Michel C. Nussenzweig

Last updated
Michel C. Nussenzweig
Nussenzweig 2015.1446150841.jpg
Born (1955-02-10) February 10, 1955 (age 68)
São Paulo, Brazil
Education
Alma mater New York University (B.A., 1975)
Spouse Svetlana Mojsov
Scientific career
Fields Immunology
Molecular Biology
Institutions The Rockefeller University

Michel C. Nussenzweig (born February 10, 1955) is a professor and head of the Laboratory of Molecular Immunology at The Rockefeller University and a Howard Hughes Medical Institute investigator. He is a member of both the US National Academy of Medicine and the US National Academy of Sciences.

Contents

Education and career

Nussenzweig graduated summa cum laude with a B.A. degree from New York University College of Arts and Sciences in 1975. He earned a Ph.D. from The Rockefeller University in 1981 in cellular immunology, working in Zanvil A. Cohn’s laboratory with Ralph M. Steinman on groundbreaking studies of mouse dendritic cells.

As a Ph.D. student, Nussenzweig was the first to show that dendritic cells present foreign antigens to initiate T cell immunity. [1] He also produced the first dendritic cell-specific monoclonal antibody and cloned the first dendritic cell receptor. [2]

Nussenzweig received an M.D. from New York University School of Medicine in 1982 and completed his internship and residency in internal medicine, and a clinical fellowship in infectious diseases at Massachusetts General Hospital in 1985. From 1986 to 1989, he was a postdoctoral fellow in genetics in the Harvard Medical School laboratory of Philip Leder. Nussenzweig returned to The Rockefeller University as an assistant professor in 1990 and he became an associate professor in 1994, and a professor and senior physician in 1996. In 2013, he was named the first Zanvil A. Cohn and Ralph M. Steinman Professor. [3] [4]

Summary of research achievements

Nussenzweig studies molecular aspects of the immune system’s adaptive and innate responses, using a combination of biochemistry, molecular biology, and genetics. Work on adaptive immunity focuses on B lymphocytes and antibodies to HIV-1, while work on innate immunity focuses on dendritic cells. [5] The laboratory has isolated and cloned human antibodies to HIV-1 and explored their roles in prevention and therapy. In clinical trials, a broadly neutralizing antibody isolated from an HIV-infected patient was shown to be safe and effective and to interfere with chronic infection in a way that traditional antiretroviral therapy does not. [6] [7] His research has led to the development of innovative vaccines against infectious diseases and new treatments for autoimmunity. [8] [9]

Awards and honors

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References

  1. Nussenzweig, M. C.; Steinman, R. M. (1 May 1980). "Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction". The Journal of Experimental Medicine. 151 (5): 1196–1212. doi:10.1084/jem.151.5.1196. ISSN   0022-1007. PMC   2185855 . PMID   6445399.
  2. Nussenzweig, M C; Steinman, R M; Witmer, M D; Gutchinov, B (1 January 1982). "A monoclonal antibody specific for mouse dendritic cells". Proceedings of the National Academy of Sciences of the United States of America. 79 (1): 161–165. Bibcode:1982PNAS...79..161N. doi: 10.1073/pnas.79.1.161 . ISSN   0027-8424. PMC   345682 . PMID   6948298.
  3. "Heads of Laboratory: Michel C. Nussenzweig". The Rockefeller University. Retrieved 16 Aug 2016.
  4. "Immunity and Tolerance". Howard Hughes Medical Institute. Retrieved 16 Aug 2016.
  5. Scheid, Johannes F.; Mouquet, Hugo; Feldhahn, Niklas; Seaman, Michael S.; Velinzon, Klara; Pietzsch, John; Ott, Rene G.; Anthony, Robert M.; Zebroski, Henry; Hurley, Arlene; Phogat, Adhuna; Chakrabarti, Bimal; Li, Yuxing; Connors, Mark; Pereyra, Florencia; Walker, Bruce D.; Wardemann, Hedda; Ho, David; Wyatt, Richard T.; Mascola, John R.; Ravetch, Jeffrey V.; Nussenzweig, Michel C. (2 April 2009). "Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals". Nature. 458 (7238): 636–640. Bibcode:2009Natur.458..636S. doi:10.1038/nature07930. PMID   19287373. S2CID   4399760.
  6. Halper-Stromberg, Ariel; Lu, Ching-Lan; Klein, Florian; Horwitz, Joshua A.; Bournazos, Stylianos; Nogueira, Lilian; Eisenreich, Thomas R.; Liu, Cassie; Gazumyan, Anna; Schaefer, Uwe; Furze, Rebecca C.; Seaman, Michael S.; Prinjha, Rab; Tarakhovsky, Alexander; Ravetch, Jeffrey V.; Nussenzweig, Michel C. (28 August 2014). "Broadly Neutralizing Antibodies and Viral Inducers Decrease Rebound from HIV-1 Latent Reservoirs in Humanized Mice". Cell. 158 (5): 989–999. doi:10.1016/j.cell.2014.07.043. PMC   4163911 . PMID   25131989.
  7. Scheid, Johannes F.; et al. (28 July 2016). "HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption". Nature. 535 (7613): 556–560. Bibcode:2016Natur.535..556S. doi:10.1038/nature18929. PMC   5034582 . PMID   27338952.
  8. Lu, Ching-Lan; Murakowski, Dariusz K.; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A.; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V.; Caskey, Marina; Chakraborty, Arup K.; Nussenzweig, Michel C. (20 May 2016). "Enhanced clearance of HIV-1–infected cells by broadly neutralizing antibodies against HIV-1 in vivo". Science. 352 (6288): 1001–1004. Bibcode:2016Sci...352.1001L. doi:10.1126/science.aaf1279. ISSN   0036-8075. PMC   5126967 . PMID   27199430.
  9. Schoofs, Till; Klein, Florian; Braunschweig, Malte; Kreider, Edward F.; Feldmann, Anna; Nogueira, Lilian; Oliveira, Thiago; Lorenzi, Julio C. C.; Parrish, Erica H.; Learn, Gerald H.; West, Anthony P.; Bjorkman, Pamela J.; Schlesinger, Sarah J.; Seaman, Michael S.; Czartoski, Julie; McElrath, M. Juliana; Pfeifer, Nico; Hahn, Beatrice H.; Caskey, Marina; Nussenzweig, Michel C. (20 May 2016). "HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1". Science. 352 (6288): 997–1001. Bibcode:2016Sci...352..997S. doi:10.1126/science.aaf0972. ISSN   0036-8075. PMC   5151174 . PMID   27199429.
  10. "AAI-Thermo Fisher Meritorious Career Award" . Retrieved 14 July 2016.
  11. "Twelve Howard Hughes Medical Institute Scientists Elected to American Academy of Arts and Sciences". Howard Hughes Medical Institute. Retrieved 15 August 2016.
  12. "Past Howley Prize Recipients" . Retrieved 18 July 2016.
  13. "Institute of Medicine Elects 65 New Members, Five Foreign Associates". News from The National Academies. Retrieved 15 August 2016.
  14. "Michel C. Nussenzweig elected to National Academy of Sciences". 3 May 2011. Retrieved 16 August 2016.
  15. "Eleitos novos membros da ABC" [Newly Elected Members of the ABC] (in Portuguese). 16 December 2011. Retrieved 14 July 2016.
  16. "Nobel Lecture 2011". The Official Site of the Nobel Prize. Retrieved 18 September 2022.
  17. "Prêmio Diáspora Brasil divulga vencedores" (in Portuguese). Retrieved 16 August 2016.
  18. "Toma de Posesión de Académico de Honor del Excmo. Sr. D. Michel C. Nussenzweig". Real Academia Nacional de Farmacia (in Spanish). 11 April 2016. Retrieved 16 August 2016.
  19. "The 2016 Rabbi Shai Shacknai Memorial Lecture in Immunology and Cancer Research" (PDF). The Hebrew University of Jerusalem Faculty of Medicine. Retrieved 16 August 2016.
  20. "With their outstanding research, laureates lay the foundation for understanding the way in which different immunological mechanisms function". 22 June 2016. Retrieved 18 July 2016.
  21. "AAI-BioLegend Herzenberg Award Past Recipients". The American Association of Immunologists. Retrieved 7 March 2018.
  22. "JEM Editorial Board Co-Chair wins 2017 Sanofi-Institut Pasteur Award". Journal of Experimental Medicine. 12 December 2017. Retrieved 5 March 2018.