Dr Yongliang Zhang obtained his BSc in Biology from Zhejiang Normal University, China in 1992, his MS in Microbiology from Wuhan University, China in 1995, and his PhD in Molecular Microbiology in 2002 from the National University of Singapore (NUS), Singapore.
He performed his postdoctoral research in the Department of Immunology, University of Washington, USA, and the Department of Immunology, the University of Texas M. D. Anderson Cancer Center, USA. He was an Instructor in the Department of Immunology, M. D. Anderson Cancer Center before he joined the Department of Microbiology and the LSI Immunology Programme, NUS, as an Assistant Professor in 2009. He was promoted to Associate Professor with Tenure in 2017.
Dual-specificity phosphatases in health and disease
Phosphorylation and dephosphorylation is a major switch of cell signaling, playing fundamental roles in various aspects of cell life including proliferation, growth, function and cell death. Dual-specificity phosphatases (DUSPs), also known as MAPK phosphatases (MKPs), are a group of proteins which are able to dephosphorylate tyrosine and threonine/serine residues in their substrates including MAPKs, IRF3 and other important signaling molecules, thereby controlling the biological outcomes of signal events. Research in Dr Zhang’s laboratory focuses on deciphering the physiological and pathophysiological functions of various DUSPs in the following projects:
- DUSPs in immune response to microbial infection;
- DUSPs in inflammation and tumorigenesis;
- DUSPs in obesity and obesity-associated metabolic disorders.
In these projects, he and his colleagues use multiple animal models including chemical induced and genetic mutation caused cancer models (for colorectal cancer, B cell lymphoma, and lung cancer), obesity and obesity-associated disease models, and virus/bacterial infection models, as well as clinical sample analysis to address the function of these key molecules in cell signalling. Findings made by his group unveiled novel and important roles played by DUSPs/MKPs in diseases including infectious diseases, cancer and metabolic disorders. He has published research articles in top international journals including Nature, Nature Immunology, Immunity, EMBO J, PNAS, Oncogene and Cell Reports. The long term research goal is to target these proteins to develop novel therapies for human diseases including cancer, metabolic disease, and infection.
Project: Understanding the link between inflammation and cancer
Liu J., Li Y., Andiappan A., Yan Y., Tan K.S., Ong H. H., Kim T., Yu F., Zhang Y., Shi L., and Wang D.Y. 2018.Role of IL-13Ra2 in modulating IL-13 induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa. Allergy. (In press).
Cui C., Yang C., Song S., Fu S., Sun X., Yang L., He F., Zhang L., Zhang Y., and Deng Y. 2018. A novel two-component system modulates quorum sensing and pathogenicity in Burkholderia cenocepacia. Mol. Microbiol. (In press).
Cho S.S.L., Han J., James S.J., Png C.W., Weerasooriya M., Alonso S., and Zhang Y. 2017. Dual-specificity phosphatase 12 targets p38 MAP kinase to regulate macrophage response to intracellular bacterial infection. Front. Immunol. Oct 9; 8:1259. doi: 10.3389/fimmu.2017.01259.
Zhen, B., Shi, L., Guo, Y., Lv, Z., Tang, C., Niu, S., Tremblay, A., Venkataramani, M., Culpepper, C., Li, L., Zhou, Z., Mansour, A., Zhang, Y., Gewirtz, A., Kidder, K., Zen, K., and Liu, Y. 2016. Cd47-Sirpa interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells. PNAS. Sep 13; 113 (37): E5434-E5443. PMID: 27578867.
Chua, Y.L., Liong, K.H., Huang, C., Wong, H.S., Zhou, Q., Ler, S.S., Tang, Y., Low, C.P., Kuo, I., Zhang, Y., Wong, W., Lim, H.Y., Angeli, V., MacAry, P.A., Chua, K.Y., and Kemeny, D.M. 2016. Blomia tropicalis-Specific TCR Transgenic Th2 Cells Induce Inducible BALT and Severe Asthma in Mice by an IL-4/IL-13-Dependent Mechanism. J. Immunol. Nov 15; 197: 3771-3781. PMID: 27733553.
Ajjampur, S., Png, C.W., Chia, W.N., Zhang, Y., and Tan, K.S.W. 2016. Ex vivo and In vivo mice models to study Blastocystis spp. adhesion, colonization and pathology: Closer to proving Koch's Postulates. PLOS One. Aug. 10; 11(8): e0160458. PMID: 27508942.
Low, H., Png, C.W., Li, C., Wang, D., Wong, J.S.B., and Zhang, Y. 2016. Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness. Oncotarget. Aug. 25; 7:55473-55490. PMID: 27487154.
Low, H. and Zhang, Y. 2016 Regulatory roles of MAPK phosphatases in cancer. Immune Network. 16:85-98. PMID: 27162525.
Moorthy, A.N., Rai, P., Jiao, H., Wang, S., Tan, K.B., Qin, L., Watanabe, H., Zhang, Y., Narasaraju, T., and Chow, V.T. 2016. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget. April 12; 7:19372-19340. PMID: 27034012.
Png, C.W., Weerasooriya, M., Guo, J., James, S.J., Poh, H.M., Osato, M., Flavell, R.A., Dong, C., Yang, H., and Zhang, Y. 2016. DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis. Oncogene March; 35:206-17. PMID: 25772234.
Sheng, W., Png, C.W., Reynolds, J.M., and Zhang, Y. 2015. T cell-derived GM-CSF, regulation of expression and function. Immunome Research. 11:098 (1-6).
Png, C.W. and Zhang, Y. 2015. MAPK phosphatase 5 inhibits IRF3. Oncotarget. 6:19348-49. PMID: 26305722.
James, S.J., Jiao, H., The, H., Takahashi, H., Png, C.W., Phoon, M.C., Suzuki, Y., Sawasaki, T., Xiao, H., Chow, V.T.K., Yamamoto, N., Reynolds, J.M., Flavell, R.A., Dong, C., and Zhang, Y. 2015. MAPK phosphatase 5 expression induced by influenza and other RNA virus infection negatively regulates IRF3 activation and type I interferon response. Cell Reports. 10: 1722-1734. PMID: 25772359.
Zhang, Y., Nguyen, T., Tang, P., Kennedy, N.J., Jiao, H., Zhang, M., Reynolds, J.M., Jaeschke, A., Martin-Orozco, N., Chung, Y., He, W., Wang, C., Jia, W., Ge, B., Davis, R.J., Flavell, R.A., and Dong, C. 2015. Regulation of adipose tissue inflammation and insulin resistance by MAPK phosphatase 5. J. Biol. Chem. 290: 14875-14883. PMID: 25922079.
Jiao, H., Tang, T., and Zhang, Y. 2015. MAP kinase phosphatase 2 regulates macrophage-adipocyte interaction. PLOS One. 10: e0120755. PMID: 25816341.
Zhang, Y.*, Nallaparaju, K.C., Liu, X., Jiao, H., Reynolds, J.M., Wang, Z., and Dong, C.* 2015. MAPK phosphatase 7 regulates T cell differentiation via inhibiting ERK-mediated IL-2 expression. J. Immunol. 194: 3088-3095. (*Co-corresponding authors). PMID: 25716993.
Du, M., Liu, J.H., Chen, X., Xie, Y.D., Yuan, C.P., Xiang, Y., Sun, B., Lan, K., Chen, M.Z., James, S. J., Zhang, Y., Zhong, J., and Xiao, H. 2015. Casein Kinase II Controls TBK1/IRF3 Activation in Interferon Response against Viral Infection. J. Immunol. 194: 4477-4488. PMID: 25810395.
Sheng, W., Yang, F., Zhou, Y., Yang, H., Low, P.Y., Kemeny, D.M., Tan, P., Moh, A., Kaplan, M.H., Zhang, Y.*, and Fu, X.* 2014. STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation. Cell Research. 24: 1387-1402. (*Co-corresponding authors). PMID: 25412660.
Lim, M.X., Png, C.W., Tay, Y.B.C., Teo, D.W.J., Jiao, H., Tan, K.S.W., and Zhang, Y. 2014. Differential regulation of pro-inflammatory cytokine expression by mitogen-activated protein kinases in macrophages in response to intestinal parasite infection. Infect Immun. 82: 4789-4801. PMID: 25156742.
Negishi, H., Matsuki, K., Endo, N., Sarashina, H., Miki, S., Matsuda, A., Fukazawa, K., Taguchi-Atarashi, N., Ikushima, H., Yanai, H., Nishio, J., Honda, K., Fujioka, Y., Ohba, Y., Noda, T., Taniguchi, S., Nishida, E., Zhang, Y., Chi, H., Flavell, R.A., and Taniguchi, T. 2013. Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor-mediated enhancement of the MKP-IRF3 axis. PNAS. 111: 19884-19889. PMID: 24248350.
Chung, Y., Yamazaki, T., Kim, B., Zhang, Y., Reynolds, J.M., Martinez, G.J., Chang, S.H., Lim, H., Birkenbach, M., and Dong, C. 2013. Epstein Barr virus-induced 3 (EBI3) together with IL-12 negatively regulates T helper 17-mediated immunity to Listeria monocytogenes infection. PloS Pathog. 9: e1003628. PMID: 24068935.
Chung, Y., Lee, Y., Zhang, Y., Yamazaki, T., Zhou, D., Kang, C., and Dong, C. 2012. T cells and T cell tumors efficiently generate antigen-specific cytotoxic T cell immunity when modified with an NKT ligand. OncoImmunol. 1: 141-151. PMID: 22720235.
Wang, X., Zhang, F., Chen, F., Liu, D., Zheng, Y., Zhang, Y., Dong, C., and Su, B. 2011. MEKK3 regulates IFN-gamma production in T cells through the Rac1/2-dependent MAPK cascades. J. Immunol. 186: 5791-5800.
Nurieva, R.I., Zheng, S., Jin, W., Chung, Y., Zhang, Y., Martinez, G.J., Reynolds, J., Wang, S., Lin, X., Sun, S., Lozano, G., and Dong, C. 2010. The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation. Immunity. 32: 670-680.
Reynolds, J., Pappu, B.P., Peng, J., Martinez, G.J., Zhang, Y., Chung, Y., Ma, L., Yang, X.O., Nurieva, R.I., Tian, Q., and Dong, C. 2010. Toll-like receptor 2 signaling in CD4+ T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity. 32: 692-702.
Zhang, Y., Reynolds, J., Chang, S.H., Martin-Orozco, N., Chung, Y., Nurieva, R. and Dong, C. 2009. MKP-1 is necessary for T cell activation and function. J. Biol. Chem. 284: 30815-30824. PMID: 19748894.
Qian, F., Deng, J., Cheng, N., Welch, E.J., Zhang, Y., Malik, A.B., Flavell, R.A., Dong, C., and Ye, R.D. 2009. A non-redundant role for MKP5 in limiting ROS production and preventing LPS-induced vascular injury. EMBO J. 28: 2896-2907. PMID: 19696743.
Zhang, Y., and Dong, C. 2007. Regulatory mechanisms of mitogen-activated kinase signaling. (Review, correspondent author). Cellular and Molecular Life Sciences (CMLS) 64: 2771-2789.
Nurieva, R.I., Yang, X., Martinez, G., Zhang, Y., Panopoulos, A.D., Ma, L., Schluns, K., Tian, Q., Watowich, S., Jetten, A.M., and Dong, C. 2007. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 448: 480-483.
Hsu, M.Y., Zhang, Y., You, Y., Wang, D., Li, H., Duramad, O., Qin, X., Dong, C., and Lin, X. 2007. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nature Immunol. 8: 198-205.
Zhang, Y., Chung, Y., Bishop, C., Daugerty, B., Chute, H., Olst, P., Kurahara, C., Lott, F., Sun, N., Welcher, A., and Dong, C. 2006. Regulation of T cell activation and tolerance by PDL2. PNAS. 103: 11695-11700.
Nguyen, T., Liu, X.K., Zhang, Y., and Dong, C. 2006. BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation. J. Immunol. 176: 7354-7360.
Zhang, Y., and Dong, C. 2005. MAP kinases in immune responses. Cell. Mol. Immunol. 2:20-29.
Zhang, Y., Blattman, J.N., Kennedy, N.J., Duong, J., Nguyen, T., Wang, Y., Davis, R.J., Greenberg, P.D., Flavell, R.A., and Dong, C. 2004. Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature. 430:793-797. PMID: 15306813.
Yu, H.B., Zhang, Y.L., Lau, Y.L., Yao, F., Vilches, S., Merino, S., Tomas, J. M., Howard, S.P., and Leung, K.Y. 2005. Identification and characterization of putative virulence genes and gene clusters in Aeromonas hydrophila PPD134/91. Appl. Environ. Microbiol. 71: 4469-4477.
Zhang, Y.L., Lau, Y.L., Arakawa, E., and Leung, K.Y. 2003. Detection and genetic analysis of group II capsules in Aeromonas hydrophila. Microbiol. 149:1051-1060.
Zhang, Y.L., Arakawa, E., and Leung, K.Y. 2002. Novel Aeromonas hydrophila PPD134/91 genes involved in O-antigen and capsule biosynthesis. Infect. Immun. 70:2326-2335.
Zhang, Y.L., Ong, C.T., and Leung, K.Y. 2000. Molecular analysis of genetic differences between virulent and avirulent strains of Aeromonas hydrophila isolated from diseased fish. Microbiol. 146:999-1009.
Li, G.Q., Zhang, Y.L., and Xu, B.H. 1998. The ability of Bdellovibrio in the lysis of Vibrio fluvialis under various conditions. Acta Hydrobiologica Sinica. 22:265-270.
Zhang, Y.L., Yongliang Zhang 1, Julie Duong 1, Norman Kennedy 2, Roger J. Davis 2, Richard A. Flavell 3, and Chen Dong 1, Wei, Y.B., and Yang, Q.X. 1997. Isolation of an aerobic magnetotactic bacterium HM-1 and studies on its biological characteristics. J. Wuhan Uni. 43:775-780.
Zhang, Y.L., Yongliang Zhang 1, Julie Duong 1, Norman Kennedy 2, Roger J. Davis 2, Richard A. Flavell 3, and Chen Dong 1, Li, G. Q., and Xu, B.H. 1996. Identification of plaques formed by microbes in lakes and variation of Bdellovibrio bacteriovorus amount. Virol. Sinica. 11:99-102.