Andrew Ward, PhD
Scripps Research Joint Appointments
Research Focus
Investigating membrane proteins and viruses using integrative structural biology techniques
Membrane protein transporters mediate the passage of a wide variety of molecules into and out of the cell. The molecular details underlying the function of most transporters are still unknown. Thus, my group is interested in studying novel membrane proteins using x-ray crystallography, electron microscopy, and other biophysical techniques.
Membrane proteins expressed on the surface of enveloped viruses mediate viral entry into the cell by recognizing cell surface receptors and initiating endocytosis or membrane fusion. Recently, broadly neutralizing antibodies targeting these surface spikes have been shown to provide protection against viruses such as HIV and influenza. We are trying to better understand how these antibodies bind to and neutralize viruses. Using single particle electron microscopy and electron tomography we are able to visualize these complexes and whole viruses, providing information about the mechanism of inhibition and aiding in the design of better immunogens for eliciting a broadly neutralizing antibody response in humans.
Education
Ph.D. (Biology), Scripps Research, 2008B.S. (Biology), Duke University, 2001
Professional Experience
2015-2017 Associate Professor, Integrative Structural and Computational Biology (ISCB), Scripps Research2013-2015 Assistant Professor, Integrative Structural and Computational Biology (ISCB), Scripps Research
2010-2012 Assistant Professor, Molecular Biology, Scripps Research
2008-2010 Research Associate with Dr. Geoffrey Chang, Molecular Biology, Scripps Research
Selected References
Pejchal R., Doores, K.J., Walker, L.M., Khayat, R., Huang, P.S., Wang, S.K., Stanfield, R.L., Julien, J.P., Ramos, A., Crispin M., Depetris R., Katpally, U., Marozsan, A., Cupo, A., Maloveste, S., Liu, Y., McBride, R., Ito, Y., Sanders, R.W., Ogohara, C., Paulsen, J.C., Feizi, T., Scanlan, C.N., Wong, C.H., Moore, J.P., Olson, W.C., Ward A.B., Poignard, P., Schief, W.R., Burton, D.R., Wilson, I.A. (2011) A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. Oct. 13, Epub ahead of print. PMID 21998254.
McClellan, J.S., Pancera, M., Carrico, C., Gorman, J., Julien, J.P., Khayat, R., Louder, R., Pejchal, R., Sastry, M., Dai, K., O’Dell, S., Patel, N., Shahzad-ul-Hussan, S., Yang, Y., Zhang, B., Zhou, T., Zhu, J., Boyington, H.C., Chuang, G.W., Diwanji, D., Georgiev, I., Kwon Y.D., Lee, D., Louder, M.K., Moquin, S., Schmidt, S.D., Yang, Z., Bonsignori, M., Crump, J.A., Kapiga, S.H., Sam, N.E., Haynes, B.F., Burton, D.R., Koff, W.C., Walker, L.M., Phogat, S., Wyatt, R., Orwenyo, J., Wang, L.X., Arthos, J., Bewley, C.A., Mascola, J.R., Nabel, G.J., Schief, W.R., Ward, A.B., Wilson, I.A., Kwong, P.D. (2011) Structure of HIV-1 gp120 V1V2 domain with broadly neutralizing antibody PG9. Nature. Nov. 23, Epub ahead of print. PMID 22113616
Julien J-P, Lee JH, Cupo A, Murin CD, Derking R, Hoffenberg S, Caulfield MJ, King CR, Marozsan AJ, Klasse PJ, Sanders RW, Moore JP, Wilson IA, Ward AB. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Nat Acad Sci U S A 12:4351-4356, 2013. PMCID:PMC3600498.
Kong L, Giang E, Nieusma T, Kadam RU, Cogburn KE, Hua Y, Dai X, Stanfield RL, Burton DR, Ward AB, Wilson IA, Law M. Hepatitis C virus E2 envelope glycoprotein core structure. Science 342:1090-4, 2013 PMCID: PMC3954638
Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, Ekiert DC, Lee JH, Bhabha G, Metlagel Z, Bujny MV, Jongeneelen M, van de Vlugt R, Lamrani M, Korse HJWM, Geelen E, Sahin O, Sieuwerts M, Brakenhoff JPJ, Vogels R, Ii O, Poon LLM, Peiris M, Koudstaal W, Ward AB, Wilson IA, Goudsmit J, Friesen RHE. Highly conserved protective epitopes on influenza B viruses. Science 337:1343-1348, 2012. PMCID: PMC3538841.
Khayat R, Lee JH, Julien JP, Cupo A, Klasse PJ, Sanders RW, Moore JP, Wilson IA, Ward AB. Structural characterization of cleaved, soluble human immunodeficiency virus type-1 envelope glycoprotein trimers. J Virol. 87:9865-72, 2013. PMID: 23824817. PMCID: PMC3754114.
Ward AB, Sali A, Wilson IA. Integrative structural biology. Science 339:913-915, 2013. PMID:
23430643 PMCID: PMC3633482.
Thornburg NJ, Nannemann DP, Blum DL, Besler JA, Tumpey TM, Deshpande S, Fritz GA, Sapparapu G, Krause JC, Lee JH, Ward AB, Lee DE, Li S, Winarski KL, Spiller BW, Meiler J, Crowe JE Jr. Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses. J Clin Invest. 2013. 123:4405-9, 2013 PMCID: PMC3784541.
Tran K, Poulsen C, Guenaga J, de Val Alda N, Wilson R, Sundling C, Li Y, Stanfield RL, Wilson IA, Ward AB, Karlsson Hedestam GB, Wyatt RT. Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign. Proc Natl Acad Sci. 111:E738-47, 2014. PMCID: PMC3932900.
Grover RK, Zhu X, Nieusma T, Jones T, Boero I, MacLeod AS, Mark A, Niessen S, Kim HJ, Kong L, Assas-Garcia N, Kwon K, Chesi M, Smider VV, Salomon DR, Jelinek DF, Kyle RA, Pyles RB, Glass JI, Ward AB, Wilson IA, Lerner RA. A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union. Science 343:656-61, 2014. PMCID: PMC3987992.
Julien, JP, Sok D, Khayat R, Lee JH, Doores KJ, Walker LM, Ramos A, Diwanji DC, Pejchal R, Cupo A, Katpally U, Depetris RS, Stanfield RL, McBride R, Marozsan AJ, Paulson JC, Sanders RW, Moore JP, Burton DR, Poignard P, Ward AB, Wilson IA. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog. 9:e1003342, 2013. PMCID: PMC3642082.
Lyumkis D, Julien J-P, de Val N, Cupo A, Potter CS, Klasse PJ, Burton DR, Sanders RW, Moore JP, Carragher B, Wilson IA, Ward AB. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 Env trimer. Science 342:1484-90, 2013. PMCID: PMC3954647
Blattner C, Lee JH, Sliepen K, Derking R, Falkowska E, de la Pena AT, Cupo A, Julien JP, van Gils M, Lee PS, Peng W, Paulson JC, Poignard P, Burton DR, Moore JP, Sanders RW, Wilson IA, Ward AB. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity 40:669-80, 2014. PMCID: PMC4057017.
Murin CD, Julien J-P, Stanfield R, Sok D, Khayat R, Cupo A, Moore JP, Burton DR, Wilson IA, Ward AB. Structure of 2G12 Fab2 in complex with soluble and fully glycosylated HIV-1 Env by negative-stain single particle electron microscopy. J Virol. 2014. Sep 1;88(17):10177-88. PMID: 24965454
Murin CD, Fusco ML, Bornholdt ZA, Qiu X, Olinger GG, Zeitlin L, Kobinger GP, Ward AB, Saphire EO. Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Nat Acad Sci USA. 2014. Dec. 2;111(48):17182-7.