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Integrative Structural and Computational Biology

Jiang Zhu, PhD

Associate Professor
Department of Integrative Structural and Computational Biology
California Campus
Laboratory Website
jiang@scripps.edu
(858) 784-8157

Scripps Research Joint Appointments

Associate Professor with Tenure, Department of Immunology and Microbial Science
Associate Professor with Tenure, Department of Integrative Structural and Computational Biology
Faculty, Graduate Program

Other Joint Appointments

Texas Biomedical Research Center

Research Focus

We combine computational and experimental approaches to address critical questions in biomedical research. The hypotheses generated through reasoning and modeling are validated experimentally in our laboratory and through collaborations. The goal of our research is provide innovative solutions to disease prevention and therapeutics.

Antibody discovery and vaccine design. We develop next-generation sequencing (NGS) technologies and computational tools to facilitate antibody discovery, B-cell repertoire analysis, and vaccine evaluation.  By combining scFv phage library and 900bp 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 monitor the vaccine-induced B-cell response in animal and human trials.  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.

For interested postdoctoral candidates, please send your application package to Dr. Zhu by email. Prior experience in structural biology, immunology, vaccine research, and oncology will be a big plus. 

Education

B.S., Biology, University of Science and Technology of China, 1998
Ph.D., Computational Biology, University of Science and Technology of China, 2002

Professional Experience

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

Associate Professor, The Scripps Research Institute, 2017-2020

Assocate Professor with Tenure, The Scripps REsearch Institute, 2020 - present

Awards & Professional Activities

NIAID, Merit Award - 2010, 2011, 2012

Selected References

Zhang Y-N, Paynter J, Sou C, Fourfouris T, Wang Y, Abraham C, Ngo T, Zhang Y, He L, Zhu J. (2021) Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants. Sci. Adv. 7:eabj3107.

Kumar S, Lin X, Ngo T, Shapero B, Sou C, Allen JD, Copps J, Zhang L, Ozorowski G, He L, Crispin M, Ward AB, Wilson IA*, Zhu J*. (*Co-corresponding authors) (2021) Neutralizing antibodies induced by first-generation gp41-stabilized HIV-1 envelope trimers and nanoparticles. mBio 12:e00429-21.

He L, Chaudhary A, Lin X, Sou C, Alkutkar T, Kumar S, Ngo T, Kosviner E, Ozorowski G, Stanfield RL, Ward AB, Wilson IA*, Zhu J*. (*Co-corresponding authors) (2021) Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines. Nat. Commun. 12:2633.

He L, Lin X, Wang Y, Abraham C, Sou C, Ngo T, Zhang Y, Wilson IA, Zhu J. (2021) Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates. Sci. Adv. 7:eabf1591.

Chen F, Tzarum N, Lin X, Giang E, Velázquez-Moctezuma R, Augestad E, Nagy K, He L, Hernandez M, Fouch ME, Grinyó A, Chavez D, Doranz BJ, Prentoe J, Stanfield RL, Lanford R, Bukh J, Wilson IA*, Zhu J*, Law M*. (*Co-corresponding authors) (2021) Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins. Immunity 54:1-16.

Kumar S, Ju B, Shapero B, Lin X, Ren L, Zhang L, Li D, Zhou Z, Feng Y, Sou C, Mann CJ, Hao Y, Sarkar A, Hou J, Nunnally C, Hong K, Wang S, Ge X, Su B, Landais E, Sok D, Zwick MB, He L, Zhu J*, Wilson IA*, Shao Y*. (*Co-corresponding authors) (2020) A VH1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite. Sci. Adv. 6:eabb1328.

Wen GP, He L, Tang ZM, Wang SL, Zhang X, Chen YZ, Lin X, Liu C, Chen JX, Ying D, Chen ZH, Wang YB, Luo WX, Huang SJ, Li SW, Zhang J, Zheng ZZ*, Zhu J*, Xia NS*. (*Co-corresponding authors) (2020) Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans. Nat. Commun. 11:3971.

He L , Tzarum N, Lin X, Shapero B, Sou C, Mann CJ, Stano A, Zhang L, Nagy K, Giang E, Law M*, Wilson IA*, Zhu J*. (*Co-corresponding authors) (2020) Proof-of-concept for rational design of hepatitis C virus E2 core nanoparticle vaccines. Sci. Adv. 6:eaaz6225.

Chen F, Nagy K, Chavez D, Willis S, Mcbride R, Giang E, Honda A, Bukh J, Ordoukhanian P, Zhu J, Frey S, Lanford R, Law M. (2019) Antibody Responses to Immunization With HCV Envelope Glycoproteins as a Baseline for B cell-based Vaccine Development. Gastroenterology pii: S0016-5085(19)41871-4.

Zhang L, Irimia A, He L, Landais E, Rantalainen K, Leaman DP, Vollbrecht T, Stano A, Sands DI, Kim AS, IAVI Protocol G Investigators, Poignard P, Burton DR, Murrell B, Ward AB, Zhu J*, Wilson IA*, Zwick MB*. (*Co-corresponding authors) (2019) An MPER antibody neutralizes HIV-1 using germline features shared among donors. Nat. Commun. 10, 5389.

Gao F, Lin X, He L, Wang R, Wang H, Shi X, Zhang F, Yin L, Zhang L*, Zhu J*, Yu L*. (*Co-corresponding authors) (2019) Development of a potent and protective germline-like antibody against Zika virus in a convalescent human. Front Immunol 10:2424.

Tzarum N, Giang E, Kong L, He L, Prentoe J, Augestad E, Hua Y, Castillo S, Lauer GM, Bukh J, Zhu J*, Wilson IA*, Law M*. (*Co-corresponding authors) (2019) Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. Sci. Adv. 5:eaav1882.

He L, Kumar S, Allen JJ, Huang D, Lin X, Mann CJ, Saye-Francisco KL, Copps J, Sarkar A, Blizard GS, Ozorowski G, Sok D, Crispin M, Ward AB, Burton DR, Wilson IA*, Zhu J*. (*Co-corresponding authors) (2018) HIV-1 vaccine design through minimizing envelope metastability. Sci. Adv. 4:eaau6769.

He L*, Lin X, de Val N, Saye-Francisco KL, Mann CJ, Augst R, Morris CD, Azadnia P, Zhou B, Sok D, Ozorowski G, Ward AB, Burton DR, Zhu J*. (*Co-corresponding authors) (2017) Hidden lineage complexity of glycan-dependent HIV-1 broadly neutralizing antibodies uncovered by digital panning and native-like gp140 trimer. Front. Immunol. 8:1025.

Xia L, Tang A, Meng W, Freed DC, He L, Wang D, Li F, Li L, Xiong W, Gui X, Schultz RD, CHen H, He X, Swoyer R, Ha S, Liu Y, Morris CD, Zhou Y, Wang I-M, Zhao Q, Luo W, Xia N, Espeseth AS, Hazuda DJ, Rupp RE, Barrett AD, Zhang N, Zhu J*, Fu T*, An Z*.(*Co-corresponding authors) (2017) Active evolution of memory B-cells specific to viral gH/gL/pUL128/130/131 pentameric complex in healthy subjects with silent human cytomegalovirus infection. Oncotarget  8(43):73654-73669

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*, 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*, Zhu J*. (*Co-corresponding authors) (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*, Zhu J*. (*Co-corresponding authors) (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*, 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, 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, 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,  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, 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, 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, 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.