Scripps Research Joint Appointments

Assistant Professor, Department of Integrative Structural and Computational Biology

Research Focus

Applying computational biology and bioinformatics to fundamental and translational research.
Our lab is interested in developing computational and bioinformatics methodologies to address a wide range of questions in emerging areas of biological and medical research. The hypotheses generated by theoretical prediction and computation are validated experimentally within the lab and through collaborations with other labs.

Current efforts in the lab focus on three areas:

Vaccine development. We develop computational tools for next-generation sequencing (NGS) analysis of antibody repertoires and structure-based immunogen design. Equipped with newly developed antibodyomics tools, we seek to understand the mechanism of antibody maturation, to identify broadly neutralizing antibodies (bnAbs) from patient samples, and to optimize antibody function for therapeutic purpose. In parallel, structural modeling tools are employed to analyze antibody-antigen complexes and to design novel immunogens (and probes) for HIV-1, Flu and other pathogens. The antibodies identified from NGS analysis and designed immunogens will be characterized experimentally.

Structure-function study of molecular complexes. We develop and apply computational tools to study large molecular machines such as viruses, enzyme complexes, transporters and ion channels. One of our major focuses is to develop a computational platform for building, refining, modeling and analyzing atomic structures of these complexes using cryo-electron microscopy (cryo-EM) density map and other structural measurements (e.g. smFRET) as experimental constraint. In doing so, we implement new computational tools based on a vast repository of techniques developed in the context of protein structure prediction and structural bioinformatics. Current complexes of interest include but are not limited to HIV-1 viral spike and transient receptor channels.

Optical control of neural circuits. We seek to develop novel strategies and to engineer novel protein devices to optically manipulate signaling pathways and neural circuits implicated in neurodegenerative diseases. We are particularly interested in the genetically-encoded optical control of ion channels such as glutamate receptors and calcium channels that play critical roles in these pathways and circuits. Since the success of such control relies on a handful of photo-active proteins found in nature, for example, LOV2, PYP and PHR-CIBN, which have not been fully understood nor optimized for their functions, our lab also seeks to investigate the structure-function relationship of these proteins as well as to engineer, optimize and design new optical proteins.

Education

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

Professional Experience

Research Associate, Howard Hughes Medical Institute and Columbia University, 2002-2009
Staff Scientist, Vaccine Research Center, National Institutes of Health, 2009-2013

Awards & Professional Activities

NIAID, Merit Award - 2010, 2011, 2012

Selected References

Zhou, T.^†, Zhu, J.^†, Wu, X., Moquin, S., Zhang, B., Acharya, P., Georgiev, I., Altae-Tran, H.R., Chuang, G.Y., Joyce, M.G., Kwon, Y.D., Longo, N.S., Louder, M.K., Luongo, T., McKee, K., Schramm, C.A., Skinner, J., Yang, Y., Yang, Z., Zhang, Z., Zheng, A., Bonsignori, M., Haynes, B.F., Scheid, J.F., Nussenzweig, M.C., Simek, M., Burton, D.R., Koff, W.C., Millikin, J.C., Connors, M.C., Shaipro, L., Nabel, G.J., Mascola, J.R., and Kwong, P.D. (^†Co-first authors)
(2013) B cell ontogeny of a highly effective class of HIV-1 neutralizing antibodies. Immunity, Accepted.

Zhu, J., Ofek, G., Yang, Y.P., Zhang, B.S., Louder, M.K., Lu, G.L., McKee, K., Pancera, M., Skinner, J., Zhang, Z.H., Park, R., Eudailey, J., Lloyd, K.E., Blinn, J., Alam, S.M., Haynes, B.F., Simek, M., Burton, D.R., Koff, W.A., Mullikin, J.C., Mascola, J.R., Shapiro, L., and Kwong, P.D. (2013) Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains. Proc. Natl. Acad. Sci. USA., 2013 
Mar 27. [Epub ahead of print].

Zhu, J., Doria-Rose, N., Ofek, G., Pancera, M., Zhang, B.S., Mullikin, J.C., Burton, D.R., Koff, W.C., Shapiro, L., Mascola, J.R., Kwong, P.D. (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, B.S., Georgiev, I., Wang, C., Chen,, X.J., Longo, N.S., Louder, M., McKee, K., O’Dell, S., Perfetto, S., Schmidt, S.D., Shi, W., Wu, L., Yang, Y.P., Yang, Z.Y., Zhang, Z.H., Bonsignori, M., Crump, J.A., Kapiga, S.H., Noel, S.E., Haynes, B.F., Simek, M., Burton, D.R., Koff, W.C., Doria-Rose, N., Connors, M., Mullikin, J., Nabel, G.J., Roederer, M., Shapiro, L., Kwong, P.D., Mascola, J.R.. (^†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, M.H., Li, M.H., Isacoff, E.Y., 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, Z.H., 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.