Oscar Negrete, Ph.D.

Dr. Negrete's research interests lie in characterizing the entry mechanisms of highly pathogenic zoonotic viruses. Nipah virus (NiV) is an emerging virus with one of the highest mortality rates in humans (˜ 75%) and a broad host range that extends to livestock. Rift Valley fever virus (RVFV) is a mosquito–borne pathogen that primarily affects livestock, but can also cause lethal hemorrhagic fever and encephalitis in humans. Having discovered the cell receptors required for Nipah virus entry into cells, his research continues to focus on identifying new determinants of viral entry for NiV and RVFV. A current topic of study includes using genome–wide RNA interference screening to identify novel host factors and pathways involved in RVFV entry. His research uses a broad spectrum of biochemical, cellular, molecular biology, and immunological techniques to dissect membrane fusion and entry mechanisms. Viral entry studies are anticipated to assist in the formulation of new therapeutic, vaccine and diagnostics for Nipah virus and Rift valley fever virus.

Appointments

Education

Current Research Projects at Sandia

Publications:

Harmon B, Kozina C, Maar D, Carpenter T, Branda C, Negrete OA, Carson B. (2013). Identification of Critical Amino Acids within the Nucleoprotein of Tacaribe virus important for anti-interferon activity. Journal of Biological Chemistry. 288(12):8702-8711.

Schudel B, Harmon B, Abhyankar V, Pruitt B, Negrete OA, Singh A. (2013) Microfluidic platforms for RNA interference screening of virus–host interactions. Lab on a Chip. 13:811-817.

Harmon B, Schudel B, Maar D, Kozina C, Ikegami T, Tseng C, Negrete OA. (2012) Rift Valley Fever virus strain MP–12 enters mammalian host cells via caveolae mediated endocytosis. Journal of Virology. 86(23):12954-12970.

Maar D, Harmon B, Chu D, Shultz B, Aguilar HC, Lee B, Negrete OA. (2012) Cysteines in the stalk domain of the Nipah virus G glycoprotein are located in a distinct subdomain critical for fusion activation. Journal of Virology. 86(12):6632-42.

Wolf, MC, AN Freiberg, T Zhang, ZA Ataman, J Li, PW Hong, AC Aguilar, A Grock, AN Honko, J Johnson, M Porotto, R Damoiseaux, J Miller, OA Negrete, P Krogstad, A Moscona, LE Hensley, SP Whelan, MR Holbrook, ME Jung, B Lee. (in press). A broad–spectrum antiviral targeting enveloped viruses. Proceedings of the National Academy of Sciences.

Aguilar, HC, ZA Ataman, V Aspericueta, AQ Fang, M Stroud, OA Negrete, RA Kammerer, B Lee. (2009). Receptor-induced activation of the Nipah virus attachment glycoprotein (G) that triggers the fusion glycoprotein (F). Journal of Biological Chemistry 284:1628.

Negrete, OA, D Chu, HC Aguilar, B Lee. (2007). Single amino acid changes in the Nipah and Hendra virus attachment glycoprotein distinguishes ephrinB2 from ephrinB3 usage. Journal of Virology 81:10804.

Negrete, OA*, MC Wolf *, B Lee. (2007). The pathobiology of henipavirus entry: Insights into therapeutic strategies. Future Virology 2:267. *Contributed equally.

Aguilar, HC, KA Matreyek, CM Filone, ST Hashimi, EL Levroney, OA Negrete, A Bertolotti–Ciarlet, DY Choi, I McHardy, JA Fulcher, SV Su, MC Wolf, L Kohatsu, LG Baum, B Lee. (2006). N-glycans on Nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry. Journal of Virology 80:4878.

Negrete, OA, MC Wolf, HC Aguilar, S Enterlein, W Wang, E Muhlberger, SV Su, A Bertolotti–Ciarlet, R Flick, B Lee. (2006). Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathogenesis 2:e7.

Negrete, OA, EL Levroney, HC Aguilar, A Bertolotti–Ciarlet, R Nazarian, S Tajyar, B Lee. (2005). EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus. Nature 436:401.

Su, SV, P Hong, S Baik, OA Negrete, KB Gurney, B Lee. (2004). DC–SIGN binds to HIV–1 glycoprotein 120 in a distinct but overlapping fashion compared with ICAM–2 and ICAM–3. Journal of Biological Chemistry 279:19122.

Patents:

Lee, B, OA Negrete. Henipavirus receptor and uses thereof. Patent Application WO/2007/005244. June16, 2006.

Perroud T, Renzi R, Negrete O, Claudnic MR. A Microelectroporation device for genomic screening. U.S. Patent Application 13/173,180. June 31, 2011.

Ashely C, Brinker CJ, Carnes EC, Fekrazad MH, Felton LA, Negrete O, Padilla DP, Wilkinson BS, Wilkinson DC, Willman CL. Porous nanoparticle–supported lipid bilayers (protocells) for targeted delivery including transdermal delivery of cargo and methods thereof. International Patent Application PCT/US12/60072. October 12, 2012.

Contact Information:

Dr. Oscar A. Negrete
Biotechnology and Bioengineering Department
Sandia National Laboratories
PO Box 969, MS 9292
Livermore, CA 94551-0969