1977: PhD in molecular virology, University of California, Berkeley
1978-80: Post-doctoral research at UCSF with Dr. Christine Guthrie
1980-85: Senior Scientist at MRC Cambridge, UK with Dr. Sydney Brenner.
1985-90: Assistant Member at Scripps Clinics and Res. Foundation with Dr. Michael Oldstone
1990-2000: Faculty at Univ. of WI School of Medicine
2000-present: Professor at Inst of Human Virology, Univ of MD
The Salvato laboratory investigates virus-host interactions using animal models, genomic profiling, and basic molecular virology. Recent studies explored arenavirus pathogenesis using non-human primate models for Lassa fever. Lassa fever vaccine research, has spear-headed by Dr. Lukashevich, has resulted in two live-attenuated candidates: one (ML29) is a reassortant between Lassa virus and Mopeia virus, and the other (YF/LAS) is a recombinant between the Yellow Fever vaccine (YF17D) and the Lassa glycoprotein. The ML29 candidate is broadly cross-reactive and protects primates from Lassa fever. The YF/LAS is effective in protecting guinea pigs but not been tested in primates. Profiling of disease progression during viral hemorrhagic fever has revealed many host-responses that can be detected in blood before viremia is detectable, and that could be prognostic for a virulent as opposed to a benign infection. We are using transcriptomics, proteomics, and metabolomics to profile healthy, diseased and vaccinated primates. The profiles of vaccinated monkeys will provide surrogate markers for successful vaccination. Profiling host responses reveals many recurring themes from virus to virus. For example, interferon-induced pathways are amplified after most viral infections, and most viruses have mechanisms to avoid such anti-viral host responses. Many viruses upset apoptotic pathways, cell cycling and the structures of subcellular macromolecular complexes. Virus infections also alter the motility and physiological location of the infected host cells. In collaboration with Dr. Pauza's laboratory we have explored the role of the Fas/FasL apoptotic pathway in AIDS progression by treating SIV-infected primates with monoclonal antibodies to FasL. Life-time, central memory, and virus-specific cell-mediated immunity are prolonged in the anti-FasL treated animals. The exploration of host responses that restrict virus replication will yield many targets for anti-viral therapy.
Lab Techniques and Equipment:
Biosafety level 2 and biosafety level 3 facilitites house flow cytometer, ultracentrifuges, spectrophotometers, tissue culture incubators and microscopes, PCR machines, gel boxes for protein and nucleic acid analyses, clean stations, biosafety cabinets, blotting and scanning equipment, easy access to animal models.
Grants & Contracts:
Safety of a Lassa vaccine in the context of AIDS
Improving longevity of vaccination by Fas/FasL suppression
Lukashevich IS, PattersonJ, Carrion R, Moshkoff D, Ticer A, Zapata J, Brasky K, Geiger R, Hubbard GB, Bryant J, Salvato MS. 2005 A Live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia Viruses. J Virol 79:13934-13942
Djavani MM, Crasta OR, Zapata JC, Fei Z, Folkerts O, Sobral B, Swindells M, Bryant J, Davis H, Pauza CD, Lukashevich IS, Hammamieh R, Jett M, Salvato MS. 2007. Early blood profiles of virus infection in a monkey model for Lassa Fever. J. Virol. 81: 7960-7973.
Salvato, MS, Yin CC, Yagita H, Maeda T, Okumura K, Tikonov I, Pauza CD. 2007. Attenuated disease in SIV-infected macaques treated with monoclonal antibody against FasL. Clinical and Developmental immunology. Vol 2007: ID#93462, 9 pgs online
Poonia B, Pauza CD, Salvato MS. Role of the Fas/FasL pathway in HIV or SIV disease. Retrovirology. 2009 Oct 15;6:91. Review.
García CC, Topisirovic I, Djavani M, Borden KL, Damonte EB, Salvato MS. 2010. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein. Biochem Biophys Res Commun. 393:625-30.
Zapata JC, Pauza CD, Djavani MM, Rodas JD, Moshkoff D, Bryant J, Ateh E, Garcia C, Lukashevich IS, Salvato MS. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: A model for Lassa fever. Antiviral Res. 2011 92: 125-138.
Goicochea MA, Zapata JC, Bryant J, Davis H, Salvato MS, Lukashevich IS.2012 Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse model. Vaccine. 30:1445-52.
Hayes, MW, Carrion R, Nunneley J, Medvedev Andrey, Salvato MS, Lukashevich IS. 2012. Pathogenic Old World Arenaviruses inhibit TLR2/Mal-dependent pro-inflammatory cytokines in vitro. J Virol. 86:7216-26.
Links of Interest:Dr. Salvato at the Institute of Human Virology
Global Virus Network
Graduate Program in Life Sciences
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