research/modexs-multispecific-antibodies-shut-down-covid-variants-and-advance-clinic-35m-more-barda |access-date=22 April 2025 |date=October 9, 2024}} In May 2022, ModeX Therapeutics was acquired by OPKO Health.{{cite news |last1=Pandey |first1=Pragya |title=Is OPKO Health A Diagnostics Stock Worth Buying? |url=https://www.entrepreneur.com/business-news/is-opko-health-a-diagnostics-stock-worth-buying/429023 |access-date=22 April 2025 |publisher=Entrepreneur |date=June 7, 2022}}

Biomedical research

At the University of Michigan, Nabel's basic research investigated gene transfer,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}}. basic mechanisms of HIV gene regulation, and NF-κB transcriptional control.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. Branswell, Helen (2016-03-17). "Sanofi science chief says it's to time 'think big' about Zika". Retrieved 2017-04-03.

As founding director of the NIH’s Vaccine Research Center, Nabel contributed to vaccine development efforts. Research utilizing molecular genetics and viral replication structure contributed to developing a vaccine candidate against Ebola using gene-based immunization, which demonstrated protection against infection in non-human primates.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.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.

This work provided a conceptual basis for the VSV vaccine. Research also included the development of a Chikungunya virus vaccine effective in primates and contributions to the advancement of universal influenza vaccines. Utilizing a structure-based approach to vaccine design, research elucidated broadly protective human immune responses to HIV,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. leading to the discovery by him and his colleagues from the VRC of broadly neutralizing antibodies to the highly conserved CD4 binding site of HIV. An antibody platform, tri-specific antibodies, was developed, which showed anti-HIV activity in studies and advanced into human trials.

Nabel applied molecular immunology and virology analysis to identify genes critical to Ebola replication and assembly. Research demonstrated that gene-based prime-boost immunization stimulates cellular and humoral immune responses. Research led to developing a protective vaccine candidate for the Ebola virus tested in non-human primates,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. defined its immune mechanism of protection, and guided its development and testing in Africa. Research contributed to advancing novel SARSYang 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.

and pandemic influenzaKong 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.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. vaccine candidates into clinical trials and identifying potential candidates for encephalitis viruses and EBV.

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

At Sanofi, Nabel's work included the development of an antibody platform capable of recognizing three targets in a single protein, tri-specific antibodies, now under evaluation for the treatment and prevention of AIDS and cancer.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.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.

Awards

Nabel's honors include the Amgen Scientific Achievement Award from the American Society for Biochemistry and Molecular Biology,{{Citation |last1=Infections |first1=Institute of Medicine (US) Forum on Emerging |title=Forum Member, Speaker, and Staff Biographies |date=2002 |work=Biological Threats and Terrorism: Assessing The Science and Response Capabilities: Workshop Summary |url=https://www.ncbi.nlm.nih.gov/books/NBK98414/ |access-date=2024-11-24 |publisher=National Academies Press (US) |language=en |last2=Knobler |first2=Stacey L. |last3=Mahmoud |first3=Adel AF |last4=Pray |first4=Leslie A.}} The Health and Human Services Secretary’s Award for Distinguished Service, the [https://geoffreybeenefoundation.com/science-award/#:~:text=The%20Geoffrey%20Beene%20Foundation%20is,the%20forefront%20of%20scientific%20research. Geoffrey Beene Foundation Builders of Science] Award from [https://researchamericainc.com Research America], and the James Tolbert Shipley Prize for Research at Harvard Medical School. 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 AAAS. 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 the Board of Directors for the Keystone Symposia{{Cite web |date=2024 |title=Leadership |url=https://www.opko.com/company/leadership#group_1-5 |access-date=2024-11-24 |website=OPKO Health, Inc. |language=en}} from 2017 to 2019. He was 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

  • {{Cite journal| last = Dolgin | first = Elie| doi = 10.1038/nm0313-256| pmid = 23467227| issn = 1078-8956| volume = 19| issue = 3| pages = 256| title = Straight talk with Gary Nabel| journal = Nature Medicine| date = 2013-03-06| s2cid = 205377266| doi-access = free}}
  • {{Cite news| last = Branswell| first = Helen| title = Sanofi science chief says it's to time 'think big' about Zika| accessdate = 2017-04-03| date = 2016-03-17| url = https://www.statnews.com/2016/03/17/zika-gary-nabel-sanofi/}}
  • {{Cite news| last = Gokhale| first = Ketaki| title = Sanofi Sees Cure for Cancer Woes in Moving West for Acquisitions | work = Bloomberg| accessdate = 2017-04-03|date = 2016-07-12| url = https://www.bloomberg.com/news/articles/2016-07-12/sanofi-sees-cure-for-cancer-woes-in-moving-west-for-acquisitions}}
  • [http://www.aditecproject.eu/about-aditec/external-advisory-board/dr-gary-nabel.html Advisory board bio page] for the EU-funded Advanced Immunization Technologies project

= Notes =

{{Reflist}}

Selected publications

See [https://scholar.google.com/scholar?q=gary%20nabel Google Scholar] for citation information.

  • {{Cite journal| doi = 10.1038/326711a0| issn = 0028-0836| volume = 326| issue = 6114| pages = 711–713| last1 = Nabel| first1 = Gary| last2 = Baltimore| first2 = David| title = An inducible transcription factor activates expression of human immunodeficiency virus in T cells| journal = Nature| date = 1987-04-22| pmid = 3031512| bibcode = 1987Natur.326..711N| s2cid = 4317942}}
  • {{Cite journal| issn = 0027-8424| volume = 86| issue = 7| pages = 2336–2340| last1 = Osborn| first1 = L.| last2 = Kunkel| first2 = S.| last3 = Nabel| first3 = G. J.| title = Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B| journal = Proceedings of the National Academy of Sciences| date = 1989-04-01| pmid = 2494664| pmc = 286907| doi = 10.1073/pnas.86.7.2336| doi-access = free| bibcode = 1989PNAS...86.2336O}}
  • {{Cite journal| issn = 0027-8424| volume = 90| issue = 23| pages = 11307–11311| last1 = Nabel| first1 = G. J.| last2 = Nabel| first2 = E. G.| last3 = Yang| first3 = Z. Y.| last4 = Fox| first4 = B. A.| last5 = Plautz| first5 = G. E.| last6 = Gao| first6 = X.| last7 = Huang| first7 = L.| last8 = Shu| first8 = S.| last9 = Gordon| first9 = D.| last10 = Chang| first10 = A. E.| title = Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans| journal = Proceedings of the National Academy of Sciences| date = 1993-12-01| pmid = 8248244| pmc = 47971| doi = 10.1073/pnas.90.23.11307| doi-access = free| bibcode = 1993PNAS...9011307N}}
  • {{Cite journal| doi = 10.1126/science.1187659| issn = 0036-8075| volume = 329| issue = 5993| pages = 856–861| last1 = Wu| first1 = Xueling| last2 = Yang| first2 = Zhi-Yong| last3 = Li| first3 = Yuxing| last4 = Hogerkorp| first4 = Carl-Magnus| last5 = Schief| first5 = William R.| last6 = Seaman| first6 = Michael S.| last7 = Zhou| first7 = Tongqing| last8 = Schmidt| first8 = Stephen D.| last9 = Wu| first9 = Lan| last10 = Xu| first10 = Ling| last11 = Longo| first11 = Nancy S.| last12 = McKee| first12 = Krisha| last13 = O’Dell| first13 = Sijy| last14 = Louder| first14 = Mark K.| last15 = Wycuff| first15 = Diane L.| last16 = Feng| first16 = Yu| last17 = Nason| first17 = Martha| last18 = Doria-Rose| first18 = Nicole| last19 = Connors| first19 = Mark| last20 = Kwong| first20 = Peter D.| last21 = Roederer| first21 = Mario| last22 = Wyatt| first22 = Richard T.| last23 = Nabel| first23 = Gary J.| last24 = Mascola| first24 = John R.| title = Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1| journal = Science| date = 2010-08-13| pmid = 20616233| pmc = 2965066| bibcode = 2010Sci...329..856W}}

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Category:Howard Hughes Medical Investigators

Category:Living people

Category:Members of the National Academy of Medicine

Category:Sanofi people

Category:Year of birth missing (living people)

Category:American virologists

Category:Harvard College alumni

Category:University of Michigan faculty

Category:Harvard Medical School alumni

Category:Fellows of the American Academy of Microbiology

Category:Harvard Graduate School of Arts and Sciences alumni