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Oscar Negrete, Ph.D.

Virologist

Biographical Information

Dr. Oscar Negrete is a postdoctoral appointee and the first virologist at Sandia National Laboratories. Dr. Negrete is involved in numerous multidisciplinary projects within the Biosystems Research Department, where he integrates virology research with microfluidic approaches and novel C. elegans host systems. Dr. Negrete recently received a Laboratory Directed Research and Development (LDRD) grant to develop a novel microfluidic high-throughput RNA interference (RNAi) screening platform for studies of genome level virus–host interactions. This LDRD project includes collaborations with the Berkeley Screening Center at the University of California (UC), Berkeley, and the University of Texas Medical Branch (UTMB).

Dr. Negrete received a PhD in microbiology, immunology, and molecular genetics from the University of California, Los Angeles, (UCLA) in 2007. Under the direction of Professor Benhur Lee, Dr. Negrete discovered the host receptors used by the Nipah virus, a highly pathogenic paramyxovirus of biodefense concern. The identification of ephrinB2 and B3 as the Nipah virus receptors provided insight into the wide host range and virulence characteristics of this deadly pathogen. Dr. Negrete’s UCLA research was supported by the Cellular and Molecular Biology Training Grant, the Virology and Gene Therapy Training Grant, and a UCLA Dissertation Year Fellowship. Dr. Negrete began his current postdoctoral appointment at Sandia in 2008.

Current Research Projects at Sandia

Project 1

Developing microfluidic high-throughput screening (HTS) technologies for RNAi studies of virus–host interactions

RNAi technology has recently emerged as a powerful tool to investigate host proteins involved in virus replication on a genome-wide level. However, the interface of the high-throughput equipment necessary to perform such large RNAi screenings becomes problematic when assaying viral pathogens requiring high-level biocontainment. The accessibility of genome-wide RNAi technology is also limited by capital-expense and reagent costs. Therefore, to circumvent issues with current RNAi screening methods, we will develop a microfluidic-based device that combines cellular microarray, cell electroporation, and microfluidic channels to efficiently introduction RNAi libraries into primary cells within a portable and cost-effective platform.

Principal Investigator: Oscar Negrete

Team Members: Thomas Perroud, Brooke Harmon, Ken Sale, and Kent Tseng (UTMB).

Project 2

A C. elegans biosensor host system for virus detection

C. elegans represents a robust and environmentally stable eukaryotic system that is easily genetically manipulated and that is capable of acting as a biosensor. Using reverse-genetic, molecular-virology approaches, we are engineering C. elegans to detect viral pathogens of biodefense concern.

Principal Investigator: Cathy Branda

Team Members: Oscar Negrete, Carrie Kozina, Julie Kasier, Joe Schoeniger, and Mark Tucker

Project 3

A systems biology approach to viral hemorrhagic fever pathogenesis

Hemorrhagic fever viruses are of biodefense and emerging infectious disease concern to researchers involved with biodefense and emerging infectious diseases. Arenaviruses, such as Lassa fever, are thought to induce hemorrhagic disease by altering host-cell signaling, leading to an inappropriate production of pro-inflammatory cytokines. We seek to identify the mechanisms by which viral proteins modulate the host response to arenavirus infection.

Principal Investigator: Bryan Carson

Team Members: Thomas Perroud, Meiye Wu, Oscar Negrete, Cathy Branda, and Norbert Herzog (UTMB)

Recent Publications:

2010

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 novel, potent broad-spectrum antiviral targeting enveloped virus entry. Proceedings of the National Academy of Sciences.

2009

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.

2007

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.

2006

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.

2005

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.

2004

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.

2001

DiGregorio, DA, OA Negrete, A Jeromin, HB Peng, JL Vergara. (2001). Contact-dependent aggregation of functional Ca2+ channels, synaptic vesicles, and postsynaptic receptors in active zones of a neuromuscular junction. European Journal of Neuroscience 14:533.

Patents:

Lee, B, OA Negrete. Henipavirus receptor and uses thereof. U.S. Patent Application WO/2007/005244. June 16, 2006.

Contact Information:

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

onegret@sandia.gov
phone: 925-294-6359
fax: 925-294-3020