Jianming Xie, PhD
Faculty Directory

Jianming Xie

Jianming Xie

Assistant Professor of Pharmacology and Pharmaceutical Sciences

Department of Pharmacology and Pharmaceutical Sciences

Jianming Xie received his BS in chemistry from Fudan University, Shanghai, China, in 1997, and MS in organic chemistry from Shanghai Institute of Organic Chemistry, China, in 2000. In his MS research in the laboratory of Prof. Yongzheng Hui and Prof. Biao Yu, he completed the synthesis of a complex natural glycoside using a one-pot, four-glycosylation method. He later switched his interest to chemical biology and moved to the United States in 2001 to pursue a PhD under the guidance of Prof. Peter Schultz at the Scripps Research Institute, La Jolla, California. There, he helped pioneer a novel biosynthetic method to site-specifically incorporate unnatural amino acids into recombinant proteins in E. coli. His work has enabled the design and synthesis of novel protein structures and functions that do not exist in nature.

After receiving his PhD in 2006, he became interested in immunology and joined the laboratory of Prof. Mark Davis as a Cancer Research Institute Irvington postdoctoral fellow at Stanford University. His postdoctoral research integrated the method of site-specific protein modification with fluorescence microscopy and flow cytometry for the study of antigen recognition by T cells. This work revealed ligand-dependent transport of T cell receptors to the immunological synapse, and also led to the development of a protein photochemistry approach to isolate rare, antigen-specific T cells from patient blood samples. In December 2014, he started his lab in the Department of Pharmacology and Pharmaceutical Sciences at the USC School of Pharmacy. His lab combines synthetic peptide chemistry, protein design, cellular engineering and fluorescence microscopy in order to interrogate, engineer and enhance the specificity and efficiency of T cell antigen recognition. The long-term goal is to use the obtained knowledge to guide the design of enhanced immunotherapy and vaccines against cancer, infection and autoimmune diseases.

Areas of Expertise

  • Immune Cell Engineering
  • Immunology
  • Chemical Biology
  • Protein Engineering
  • Cancer Immunotherapy
  • HIV Therapy
  • Immune Monitoring Technologies
  • Education

    The Scripps Research Institute

    PhD

    Shanghai Institute of Organic Chemistry

    MS

    Fudan University

    BS

  • Links
  • Selected Articles

    Targeting HLA-DR loss in hematologic malignancies with an inhibitory chimeric antigen receptor

    Molecular Therapy
    Fan Fei, Liang Rong, Nan Jiang, Alan S. Wayne, and Jianming Xie

    Chimeric antigen receptor natural killer (CAR-NK) cells have remarkable cytotoxicity against hematologic malignancies; however, they may also attack normal cells sharing the target antigen. Since human leukocyte antigen DR (HLA-DR) is reportedly lost or downregulated in a substantial proportion of hematologic malignancies, presumably a mechanism to escape immune surveillance, we hypothesize that the anti-cancer specificity of CAR-NK cells can be enhanced by activating them against cancer antigens while inhibiting them against HLA-DR. Here, we report the development of an anti-HLA-DR inhibitory CAR (iCAR) that can effectively suppress NK cell activation against HLA-DR-expressing cells.

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    A Universal CAR-NK Cell Targeting Various Epitopes of HIV-1 gp160

    ACS Chemical Biology
    Rebecca M. Lim, Liang Rong, Anjie Zhen, and Jianming Xie

    Engineering T cells and natural killer (NK) cells with anti-HIV chimeric antigen receptors (CAR) has emerged as a promising strategy to eradicate HIV-infected cells. However, current anti-HIV CARs are limited by targeting a single epitope of the HIV envelope glycoprotein gp160, which cannot counter the enormous diversity and mutability of viruses. Here, we report the development of a universal CAR-NK cell, which recognizes 2,4-dinitrophenyl (DNP) and can subsequently be redirected to target various epitopes of gp160 using DNP-conjugated antibodies as adaptor molecules.

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    How the immune system talks to itself: the varied role of synapses

    Immunol Rev.
    Jianming Xie, Cristina M. Tato, Mark M. Davis

    Using an elaborately evolved language of cytokines and chemokines as well as cell-cell interactions, the different components of the immune system communicate with each other and orchestrate a response (or wind one down). Immunological synapses are a key feature of the system in the ways in which they can facilitate and direct these responses.

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    Photocrosslinkable pMHC monomers stain T cells specifically and cause ligand-bound TCRs to be 'preferentially' transported to the cSMAC

    Nature Immunology
    Jianming Xie, Johannes B Huppa, Evan W Newell, Jun Huang, Peter J R Ebert, Qi-Jing Li & Mark M Davis

    The binding of T cell antigen receptors (TCRs) to specific complexes of peptide and major histocompatibility complex (pMHC) is typically of very low affinity, which necessitates the use of multimeric pMHC complexes to label T lymphocytes stably. We report here the development of pMHC complexes able to be crosslinked by ultraviolet irradiation; even as monomers, these efficiently and specifically stained cognate T cells.

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    A chemical toolkit for proteins--an expanded genetic code

    Nature Review Mol Cell Biol
    Jianming Xie & Peter G. Schultz

    Recently, a method to encode unnatural amino acids with diverse physicochemical and biological properties genetically in bacteria, yeast and mammalian cells was developed. Over 30 unnatural amino acids have been co-translationally incorporated into proteins with high fidelity and efficiency using a unique codon and corresponding transfer-RNA:aminoacyl-tRNA-synthetase pair.

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    The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determination

    Nature Biotechnology
    Jianming Xie, Lei Wang, Ning Wu, Ansgar Brock, Glen Spraggon & Peter G Schultz

    A recently developed method makes it possible to genetically encode unnatural amino acids with diverse physical, chemical or biological properties in Escherichia coli and yeast. We now show that this technology can be used to efficiently and site-specifically incorporate p-iodo-L-phenylalanine (iodoPhe) into proteins in response to an amber TAG codon.

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  • Patents

    Orthogonal translation components for the in vivo incorporation of unnatural amino acids

    EP2383340B1

    2004 Inventor: Lital Alfonta, Peter Schultz, Huaqiang Zeng, Jianming Xie, Ning Wu, Jiangyun Wang, Meng-Lin Tsao, Daniel Summerer, Dan Groff, Alexander Deiters, Jonathan R. Chittuluru, Mohammad R. Seyedsayamdost, James Turner

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    Adding photoregulated amino acids to the genetic code

    US20090181858A1

    2004 Inventor: Alexander Deiters, Ning Wu, Peter G. Schultz, David King, T. Ashton Cropp, Mohua Bose, Dan Groff, Jianming Xie, Eric Brustad

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    Site specific incorporation of heavy atom-containing unnatural amino acids into proteins for structure determination

    US7399619B2

    2004 Inventor: Jianming Xie, Lei Wang, Ning Wu, Peter G. Schultz Translation systems and other compositions including orthogonal aminoacyl tRNA-synthetases that preferentially charge an orthogonal tRNA with an iodinated or brominated amino acid are provided. Nucleic acids encoding such synthetases are also described, as are methods and kits for producing proteins including heavy atom-containing amino acids, e.g., brominated or iodinated amino acids. Methods of determining the structure of a protein, e.g., a protein into which a heavy atom has been site-specifically incorporated through use of an orthogonal tRNA/aminoacyl tRNA-synthetase pair, are also described.

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