Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Jian Zhang, MD

Endowed Chair in Immunology Research
Professor of Pathology

Contact Information

Primary Office
1169 Medical Laboratories
25 S. Grand Avenue
Iowa City, IA 52242


MD, Hunan Medical University
MS, Hunan Medical University
Postdoctoral Fellow, Laboratoire d'Immunologie Hopital Marie Lannelongue
Postdoctoral Fellow, The John P. Robarts Research Institute

Research Summary

Dr. Jian Zhang studies molecular mechanisms of T cell activation and differentiation, and innate immune responses regulated by E3 ubiquitin ligases Cbl-b and Nedd4. His group has identified novel proteins regulated by Cbl-b in T cells and innate immune cells, and is investigating 1) how Cbl-b regulates T follicular helper cell development in systemic lupus erythematosus; and 2) how Cbl-b regulates the innate immune cells sensing Candida albicans infection. In addition, his group has also identified some novel substrates of Nedd4 in T cells, is studying Nedd4 in T helper cell development and autoimmunity. Further understanding of these E3 ubiquitin ligases in innate and adaptive immunity will lead to the development of therapeutic invention for human diseases such as rheumatoid arthritis, multiple sclerosis, allergic asthma, and infectious diseases.


Tang, J., Tu, S., Lin, G., Guo, H., Yan, C., Liu, Q., Huang, L., Tang, N., Xiao, Y., Pope, R. M., Rajaram MVS,, Amer, A. O., Ahmer, B. M., Gunn, J. S., Wozniak, D. J., Tao, L., Coppola, V., Zhang, L., Langdon, W. Y., Torrelles, J. B., Lipkowitz, S. & Zhang, J. (2020). Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia. The Journal of experimental medicine, 217(4). PMID: 31999304.

Kim, V. Y., Batty, A., Li, J., Kirk, S. G., Crowell, S. A., Jin, Y., Tang, J., Zhang, J., Rogers, L. K., Deng, H. X., Nelin, L. D. & Liu, Y. (2019). Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic Candida albicans Infection in Mice. Journal of immunology (Baltimore, Md. : 1950), 203(8), 2239-2251. PMID: 31501257.

Tang, N., Yang, L., Li, D., Liu, R. & Zhang, J. (2019). Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination. Biochemistry and Biophysics Reports, 18. PMID: 31061898.

Tang, R., Langdon, W. Y. & Zhang, J. (2019). Regulation of immune responses by E3 ubiquitin ligase Cbl-b. Cell. Immunol., 340, 103878. PMID: 30442330.

Ouyang, S., Zeng, Q., Tang, N., Guo, H., Tang, R., Yin, W., Wang, A., Tang, H., Zhou, J., Xie, H., Langdon, W. Y., Yang, H. & Zhang, J. (2019). Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells. Journal of immunology (Baltimore, Md. : 1950), 202(5), 1441-1452. PMID: 30692211.

Tang, R., Langdon, W. Y. & Zhang, J. (2018). Regulation of immune responses by E3 ubiquitin ligase Cbl-b. Cellular immunology. PMID: 30442330.

Tang, J., Lin, G., Langdon, W. Y., Tang, L. & Zhang, J. (2018). Regulation of C-type lectin receptor-mediated anti-fungal immunity. Front Immunol, 9, 123. PMID: 29449845.

Tang, J., Zhang, J. (2018). CBLB. In Encyclopedia of Signaling Molecules, 2nd Edition. Springer.

Tang, J. (In Press). Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity. Frontiers, 9. DOI: doi: 10.3389/fimmu.2018.00123.

Arcos, J., Sidiki, S., Guo, H., Sasindran, S. J., Scordo, J. M., Moliva, J. J., Diangelo, J. I., Zhang, J., Turner, J. & Torrelles, J. B. (2017). Mycobacterium tuberculosis cell wall released fragments by the action of the human lung mucosa modulate macrophages to control the infection in an IL-10 dependent manner. (Vols. 10). (5), pp. 1248-1258. Mucosal Immunol. PMID: 28000679.

Yin, J., Zhang, J. & Liu, Q. (2017). The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases. Clin Immunol, 180, 5-10. PMID: 28365317.

Nuro-Gyina, P. K., Rieser, E. L., Granitto, M. C., Pei, W., Liu, Y., Lee, P. W., Aqel, S., Zhang, J., Lovett-Racke, A. E., Racke, M. K. & Yang, Y. (2016). Regulation of effector function of CNS autoreactive CD4 T cells through inhibitory receptors and IL-7Ra. Journal of Neuroinflammation, 13(1), 302. PMID: 27912762.

Song, C., He, L., Zhang, J., Ma, H., Yuan, X., Hu, G., Tao, L., Zhang, J. & Meng, J. (2016). Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL-1ß/IL-1R1/MyD88/NF-?B pathway. Journal of Cellular and Molecular Medicine, 20(11), 2064-2077. PMID: 27306439.

Yang, L., Qiao, G., Hassan, Y., Li, Z., Zhang, X., Kong, H., Zeng, W., Yin, F. & Zhang, J. (2016). Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response. Archivum Immunologiae et Therapiae Experimentalis, 64(5), 417-23. PMID: 27197661.

Xiao, Y., Liu, J., Peng, Y., Xiong, X., Huang, L., Yang, H., Zhang, J. & Tao, L. (2016). GSTA3 attenuates renal interstitial fibrosis by inhibiting TGF-b-induced tubular epithelial-mesenchymal transition and fibronectin expression. G. Camussi (Eds.) (Vols. 11). pp. e0160855. PLoS One. PMID: 27602565.

Xiao, Y., Tang, J., Guo, H., Zhao, Y., Tang, R., Ouyang, S., Zeng, Q., Rappleye, C. A., Rajaram, M. V., Schlesinger, L. S., Tao, L., Brown, G. D., Langdon, W. Y., Li, B. T. & Zhang, J. (2016). Targeting CBLB as a potential therapeutic approach for disseminated candidiasis. Nature Medicine, 22(8), 906-14. PMID: 27428899.

Xiao, Y., Qiao, G., Tang, J., Tang, R., Guo, H., Warwar, S., Langdon, W. Y., Tao, L. & Zhang, J. (2015). Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation. Journal of Immunology, 195(9), 4218-4227. PMID: 26416283.

Qiao, G., Yang, L., Li, Z., Williams, J. W. & Zhang, J. (2015). A77 1726, the active metabolite of leflunomide, attenuates lupus nephritis by promoting the development of regulatory T cells and inhibiting IL-17-producing double negative T cells. Clinical Immunology, 157(2), 166-174. PMID: 25638413.

Zhao, Y., Guo, H., Qiao, G., Zucker, M., Langdon, W. Y. & Zhang, J. (2015). E3 Ubiquitin Ligase Cbl-b Regulates Thymic-Derived CD4+CD25+ Regulatory T Cell Development by Targeting Foxp3 for Ubiquitination. Journal of Immunology, 194(4), 1639-1645. PMID: 25560411.

Zhao, Y., Lei, M., Wang, Z., Qiao, G., Yang, T. & Zhang, J. (2014). TCR-induced, PKC-?-mediated NF-?B activation is regulated by a caspase-8-caspase-9-caspase-3 cascade. Biochemical and Biophysical Research Communications, 450(1), 526-31. PMID: 24924627.

Zhang, J., Liu, Q. & Langdon, W. T. (2014). Cbl-b: Roles in T Cell Tolerance, Proallergic T Cell Development, and Cancer Immunity (Invited Review). Inflammation and Cell Signaling, 1, 105. PMID: 26082933.

Veselits, M., Tanaka, A., Lipkowitz, S., O'Neill, S., Sciammas, R., Finnegan, A., Zhang, J. & Clark, M. R. (2014). Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes. PloS One, 9(3), e89792. PMID: 24651487.

Qiao, G., Ying, H., Zhao, Y., Liang, Y., Guo, H., Shen, H., Li, Z., Solway, J., Tao, E., Chiang, Y. J., Lipkowitz, S., Penninger, J. M., Langdon, W. Y. & Zhang, J. (2014). E3 ubiquitin ligase Cbl-b suppresses proallergic T cell development and allergic airway inflammation. Cell Reports, 6(4), 709-23. PMID: 24508458.

Zhang, B., Adesanya, T. M., Zhang, L., Xie, N., Chen, Z., Fu, M., Zhang, J., Tan, T., Kilic, A., Li, Z., Zhu, H. & Xie, X. (2014). Delivery of placenta-derived mesenchymal stem cells ameliorates ischemia induced limb injury by immunomodulation. Cellular Physiology and Biochemistry : international Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 34(6), 1998-2006. PMID: 25562148.

Qiao, G., Zhao, Y., Li, Z., Tang, P. Q., Langdon, W. Y., Yang, T. & Zhang, J. (2013). T cell activation threshold regulated by E3 ubiquitin ligase Cbl-b determines fate of inducible regulatory T cells. Journal of Immunology, 191(2), 632-639. PMID: 23749633.

Guo, H., Qiao, G., Ying, H., Li, Z., Zhao, Y., Liang, Y., Yang, L., Lipkowitz, S., Penninger, J. M., Langdon, W. Y. & Zhang, J. (2012). E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell Reports, 1(5), 472-82. PMID: 22763434.

Qiao, G., Yang, L., Li, Z., Ying, H., Hassen, Y., Yin, F. & Zhang, J. (2012). Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism. Clinical Immunology, 143(2), 128-133. PMID: 22459706.

Ying, H., Li, Z., Yang, L. & Zhang, J. (2011). Syk mediates BCR- and CD40-signaling integration during B cell activation. Immunobiology, 216(5), 566-70. PMID: 21074890.

Yang, L., Qiao, G., Ying, H., Zhang, J. & Yin, F. (2010). TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha. Biochemical and Biophysical Research Communications, 400(1), 16-20. PMID: 20691662.

Ying, H., Yang, L., Qiao, G., Li, Z., Zhang, L., Yin, F., Xie, D. & Zhang, J. (2010). Cutting edge: CTLA-4--B7 interaction suppresses Th17 cell differentiation. Journal of Immunology, 185(3), 1375-8. PMID: 20601598.

Qiao, G., Li, Z., Minto, A. W., Shia, J., Yang, L., Bao, L., Tschopp, J., Gao, J. X., Wang, J., Quigg, R. J. & Zhang, J. (2010). Altered thymic selection by overexpressing cellular FLICE inhibitory protein in T cells causes lupus-like syndrome in a BALB/c but not C57BL/6 strain. Cell Death and Differentiation, 17(3), 522-33. PMID: 19816511.

Bao, L., Haas, M., Pippin, J., Wang, Y., Miwa, T., Chang, A., Minto, A. W., Petkova, M., Qiao, G., Song, W. C., Alpers, C. E., Zhang, J., Shankland, S. J. & Quigg, R. J. (2009). Focal and segmental glomerulosclerosis induced in mice lacking decay-accelerating factor in T cells. The Journal of Clinical Investigation, 119(5), 1264-74. PMID: 19349693.

Qiao, G., Li, Z., Molinero, L., Alegre, M. L., Ying, H., Sun, Z., Penninger, J. M. & Zhang, J. (2008). T-cell receptor-induced NF-kappaB activation is negatively regulated by E3 ubiquitin ligase Cbl-b. Molecular and Cellular Biology, 28(7), 2470-80. PMID: 18227156.

Qiao, G., Lei, M., Li, Z., Sun, Y., Minto, A., Fu, Y. X., Ying, H., Quigg, R. J. & Zhang, J. (2007). Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B. Journal of Immunology, 179(7), 4473-9. PMID: 17878343.

Chang, X., Chen, L., Wen, J., Godfrey, V. L., Qiao, G., Hussien, Y., Zhang, J. & Gao, J. X. (2006). Foxp3 controls autoreactive T cell activation through transcriptional regulation of early growth response genes and E3 ubiquitin ligase genes, independently of thymic selection. Clinical Immunology, 121(3), 274-85. PMID: 16945588.

Li, D., Gál, I., Vermes, C., Alegre, M. L., Chong, A. S., Chen, L., Shao, Q., Adarichev, V., Xu, X., Koreny, T., Mikecz, K., Finnegan, A., Glant, T. T. & Zhang, J. (2004). Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. Journal of Immunology, 173(12), 7135-9. PMID: 15585834.

Zheng, X., Gao, J. X., Chang, X., Wang, Y., Liu, Y., Wen, J., Zhang, H., Zhang, J., Liu, Y. & Zheng, P. (2004). B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus. Journal of Immunology, 173(4), 2253-61. PMID: 15294937.

Glant, T. T., Adarichev, V. A., Nesterovitch, A. B., Szanto, S., Oswald, J. P., Jacobs, J. J., Firneisz, G., Zhang, J., Finnegan, A. & Mikecz, K. (2004). Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis. The American Journal of the Medical Sciences, 327(4), 188-95. PMID: 15084914.

Arreaza, G., Salojin, K., Yang, W., Zhang, J., Gill, B., Mi, Q. S., Gao, J. X., Meagher, C., Cameron, M. & Delovitch, T. L. (2003). Deficient activation and resistance to activation-induced apoptosis of CD8+ T cells is associated with defective peripheral tolerance in nonobese diabetic mice. Clinical Immunology, 107(2), 103-15. PMID: 12763479.

Zhang, J., Bárdos, T., Shao, Q., Tschopp, J., Mikecz, K., Glant, T. T. & Finnegan, A. (2003). IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism. Journal of Immunology, 170(7), 3495-503. PMID: 12646610.

Finnegan, A., Kaplan, C. D., Cao, Y., Eibel, H., Glant, T. T. & Zhang, J. (2003). Collagen-induced arthritis is exacerbated in IL-10-deficient mice. Arthritis Research & Therapy, 5(1), R18-24. PMID: 12716449.

Bardos, T., Czipri, M., Vermes, C., Finnegan, A., Mikecz, K. & Zhang, J. (2003). CD4+CD25+ immunoregulatory T cells may not be involved in controlling autoimmune arthritis. Arthritis Research & Therapy, 5(2), R106-13. PMID: 12718754.

Finnegan, A., Grusby, M. J., Kaplan, C. D., O'Neill, S. K., Eibel, H., Koreny, T., Czipri, M., Mikecz, K. & Zhang, J. (2002). IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent mechanisms. Journal of Immunology, 169(6), 3345-52. PMID: 12218156.

Bárdos, T., Zhang, J., Mikecz, K., David, C. S. & Glant, T. T. (2002). Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age. Arthritis and Rheumatism, 46(9), 2465-75. PMID: 12355495.

Zhang, J., Bárdos, T., Li, D., Gál, I., Vermes, C., Xu, J., Mikecz, K., Finnegan, A., Lipkowitz, S. & Glant, T. T. (2002). Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. Journal of Immunology, 169(5), 2236-40. PMID: 12193687.

Bárdos, T., Czipri, M., Vermes, C., Zhang, J., Mikecz, K. & Glant, T. T. (2002). Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice. Clinical and Experimental Immunology, 129(2), 224-31. PMID: 12165077.

Bárdos, T., Mikecz, K., Finnegan, A., Zhang, J. & Glant, T. T. (2002). T and B cell recovery in arthritis adoptively transferred to SCID mice: antigen-specific activation is required for restoration of autopathogenic CD4+ Th1 cells in a syngeneic system. Journal of Immunology, 168(12), 6013-21. PMID: 12055209.

Vermes, C., Jacobs, J. J., Zhang, J., Firneisz, G., Roebuck, K. A. & Glant, T. T. (2002). Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts. The Journal of Biological Chemistry, 277(19), 16879-87. PMID: 11884403.

Zhang, J., Bárdos, T., Mikecz, K., Finnegan, A. & Glant, T. T. (2001). Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis. Journal of Immunology, 166(8), 4981-6. PMID: 11290777.

Zhang, J., Salojin, K. V. & Delovitch, T. L. (2001). CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription. International Immunology, 13(3), 377-84. PMID: 11222507.

Glant, T. T., Bárdos, T., Vermes, C., Chandrasekaran, R., Valdéz, J. C., Otto, J. M., Gerard, D., Velins, S., Lovász, G., Zhang, J., Mikecz, K. & Finnegan, A. (2001). Variations in susceptibility to proteoglycan-induced arthritis and spondylitis among C3H substrains of mice: evidence of genetically acquired resistance to autoimmune disease. Arthritis and Rheumatism, 44(3), 682-92. PMID: 11263784.

Zhang, J., Mikecz, K., Finnegan, A. & Glant, T. T. (2000). Spontaneous thymocyte apoptosis is regulated by a mitochondrion-mediated signaling pathway. Journal of immunology, 165(6), 2970-4. PMID: 10975804.

Gao, J. X., Zhang, J., Awaraji, C., Bhatia, M., Jevnikar, A., Singh, B., Bell, D. & Delovitch, T. L. (2000). Preferential proliferation and differentiation of double-positive thymocytes into CD8(+) single-positive thymocytes in a novel cell culture medium. Cellular immunology, 202(1), 41-53. PMID: 10873305.

Zhang, J., Gao, J. X., Salojin, K., Shao, Q., Grattan, M., Meagher, C., Laird, D. W. & Delovitch, T. L. (2000). Regulation of fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase. The Journal of Experimental Medicine, 191(6), 1017-30. PMID: 10727463.

Salojin, K. V., Zhang, J., Meagher, C. & Delovitch, T. L. (2000). ZAP-70 is essential for the T cell antigen receptor-induced plasma membrane targeting of SOS and Vav in T cells. The Journal of Biological Chemistry, 275(8), 5966-75. PMID: 10681590.

Salojin, K. V., Zhang, J. & Delovitch, T. L. (1999). TCR and CD28 are coupled via ZAP-70 to the activation of the Vav/Rac-1-/PAK-1/p38 MAPK signaling pathway. Journal of immunology, 163(2), 844-53. PMID: 10395678.

Zhang, J., Salojin, K. V., Gao, J. X., Cameron, M. J., Bergerot, I. & Delovitch, T. L. (1999). p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. Journal of immunology, 162(7), 3819-29. PMID: 10201899.

Zhang, J., Salojin, K., Gao, J. X., Cameron, M., Geisler, C. & Delovitch, T. L. (1998). TCR alpha beta chains associate with the plasma membrane independently of CD3 and TCR zeta chains in murine primary T cells. Journal of immunology, 161(6), 2930-7. PMID: 9743355.

Zhang, J., Salojin, K. & Delovitch, T. L. (1998). Sequestration of CD4-associated LcK from the TCR complex may elicit T cell hyporesponsiveness in nonobese diabetic mice. Journal of Immunology, 160(3), 1148-1157.

Salojin, K., Zhang, J., Madrenas, J. & Delovitch, T. L. (1998). T cell anergy and impaired T cell relceptor signaling: possible relationship to the development of autoimmune disease. (Vols. 19). pp. 467. Immunol Today.

Arreaza, G. A., Bergerot, B., Cameron, M. J., Salojin, K., Zhang, J., Tung, H. & Delovitch, T. L. (1998). Immune dysregulation elicits type 1 diabetes mellitus in NOD mice. Can J Diabet Care, 22(S3), 20.

Zhang, J., Zhou, W. B., Wang, H. L. & Guo, S. S. (1997). The effects of T cell subpopulations and recombinant interleukin (IL)-2 on peripheral B cell function in patients with myasthenia gravis. Human Antibodies, 8(2), 90-94.

Salojin, K., Zhang, J., Cameron, M., Gill, B., Arreaza, G., Ochi, A. & Delovitch, T. L. (1997). Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice. The Journal of experimental medicine, 186(6), 887-97. PMID: 9294143.

Zhang, J., Cohen-Kaminsky, S. & Berrih-Aknin, S. (1995). Macrophage subpopulations in the thymic hyperplasia of patients with Myasthenia Gravis. Human Antibodies, 6(4), 153-160. DOI: 10.3233/HAB-1995-6405.