Zhiqiang Zhang

Zhiqiang Zhang, PhD

Associate Professor of Transplant Immunology in Surgery, Academic Institute
Associate Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Biography

Dr. Zhiqiang Zhang earned his Ph.D. in Life Science from the University of Dalian University of Technology, Dalian, China, in 1999. He held faculty appointments at the University of Texas, MD Anderson Cancer Center, Houston Texas, and the Baylor research Institute, Baylor Institute for Immunology Research, Dallas, Texas, and  adjunct faculty appointment at Baylor University, Waco, Texas, before becoming a member of Houston Methodist Research Institute in 2014. As a member of the Research Institute Transplant Immunology Research Program, he directs a research program focusing on inflammation and virus infection. 

Description of Research

Innate immunity plays a critical role in initiating immune response and pathogen clearance upon microbial infection. Using pattern recognition receptors, including intracellular receptors or cell surface receptors, immune cells sense and respond to pathogenic microbial infection. This triggers activation of various anti-pathogen signaling cascades leading to anti-microbial, type I interferon (IFN), and/or proinflammatory cytokine responses. Understanding the effect of various microbial infections on receptors and signaling pathways will provide molecular insights into the host defense machinery and potential therapeutic targets for treating microbial infection. In contrast, uncontrolled nucleic acid sensing, especially self-nucleic acid sensing, and excessive production of type 1 IFN and proinflammatory cytokines, have been implicated in the development of autoimmune diseases such as systemic lupus erythematosus (SLE). Knowing the self-nucleic acid sensing systems in immune cells will help us develop receptor antagonists as a new form of therapy for autoimmune diseases.

Studies conducted by Dr. Zhang ’s group indicate that many helicases are critical cytosolic sensors that recognize RNA, DNA, or c-di-GMP, triggering the IFN host immune response mediated by MAVS, TRIF, or STING. The anti-microbial pathogen activities of these helicases are regulated by protein ubiquitination. Further studies indicate that these helicases as well as the well-known IFI16, play little role in sensing neutrophil-derived mitochondrial DNA (mtDNA), which is the major inducer of IFN in SLE. Dr.
Zhang ’s group has:
i) Characterized DNA-binding proteins in monocyte. They expect to identify the cytosolic sensor to mtDNA.
ii) Screened all 70 members in the TRIM family and has found that at least 6 other TRIMs play important roles in regulating nucleic acid sensing.

Together, their studies will focus on revealing the unknown host defense mechanisms, autoimmune mechanisms, and ubiquitin-signaling pathways.

Areas Of Expertise

Autoimmune mechanisms Virus infection Type I interferon Proinflammatory cytokine response
Education & Training

Postdoctoral Fellowship, Chinese Academy of Sciences
MS, Dalian Univ of Technology
PhD, Dalian Univ of Technology
Postdoctoral Fellowship, The Pennsylvania State University
Postdoctoral Fellowship, Tufts University
Publications

Mechanisms involved in controlling RNA virus-induced intestinal inflammation
Zhang, E, Fang, M, Jones, C, Minze, LJ, Xing, J & Zhang, Z 2022, , Cellular and Molecular Life Sciences, vol. 79, no. 6, pp. 313. https://doi.org/10.1007/s00018-022-04332-z

The RNA helicase DHX15 is a critical regulator of natural killer-cell homeostasis and functions
Wang, G, Xiao, X, Wang, Y, Chu, X, Dou, Y, Minze, LJ, Ghobrial, RM, Zhang, Z & Li, XC 2022, , Cellular and Molecular Immunology, vol. 19, no. 6, pp. 687-701. https://doi.org/10.1038/s41423-022-00852-7

NF-?B signaling in inflammation and cancer
Zhang, T, Ma, C, Zhang, Z, Zhang, H & Hu, H 2021, , MedComm, vol. n/a, no. n/a. https://doi.org/10.1002/mco2.104

DHX15 is required to control RNA virus-induced intestinal inflammation
Xing, J, Zhou, X, Fang, M, Zhang, E, Minze, LJ & Zhang, Z 2021, , Cell Reports, vol. 35, no. 12, 109205, pp. 109205. https://doi.org/10.1016/j.celrep.2021.109205

Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells
Xing, J, Zhang, A, Du, Y, Fang, M, Minze, LJ, Liu, Y-J, Li, XC & Zhang, Z 2021, , Nature Communications, vol. 12, no. 1, 2681, pp. 2681. https://doi.org/10.1038/s41467-021-23003-4

The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-?B activation and the innate immune response
Zhang, Z 2020, , Cellular and Molecular Immunology. https://doi.org/10.1038/s41423-020-00564-w

The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-?B activation and the innate immune response
Gu, Z, Chen, X, Yang, W, Qi, Y, Yu, H, Wang, X, Gong, Y, Chen, Q, Zhong, B, Dai, L, Qi, S, Zhang, Z, Zhang, H & Hu, H 2020, , Cellular & Molecular Immunology. https://doi.org/10.1038/s41423-020-00564-w

Targeting NF-?B pathway for the therapy of diseases: mechanism and clinical study
Zhang, Z 2020, , Signal Transduction and Targeted Therapy, vol. 5, no. 1. https://doi.org/10.1038/s41392-020-00312-6

Targeting NF-?B pathway for the therapy of diseases: mechanism and clinical study
Yu, H, Lin, L, Zhang, Z, Zhang, H & Hu, H 2020, , Signal Transduction and Targeted Therapy, vol. 5, no. 1. https://doi.org/10.1038/s41392-020-00312-6

Plasmactoid dendritic cells express EphA2 to negatively regulate type I interferon production in response to viral infection
Zhang, Z 2020, , IMMUNOLOGY2020™, AAI Annual Meeting, 5/8/20. <https://www.jimmunol.org/content/204/1_Supplement/148.15/tab-article-info>

EphA2 phosphorylates NLRP3 and inhibits inflammasomes in airway epithelial cells
Zhang, A, Xing, J, Xia, T, Zhang, H, Fang, M, Li, S, Du, Y, Li, XC, Zhang, Z & Zeng, M-S 2020, , EMBO Reports, pp. e49666. https://doi.org/10.15252/embr.201949666

Identification of the E3 ligase TRIM29 as a critical checkpoint regulator of NK cell functions
Dou, Y, Xing, J, Kong, G, Wang, G, Lou, X, Xiao, X, Vivier, E, Li, XC & Zhang, Z 2019, , Journal of immunology (Baltimore, Md. : 1950), vol. 203, no. 4, pp. 873-880. https://doi.org/10.4049/jimmunol.1900171

Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
Lu, N, Li, Y, Zhang, Z, Xing, J, Sun, Y, Yao, S & Chen, L 2018, , Nature Communications, vol. 9, no. 1, 742. https://doi.org/10.1038/s41467-018-03128-9

TRIM29 negatively regulates the type I IFN production in response to RNA virus
Xing, J, Zhang, A, Minze, LJ, Li, XC & Zhang, Z 2018, , Journal of Immunology, vol. 201, no. 1, pp. 183-192. https://doi.org/10.4049/jimmunol.1701569

Erratum to: Ephrin receptor A2 is an epithelial cell receptor for Epstein–Barr virus entry (Nature Microbiology, (2018), 3, 2, (164-171), 10.1038/s41564-017-0080-8)
Zhang, H, Li, Y, Wang, HB, Zhang, A, Chen, ML, Fang, ZX, Dong, XD, Li, SB, Du, Y, Xiong, D, He, JY, Li, MZ, Liu, YM, Zhou, AJ, Zhong, Q, Zeng, YX, Kieff, E, Zhang, Z, Gewurz, BE, Zhao, B & Zeng, MS 2018, , Nature Microbiology, vol. 3, no. 9, pp. 1075. https://doi.org/10.1038/s41564-018-0155-1

Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry
Zhang, H, Li, Y, Wang, HB, Zhang, A, Chen, ML, Fang, ZX, Dong, XD, Li, SB, Du, Y, Xiong, D, He, JY, Li, MZ, Liu, YM, Zhou, AJ, Zhong, Q, Zeng, YX, Kieff, E, Zhang, Z, Gewurz, BE, Zhao, B & Zeng, MS 2018, , Nature Microbiology, vol. 3, no. 2, pp. 164-171. https://doi.org/10.1038/s41564-017-0080-8

Macrophage subpopulations and their impact on chronic allograft rejection versus graft acceptance in a mouse heart transplant model
Zhao, Y, Chen, S, Lan, P, Wu, C, Dou, Y, Xiao, X, Zhang, Z, Minze, L, He, X, Chen, W & Li, XC 2017, , American Journal of Transplantation. https://doi.org/10.1111/ajt.14543

TRIM29 promotes DNA virus infections by inhibiting innate immune response
Xing, J, Zhang, A, Zhang, H, Wang, J, Li, XC, Zeng, M-S & Zhang, Z 2017, , Nature Communications, vol. 8, no. 1, 945. https://doi.org/10.1038/s41467-017-00101-w

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract
Xing, J, Weng, L, Yuan, B, Wang, Z, Jia, L, Jin, R, Lu, H, Li, XC, Liu, Y-J & Zhang, Z 2016, , Nature immunology, vol. 17, no. 12, pp. 1373-1380. https://doi.org/10.1038/ni.3580

Corrigendum: Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract
Xing, J, Weng, L, Yuan, B, Wang, Z, Jia, L, Jin, R, Lu, H, Li, XC, Liu, Y-J & Zhang, Z 2016, , Nature immunology, vol. 17, no. 12, pp. 1479. https://doi.org/10.1038/ni1216-1479a