Department of Immunology and Microbiology
Associate Professor, Department of Integrative Structural and Computational Biology
Applying computational and experimental approaches to translational research.
Our lab is interested in developing and applying computational as well as experimental methods to address a wide range of questions in emerging areas of biomedical research. The hypotheses generated by prediction and computation are validated experimentally within the lab and through collaborations with other labs.
Current efforts in the lab focus on three areas:
Antibody discovery and vaccine design. We develop next-generation sequencing (NGS) technologies and computational tools to facilitate antibody discovery, B cell repertoire analysis, and rational vaccine design. By combining scFv phage library and long-read NGS, we identify functional antibodies for diverse viral targets such as HIV-1, RSV, and ZIKA. Using unbiased repertoire analysis, we investigate the developmental pathways of broadly neutralizing antibodies (bNAbs) during natural infection and vaccination. Structural modeling and nanoparticle engineering are employed to design novel immunogens for vaccine development.
Optical control of neural circuits. We develop novel strategies and engineer protein devices for the optical control of signaling pathways and neural circuits implicated in neurodegenerative diseases. We are particularly interested in genetically-encoded optical control of ion channels such as glutamate receptors and calcium channels, which play critical roles in our nervous system and other body functions. We engineer and optimize photo-active proteins such as LOV2, PYP, and PHR-CIBN to facilitate the light control of these complex molecular machines.
Structure-function study of molecular complexes. We develop and apply computational tools to study macromolecular assemblies such as viruses, enzyme complexes, transporters, and ion channels. One of our major focuses is to develop a computational platform for building and refining atomic structures of these complexes using cryo-electron microscopy (cryo-EM) density map and other structural measurements (e.g. smFRET) as experimental constraints.
B.S., Biology, University of Science and Technology of China, 1998
Ph.D., Computational Biology and Computational Chemistry, University of Science and Technology of China, 2002
Research Associate, Howard Hughes Medical Institute and Columbia University, 2002-2009
Staff Scientist, Vaccine Research Center, National Institutes of Health, 2009-2013
Assistant Professor, The Scripps Research Institute, 2013-2016
NIAID, Merit Award - 2010, 2011, 2012
Morris CD, Azadnia P, de Val N, Vora N, Honda A, Giang E, Saye-Francisco K, Cheng Y, Lin X, Mann CJ, Tang J, Sok D, Burton DR, Law M, Ward AB, He L*, and Zhu J*. (*Co-corresponding authors) (2017) Differential antibody responses to conserved HIV-1 neutralizing epitopes in the context of multivalent scaffolds and native-like gp140 trimers. mBio 8(1):e00036-17.
He L, de Val N, Morris CD, Vora N, Thinnes TC, Kong L, Azadnia P, Sok D, Zhou B, Burton DR, Wilson IA, Nemazee D, Ward AB, and Zhu J. (2016) Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles. Nat. Commun. 7:12041.
Kong L, He L, de Val N, Vora N, Morris CD, Azadnia P, Sok D, Zhou B, Burton DR, Ward AB, Wilson IA, and Zhu J. (2016) Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat. Commun. 7:12040.
Kong L, Ju B, Chen Y, He L, Ren L, Liu J, Hong K, Su B, Wang Z, Ozorowski G, Ji X, Hua Y, Chen Y, Deller MC, Hao Y, Feng Y, Garces F, Wilson R, Dai K, O'Dell S, McKee K, Mascola JR, Ward AB, Wyatt RT, Li Y, Wilson IA, Zhu J*, and Shao Y*.(*Co-corresponding authors) (2016) Key gp120 glycans pose roadblocks to the rapid development of VRC01-class antibodies in an HIV-1-infected Chinese donor. Immunity 44, 939-950 (Cover).
Dai K, He L, Khan SN, O'Dell S, McKee K, Tran K, Li Y, Sundling C, Morris CD, Mascola JR, Hedstam GBK, Wyatt RT, and Zhu J. (2015) Rhesus macaque B-cell responses to an HIV-1 trimer vaccine revealed by unbiased longitudinal repertoire analysis. mBio 6(6):e01375-15.
He L, CHeng Y, Kong L, Azadnia P, Giang E, Kim J, Wood MR, Wilson IA, Law M, and Zhu J. (2015). Approaching rational epitope vaccine design for hepatitis C virus with meta-server and multivalent scaffolding. Sci. Rep. 5, 12501.
He L and Zhu J. (2015). Computational tools for epitope vaccine design and evaluation. Curr. Opin. Virol. 11:103-112.
He L, Sok D, Azadnia P, Hsueh J, Landais E, Simek M, Koff WC, Poignard P, Burton DR, and Zhu J. (2014). Toward a more accurate view of human B-cell repertoire by next-generation sequencing, unbiased repertoire capture and single-molecule barcoding. Sci. Rep. 4:6778.
van Doremalen N, Miazgowicz K, Milne-Price S, Bushmaker T, Robertson S, Scott D, Kinne J, McLellan J, Zhu J, and Munster V. (2014). Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through its Receptor Dipeptidyl Peptidase 4. J. Virol. 88 (16): 9220-32.
Xie J, Yea K, Zhang HK, Moldt B, He LL, Zhu J and Lerner R. (2014). Prevention of Cell Death by Antibodies Selected from Intracellular combinatorial Libraries. Chem Biol., 21: 274-283 (Cover).
Zhu J, Wu, X, Zhang B, McKee K, O'Dell S, Soto C, Zhou T, Casazza JP; NISC Comparative Sequencing Program, Mullikin JC, Kwong PD, Mascola JR, Shaprio L. (2013). De Novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts. Proc Natl Acad Sci USA, 110(43):E4088-97.
Zhou T†, Zhu J†, Wu X, Moquin S, Zhang B, Acharya P, Georgiev I, Altae-Tran HR, Chuang GY, Joyce MG, Kwon YD, Longo NS, Louder MK, Luongo T, McKee K, Schramm CA, Skinner J, Yang Y, Yang Z, Zhang Z, Zheng A, Bonsignori M, Haynes BF, Scheid JF, Nussenzweig MC, Simek M, Burton DR, Koff WC, Millikin JC, Connors MC, Shaipro L, Nabel GJ, Mascola JR, and Kwong PD. (†Co-first authors) (2013). Multidonor analysis reveals structural elements, genetic determinants, and naturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity, 39(2):245-58.
Zhu J, Ofek G, Yang YP, Zhang BS, Louder MK, Lu GL, McKee K, Pancera M, Skinner J, Zhang ZH, Park R, Eudailey J, Lloyd KE, Blinn J, Alam SM, Haynes BF, Simek M, Burton DR, Koff WA, Mullikin JC, Mascola JR, Shapiro L, and Kwong PD. (2013). Mining the antibodyome for HIV-1-neutralizing antibody with next-generation sequencing and phylogenetic pairing of heavy/light chains. Proc. Natl. Acad. Sci. USA., 110(16):6470-5.
Zhu J, Doria-Rose N, Ofek G, Pancera M, Zhang BS, Mullikin JC, Burton DR, Koff WC, Shapiro L, Mascola JR, Kwong PD. (2012). A population of PGT135-137-related broadly neutralizing HIV-1 antibodies identified by 454-pyrosequencing and bioinformatics. Front. Microbiol., 3:315.
Wu X†, Zhou T†, Zhu J†, Zhang BS, Georgiev I, Wang C, Chen XJ, Longo NS, Louder M, McKee K, O’Dell S, Perfetto S, Schmidt SD, Shi W, Wu L, Yang YP, Yang ZY, Zhang ZH, Bonsignori M, Crump JA, Kapiga SH, Noel SE, Haynes BF, Simek M, Burton DR, Koff WC, Doria-Rose N, Connors M, Mullikin J, Nabel GJ, Roederer M, Shapiro L, Kwong PD, Mascola JR. (†Co-first authors) (2011). Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science, 333 (6049):1593-602 (Cover).
Zhu J†, Yu Y†, Ulbrich MH, Li MH, Isacoff EY, Honig B, Yang J. (†Co-first authors) (2011). Structural model of the TRPP2/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach. Proc. Natl. Acad. Sci. USA., 108 (25): 10133-10138.
Zhu J, Cheng L, Fang Q, Zhou ZH, Honig B. (2010). Building and refining protein models within cryo-electron microscopy density maps based on homology modeling and multi-scale structure refinement. (Cover) J. Mol. Biol., 397 (3):835-851.