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Zhiqiang Zhang, PhD

Assistant Professor of Transplant Immunology in Surgery, Institute for Academic Medicine
Assistant 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 Proinflammatory cytokine response Type I interferon
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

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. DOI: 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. DOI: 10.4049/jimmunol.1701569

Author Correction: 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. DOI: 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, pp. 1-8. DOI: 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. DOI: 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. DOI: 10.1038/s41467-017-00101-w

TRIM29 promotes persistence of oncogenic DNA viruses by inhibiting innate immune response
Zhang, Z 2017, IMMUNOLOGY 2017™ AAI Annual Meeting, Washington DC, United States, 5/12/17 - 5/16/17, .

RNA Virus hijacks TRIM29 to suppress the host innate immune response
Zhang, Z 2017, IMMUNOLOGY 2017™ AAI Annual Meeting, Washington DC, United States, 5/12/17 - 5/16/17, .

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. DOI: 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. DOI: 10.1038/ni1216-1479a

NFATC3 promotes IRF7 transcriptional activity in plasmacy--toid dendritic cells
Bao, M, Wang, Y, Liu, Y, Shi, P, Lu, H, Sha, W, Weng, L, Hanabuchi, S, Qin, J, Plumas, J, Chaperot, L, Zhang, Z & Liu, Y-J 2016, The Journal of experimental medicine, vol. 213, no. 11, pp. 2383-2398. DOI: 10.1084/jem.20160438

Rpl22 Loss Selectively Impairs aß T Cell Development by Dysregulating Endoplasmic Reticulum Stress Signaling
Solanki, NR, Stadanlick, JE, Zhang, Y, Duc, A-C, Lee, S-Y, Lauritsen, JPH, Zhang, Z & Wiest, DL 2016, Journal of Immunology, vol. 197, no. 6, pp. 2280-9. DOI: 10.4049/jimmunol.1600815

Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response
Xia, X, Mai, J, Xu, R, Perez, JET, Guevara, ML, Shen, Q, Mu, C, Tung, HY, Corry, DB, Evans, SE, Liu, X, Ferrari, M, Zhang, Z, Li, XC, Wang, RF & Shen, H 2015, Cell Reports, vol. 11, no. 6, pp. 957-966. DOI: 10.1016/j.celrep.2015.04.009

Human NLRP3 Inflammasome senses multiple types of bacterial RNAs
Sha, W, Mitoma, H, Hanabuchi, S, Bao, M, Weng, L, Sugimoto, N, Liu, Y, Zhang, Z, Zhong, J, Sun, B & Liu, YJ 2014, Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 45, pp. 16059-16064. DOI: 10.1073/pnas.1412487111

DHX15 senses double-stranded RNA in myeloid dendritic cells
Lu, H, Lu, N, Weng, L, Yuan, B, Liu, YJ & Zhang, Z 2014, Journal of Immunology, vol. 193, no. 3, pp. 1364-1372. DOI: 10.4049/jimmunol.1303322

The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells
Liu, Y, Lu, N, Yuan, B, Weng, L, Wang, F, Liu, YJ & Zhang, Z 2014, Cellular and Molecular Immunology, vol. 11, no. 1, pp. 49-57. DOI: 10.1038/cmi.2013.40

The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-Induced NLRP3 inflammasome activation
Weng, L, Mitoma, H, Tricot, C, Bao, M, Liu, Y, Zhang, Z & Liu, YJ 2014, Journal of Immunology, vol. 193, no. 7, pp. 3676-3682. DOI: 10.4049/jimmunol.1401448

The DHX33 RNA Helicase Senses Cytosolic RNA and Activates the NLRP3 Inflammasome
Mitoma, H, Hanabuchi, S, Kim, T, Bao, M, Zhang, Z, Sugimoto, N & Liu, YJ 2013, Immunity, vol. 39, no. 1, pp. 123-135. DOI: 10.1016/j.immuni.2013.07.001

The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA
Zhang, Z, Bao, M, Lu, N, Weng, L, Yuan, B & Liu, YJ 2013, Nature Immunology, vol. 14, no. 2, pp. 172-178. DOI: 10.1038/ni.2492

The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type i interferon immune response
Parvatiyar, K, Zhang, Z, Teles, RM, Ouyang, S, Jiang, Y, Iyer, SS, Zaver, SA, Schenk, M, Zeng, S, Zhong, W, Liu, ZJ, Modlin, RL, Liu, YJ & Cheng, G 2012, Nature Immunology, vol. 13, no. 12, pp. 1155-1161. DOI: 10.1038/ni.2460