Adolfo Garcia-Sastre, PhD
- DIRECTOR GLOBAL HEALTH AND EMERGING PATHOGENS INSTITUTE
- PROFESSOR | Medicine, Infectious Diseases
- PROFESSOR | Microbiology
Research Topics:Antivirals, Biodefense, Cellular Immunity, Cytokines, Gene Expressions, Gene Regulation, Gene Therapy, Immune Antagonism, Infectious Disease, Influenza Virus, Interferon, Interferon Antagonists, Interferon Resistance, Molecular Biology, Paramyxovirus, RNA, RNA Splicing & Processing, RNA Transport & Localization, Trafficking, Transcription Factors, Transcriptional Activation and Repression, Vaccine Development, Virulence Genes, Viruses and Virology
Dr. Garcia-Sastre is Professor in the Department of Microbiology and Director of the Global Health & Emerging Pathogens Institute at Mount Sinai School of Medicine in New York. He is also Principal Investigator for the Center for Research on Influenza Pathogenesis (CRIP), one of five NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS). Together with Charlie Rice, he is the leader of the basic research component on Viral Therapeutics and Pathogenesis of the North East Biodefense Center proposal, which was funded by NIAID and involves the collaboration of more than 20 academic institutions in New York, Connecticut and New Jersey.
For the past 20 years, his research interest has been focused on the molecular biology of influenza viruses and several other negative strand RNA viruses. During his postdoctoral training in the early 1990s, he developed for the first time, novel strategies for expression of foreign antigens by a negative strand RNA virus, influenza virus. He has made major contributions to the influenza virus field, including 1) the development of reverse genetics techniques allowing the generation of recombinant influenza viruses from plasmid DNA (studies in collaboration with Dr. Palese); 2) the generation and evaluation of influenza virus vectors as potential vaccine candidates against different infectious diseases, including malaria and AIDS; 3) the identification of the biological role of the non structural protein NS1 of influenza virus during infection: the inhibition of the type I interferon (IFN) system; and 4) the reconstruction and characterization of the extinct pandemic influenza virus of 1918. His studies provided the first description and molecular analysis of a viral-encoded IFN antagonist among negative strand RNA viruses. These studies led to the generation of attenuated influenza viruses containing defined mutations in their IFN antagonist protein that might prove to be optimal live vaccines against influenza. His research has resulted in more than 100 scientific publications and reviews. He was among the first members of the Vaccine Study Section of the NIH.
In addition, he is an editor for Journal of Experimental Medicine and PLoS Pathogens and a member of the Editorial Board of Journal of Virology, Virology, Journal of General Virology and Virus Research. He has been a co-organizer of the international course on Viral Vectors (2001), held in Heidelberg, Germany, sponsored by Federation of European Biochemical Societies (FEBS), and of the first Research Conference on Orthomyxoviruses in 2001, held in Teixel, The Netherlands, sponsored by the European Scientific Working Group on Influenza(ESWI).
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Multi-Disciplinary Training AreasGenetics and Genomic Sciences [GGS], Immunology [IMM], Microbiology [MIC]
PhD, University of Salamanca
The Garcia-Sastre Laboratory is focused on exploring virus-host interactions with emphasis on virus regulation of innate and adaptive immune responses. The outcome of these interactions not only determines disease severity but also influences the development of protective immunity resulting from viral infection and/or vaccination. The team has developed several techniques (reverse genetics), which allow for the genetic manipulation of the genomes of several virus families including influenza virus and Newcastle disease virus. Other viruses being studied include Dengue virus, West Nile virus, and Crimean-Congo hemorrhagic fever virus. These techniques are currently being used in several research areas including: i) characterization of virus-encoded virulence factors, ii) identification of virus-encoded antagonists of the interferon system, iii) virus replication and gene expression, iv) immune regulation of influenza replication, and v) vaccine development.
Reverse genetics are also being utilized to generate virus vectors based on influenza virus and Newcastle disease virus. These viruses are effective inducers of humoral and cellular immune responses. Live attenuated influenza virus vaccines are being generated by genetic modification of the influenza virus-encoded interferon antagonist that was originally identified by the laboratory. Also, recombinant viruses can be produced that express protective antigens of other pathogens for which no safe attenuated vaccine strains are available.
FRIAS-STAHELI N, GIANNAKOPOULOS NV, KIKKERT M, TAYLOR S, BRIDGEN A, PARAGAS JJ, RICHT JA, ROWLAND RR, SCHMALJOHN CS, LENSCHOW DJ, SNIJDER EJ, GARCIA-SASTRE A, VIRGIN IV HW. Ovarian tumor (OTU)-domain containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell, Host and Microbe 2007; 2: 404-416.
VIGIL A, PARK MS, MARTINEZ O, CHUA MA, XIAO S, CROS JF, MARTINEZ-SOBRIDO L, WOO SC, GARCIA-SASTRE A. Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus. Cancer Research 2007; 67: 8285-8292.
MIBAYASHI M, MARTINEZ-SOBRIDO L, LOO YM, CARDENAS WB, GALE JR M, GARCIA-SASTRE A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. Journal of Virology 2007; 81: 514-524.
RICHT JA, LEKCHAROENSUK P, LAGER KM, VINCENT AL, LOIACONO CM, JANKE BH, WU WH, YOON KJ, WEBBY RJ, SOLORZANO A, GARCIA-SASTRE A. Vaccination of pigs against swine influenza viruses using an NS1-truncated modified live virus vaccine. Journal of Virology 2006; 80: 11009-11018.
TUMPEY TM, MAINES TR, VAN HOEVEN N, GLASER L, SOLORZANO A, PAPPAS C, COX NJ, SWAYNE DE, PALESE P, GARCIA-SASTRE A. A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 2007; 315: 655-659.
TUMPEY TM, BASLER CF, AGUILAR PV, ZENG H, SOLORZANO A, SWAYNE DE, COX NJ, KATZ JM, TAUBENBERGER JK, PALESE P, GARCIA-SASTRE A, . Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005; 310: 77-80.
MUNOZ-JORDAN J, SANCHEZ-BURGOS GG, LAURENT-ROLLE M, GARCIA-SASTRE A. Inhibition of interferon signaling by dengue virus. Proceedings of the National Academy of Sciences (U.S.A.) 2003; 100: 14333-14338.
BASLER CF, REID AH, DYBING JK, JANCZEWSKI TA, FANNING TG, ZHENG H, SALVATORE M, PERDUE ML, SWAYNE DE, GARCIA-SASTRE A, PALESE P, TAUBENBERGER JK. Sequence of the 1918 pandemic influenza virus non-structural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proceedings of the National Academy of Sciences (U.S.A.) 2001; 98: 2746-2751.
GARCIA-SASTRE A, . Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative strand RNA viruses. Virology 2001; 279: 375-384.
FODOR E, DEVENISH L, ENGELHARDT OG, PALESE P, BROWNLEE GG, GARCIA-SASTRE A. Rescue of influenza A virus from recombinant DNA. Journal of Virology 1999; 73: 9679-9682.