Veterinary Microbiology and Pathology

Hector Aguilar-Carreno

Tenure-Track Assistant Professor
Email: haguilar@vetmed.wsu.edu
509-335-4410

Education and Training

Instituto Tecnologico de Tepic	B.S.	1990	Biochemical Engineering
California State University, Los Angeles	M.S.	1994	Biology
University of Southern California	Ph.D.	2002	Biochemistry and Molecular Biology / Virology
University of California, Los Angeles	Post-Doc	2003-2008	Virus entry mechanisms

Research Interests

Hector Aguilar-Carreno's primary research interest is the elucidation of the mechanisms of entry of enveloped viruses into mammalian host cells. Dr. Aguilar obtained his Ph.D. from the University of Southern California where he studied retrovirus membrane fusion and viral entry. He did his post-doctoral training in Dr. Benhur Lee's laboratory at UCLA, where he co-discovered the henipavirus receptors, and established several new assays to study receptor-mediated Nipah virus entry. He is now an Assistant Professor in the Paul G. Allen School of Global Animal Health and in the Dept. of Veterinary Microbiology and Pathology, and an Associate faculty in the School of Molecular Biosciences at Washington State University. Viral-cell membrane fusion is a crucial step during entry of enveloped viruses into their mammalian host cells. In addition, for some viruses (e.g. some paramyxoviruses), viral infection induces the pathological cell-cell fusion (syncytia). Dr. Aguilar lab uses multidisciplinary approaches to study viral-cell and cell-cell membrane fusion that combine the fields of biochemistry, molecular biology, immunology, and biophysics to focus mainly on the deadly Nipah and Hendra viruses as model systems. The Aguilar lab recently developed new quantitative and kinetic techniques to study how the membrane fusion cascade is "triggered" by viral attachment to the host cell receptors. Dr. Aguilar believes that a combination of multi-disciplinary approaches will lead to antiviral strategies that may be applicable beyond these deadly zoonotic viruses, having profound effects in global human and animal health.

Research and Professional Experience

1992-1994	Research Assistant, Department of Biology and Microbiology, California State University, Los Angeles. Actin Isoform mRNA expression in muscle development. Supervisor: Sandra Sharp.
1993-1994	Teaching Assistant: General Biology, Zoology, Botany, and Genetics. Department of Biology and Microbiology, California State University, Los Angeles.
1994-2002	Research Assistant, Department of Biochemistry and Molecular Biology, University of Southern California, Molecular Biology of Moloney murine leukemia virus fusion in viral entry. Supervisor: Paula Cannon.
2002-2003	Chemistry Instructor, Don Bosco Technical Institute. General Chemistry and Advanced-Placement Chemistry lectures and laboratories.
2003-2008	Post-Doctoral Researcher, Department of Microbiology, Immunology, and Molecular Genetics. University of California, Los Angeles, Nipah virus entry research. Supervisor: Benhur Lee.
2008-2011	Assistant Researcher, Department of Microbiology, Immunology, and Molecular Genetics. University of California, Los Angeles, Nipah virus entry research.
2011-present	Assistant Professor, Paul G. Allen School of Global Animal Health and Department of Veterinary Microbiology and Pathology, School of Molecular Biosciences, Washington State University.
Honors
1990	Graduated with Highest Scholar Honors from Instituto Tecnologico de Tepic.
1992-1994	Research Infrastructure for Minority Institutions Research Award from CSULA.
1993	Foreign Student Joseph Sacher Fellowship. California State University.
1993-1994	California State University Full Foreign Student Scholarship
2007	American Society of Virology Conference Travel Award.
2009	American Society of Virology Conference Travel Award.
2011	Washington State University sole Faculty Nominee - Searle Scholar program.
2011	Washington State University sole Faculty Nominee - Pew Scholars Program in Biomedical Sciences.
2011	Washington State University Faculty Nominee - Mallinckrodt Foundation Scholar program.
2012	Washington State University faculty nominee for Burroughs Welcome Fund – career award.
2012	Distinguished Alumnus Award, Instituto Tecnologico de Tepic, Tepic, Nay., Mexico.
Professional Societies
2005-present	Full member, American Society for Virology.
2010-present	Member, American Society of Microbiology
Service
2012	Reviewer – NIH/NIAID/Virology A panel.
2012	Reviewer – NIH/NIAID/Partnerships for Biodefense panel.

Selected peer-reviewed publications (in chronologic order)

1. Aguilar, H. C., W. French Anderson, and Paula M. Cannon. Cytoplasmic tail of Moloney murine leukemia virus envelope protein influences the conformation of the extracellular domain: implications of mechanisms of action of the R peptide. Journal of Virology, 2003. 77(2):1281-1291.     PMID: 12502845.
2. Aguilar, H. C.*, E. L. Levroney*, J. Fulcher, L. Kohatsu, K. E. Pace, K. B. Gurney, L. G. Baum and B. Lee. Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines. J. Immunology, 2005. 175(1):413-420. PMID: 15972675.
   * Contributed equally.
3. Negrete, O.A., Levroney, E.L.*, Aguilar, H.C.*, Bertolotti-Ciarlet, A.*, Nazarian, R.*, Tajyar, S., Lee, B. EphrinB2 is the entry receptor for Nipah Virus, an emergent deadly paramyxovirus. Nature, 2005. 436(7049):401-405. PMID: 16007075.
   * Contributed equally.
4. Negrete, O.A., Wolf, M., Aguilar, H.C., Enterlein, S., Wang, W., Muhlberger, E., Su, S.V., Bertolotti-Ciarlet, A., Flick, R., Lee, B. Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathogen, 2006. 2(2):78-86.     PMID: 16477309.
5. Aguilar, H.C., K. A. Matreyek, C. M. Filone, E. L. Levroney, A. Bertolotti-Ciarlet, O. Negrete, D. Y. Choi, , I. McHardy, J. A. Fulcher, S. V. Su, M. C. Wolf, L. Kohatsu, S. Tajyar, L. G. Baum, B. Lee. N-glycans on Nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry. Journal of Virology, 2006. 80(10):4878-4889. PMID: 16641279.
6. Schowalter, R. M., Wurth, M. A., Aguilar, H.C., Lee, B., Moncman, C. L., McCann, R. O., Dutch, R. E. Rho-GTPase activity modulates paramyxovirus protein mediated membrane fusion. Virology, 2006. 350(2):323-334. PMID: 16500690.
7. Aguilar, H.C., Matreyek, K. A., Choi, D. Y., Filone, C. M., Young, S., and Lee., B. Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling. Journal of Virology, 2007. 81(9):4520-4532. PMID: 17301148.
8. Negrete, O.A., Chu, D., Aguilar, H.C., B. Lee. Single amino acid changes in the Nipah and Hendra virus attachment glycoprotein distinguishes ephrinB2 from ephrinB3 usage. Journal of Virology, 2007. 81(19):10804-14.     PMID: 17652392.
9. Rozenberg-Adler, Y., Conner, J., Aguilar-Carreno, H.C., Chakraborti, S., Dimitrov, D. S., Anderson, W.F. Membrane-proximal cytoplasmic domain of Moloney murine leukemia virus envelope tail facilitates fusion. Exp. Mol. Pathol., 2008. 84(1):18-30.     PMID: 18222422.
10. Aguilar, H.C.*, Akyol Ataman, Z., Aspericueta, V., Fang, A.Q., Stroud, M., Negrete, O.A., Kammerer, R.A., Lee, B.* A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F). Journal of Biol. Chem., 2009. 284(3):1628-35.     PMID: 19019819.
    * Co-Corresponding authors.
11. Wolf, M.C., Wang, Y., Freiberg, A., Aguilar, H.C., Holbrook, M.R., Lee, B. A catalytically and genetically optimized beta-lactamase-matrix based assay for sensitive, specific, and higher throughput analysis of native henipavirus entry characteristics. Virology Journal, 2009. 6:119. PMID: 19646266.
12. Wolf, M.C., Freiberg, A.N., Zhang, T., Akyol-Ataman, Z., Grock, A., Hong, P.W., Li, J., Watson, N., Fang, A.Q., Aguilar, H.C., Porotto, M., Honko, A.N., Damoiseaux, R., Miller, J.P., Woodson, S.E., Chantasirivisal, S., Fontanes, V., Negrete, O.A., Krogstad, P., Dasgupta, A., Moscona, A., Hensley, L.E., Whelan, S.P., Faull, K.F., Holbrook, M.R., Jung, M.E., Lee, B. "A broad-spectrum antiviral targeting entry of enveloped viruses" PNAS, 2010. 107(7)3157-62.  PMID: 20133606.
13. Garner, O., Aguilar, HC., Fulcher, JA., Levroney, E.L., Harrison, R., Wright, L., Robinson, L., Aspericueta, V., Haslam, S., Dell, A., Lee, B. and Baum, L. Endothelial galectin-1 binding to specific glycans inhibits Nipah virus fusion protein maturation, mobility, and function to block syncytia formation. PLoS Pathogens, 2010. 6(7):e10000993. PMID: 20657665.
14. Aguilar, HC.*, Aspericueta, V., Robinson, L., Aanensen, K., Lee, B. A quantitative and kinetic fusion Protein-Triggering Assay can Discern Distinct Steps in the Nipah Virus Membrane Fusion Cascade. Journal of Virology, 2010. 469(10):8033-8041. PMID: 20519383.
    * Corresponding author.
15. Aguilar HC., Lee, B. Emerging paramyxoviruses: molecular mechanisms and antiviral strategies. Expert Reviews in Mol. Med, 2011. 13:e6. PMID: 21345285.
16. Johnson, J.B., Aguilar, H.C., Lee, B., Parks, G.D. Interaction of human complement with virus particles containing the Nipah virus glycoproteins. Journal of Virology, 2011. 85(12):5940-5948. PMID: 21450814.
17. Mirza, A.M., Aguilar, HC., Zhu, Q., Mahon, P.J., Rota, P.A., Lee, B., and Iorio, R.M. Triggering of the Newcastle disease virus fusion protein by a chimeric attachment protein that binds to Nipah virus receptors. Journal of Biol. Chem. 2011. 286(20):17851-17860. PMID: 21460213.
18. Maar, D., Harmon, B., Chu, D., Schulz, B., Aguilar, H.C, Lee, B., and Negrete, O. Cysteines in the stalk of the Nipah virus G glycoprotein are located in a distinct subdomain critical for fusion activation. Journal of Virology. 2012. 86(12):6632-42. PMID: 22496210.
19. Aguilar, H.C.*, and Lorio, R. Henipavirus membrane fusion and viral entry. Current Topics in Microb. Immun. 2012. In press.
    * Corresponding author.

20. Biering, S., Huang, A., Vu, A., Robinson, L., Choi, E., Lee, B., and Aguilar H.C.* N-glycans in the Nipah virus attachment glycoprotein modulate membrane fusion and protect against neutralization. Journal of Virology. 2012. In press.
    * Corresponding author.

21. Zhu, Q., Biering, S.B., Mirza, A.M., Grasseschi, B.A., Mahon, P.J., Lee, B., Aguilar, H.C., and Iorio, R.M.  Individual N-glycans added at intervals along the stalk of the Nipah virus G protein prevent fusion, but do not block interaction with the homologous F protein. Journal of Virology. 2013. In Press.  

22. Lu, X., Liu, Q., Benavides, J. M., Nicola, A.V., Aston, E., Rasco, B. A., and Aguilar, H.C.*  Detection of receptor-induced glycoprotein conformational changes on enveloped virions using confocal micro-Raman spectroscopy.  Journal of Virology. 2013. In press.    
    * Corresponding author.

23. Vigant, F., Lee, J., Hollmann, A., Tanner, L.B., Akyol Ataman, Z., Yun, T., Shui, G., Aguilar, H.C., Dong, Z., Mariwether, D., Roman-Sosa, G., Robinson, L.R., Juelich, T.L., Buczkowski, H., Chou, S., Castano, M.A., Wolf, M.C., Smith, J.K., Banyard, A., Kielian, M., Reddy, S., Wenk, M.R., Selke, M., Santos, N.C., Freiberg, A.N., Jung, M.E., Lee, B.  A mechanistic paradigm for broad-spectrum antivirals that target virus cell fusion.  PLoS Pathogens. 2013. In press.

Research Support

List selected ongoing or completed (during the last three years) research projects (federal and non-federal support).

Active

R21 AI094329-01 (PI: Hector Aguilar-Carreno)
5 months (calendar)
02/01/12-01/31/14
NIH/NIAID
Dissecting the early steps of the Nipah virus fusion cascade.
This grant explores the early steps of membrane fusion, a process crucial to Nipah virus entry and the pathological induction of cell-cell fusion. The main focus is the dissection of the steps immediately following receptor binding.

R21 AI096103-01 (PI: Anthony V. Nicola, co-I: Hector Aguilar-Carreno)
0.6 months (calendar)
07/01/12-06/30/14
NIH/NIAID
Conformational change in HSV glycoprotein B. This research concerns how the herpesvirus initiates infection in humans by studying the entry of virus into host cells at the molecular level. The project focuses on the role of glycoprotein B in viral entry.

Completed

None