姓名：尹芝南
性别：
职称：教授，博士生导师，南开大学生命科学院院长
学科方向：1. 通过检测荧光蛋白标记的细胞因子，筛选影响初始T细胞分化和细胞因子分泌的小分子药物。我们将应用报告转基因小鼠(IFN-γGFP、IL-4GFP、IL-17GFP、IL-10GFP、Foxp-3GFP、IL-10RFP & Foxp-3RFP ) 中分离的初始T细胞，在体外诱导其向Th1、Th2、Th17以及Treg分化，然后在诱导分化过程中加入小分子化合物，进行高通量小分子药物筛选，鉴定出一批在初始T细胞分化过程中对其细胞因子分泌有特异性作用（上调或下调）的小分子，成为药物研发的先导化合物。
2．通过检测化学发光的荧光素酶报告基因(NF-kB-luc和TNF-α-luc)，筛选影响机体免疫反应的小分子药物。我们将培养免疫细胞，并在体外刺激免疫细胞的过程中对各种小分子化合物进行高通量筛选，通过检测NF-kB-luc和TNF-α-luc的表达水平，筛选小分子化合物对炎症和肿瘤的作用。
3．动物水平药物筛选平台。我们将应用已建立的肿瘤模型、关节炎模型和肠炎动物模型，对以上体外筛选的小分子化合物,通过活体动物成像技术在动物水平上进行进一步评估。
准备让学生参与的课题：
1.应用报告转基因小鼠的T细胞，进行高通量小分子药物筛选。
2. 中药活性成分（二氢黄酮甲醚）对免疫系统的调节机制。
3. 天然产物（DCB3503）及其衍生物对免疫应答的调节机制。
4. 不同的调节性T细胞亚群在自身免疫应答中的功能。
教师简介1984年毕业于湖北医科大学，1988年获得上海第二医科大学免疫学硕士学位。1992年底赴意大利国家肿瘤中心进修，从事肿瘤细胞转移扩散的免疫机制研究。两年之后，转至免疫学家Av. Mitchson所领导的德国风湿病中心（德国柏林自由大学），从事T细胞分化及功能及其在自身免疫性关节炎中的作用的机制研究，三年之后以优异的成绩（Sum Cum Laude）获得博士学位，其博士论文获得柏林自由大学“优秀论文奖”。1997年赴耶鲁大学医学院内科系风湿科从事博士后研究，1999年3月晋升为耶鲁大学医学院内科系风湿科助理研究员,2001年7月晋升为耶鲁大学医学院内科系风湿科助理教授，并于2006年7月晋升为副教授，同年获得耶鲁大学内科系科研成就奖。获得美国国立卫生研究院科研基金多项，近年来发表论文二十余篇，累积SCI影响因子为93.2，论文被引用次数已超过260次。于2007年3月起被聘任为南开大学生命科学院院长。随后被评为国家杰出青年基金获得者，并以首席科学家身份担任国家973项目计划，被评为教育部“长江学者”特聘教授。
代表性作品：
1. Tonutti, E., P. Sala, C. Feruglio, Z. Yin, and A. Colombatti. Phenotypic heterogeneity of persistent expansions of CD4+ CD8+ T cells. Clin Immunol Immunopathol 1994; 73:312-320.
2. Yin, Z., J. Braun, L. Neure, P. Wu, U. Eggens, A. Krause, T. Kamradt, and J. Sieper. T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines. Arthritis Rheum 1997; 40:69-79.
3. Yin, Z., J. Braun, L. Neure, P. Wu, L. Liu, U. Eggens, and J. Sieper. Crucial role of interleukin-10/interleukin-12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis. Arthritis Rheum 1997; 40:1788-1797.
4. Yin, Z., E. Gabriele, A. Leprini, R. Perris, and A. Colombatti. Differential cation regulation of the alpha 5 beta 1 integrin-mediated adhesion of leukemic cells to the central cell-binding domain of fibronectin. Cell Growth Differ 1997; 8:1339-1347.
5. Mertz, A.K., S. Ugrinovic, R. Lauster, P. Wu, M. Grolms, U. Bottcher, H. Appel, Z. Yin, E. Schiltz, S. Batsford, C. Schauer-Petrowski, J. Braun, A. Distler, and J. Sieper. Characterization of the synovial T cell response to various recombinant Yersinia antigens in Yersinia enterocolitica-triggered reactive arthritis. Heat-shock protein 60 drives a major immune response. Arthritis Rheum 1998; 4:315-326.
6. Yin, Z., E. Giacomello, E. Gabriele, L. Zardi, S. Aota, K.M. Yamada, B. Skerlavaji, R. Doliana, A. Colombatti, and R. Perris. Cooperative activity of alpha4beta1 and alpha4beta7 integrins in mediating human B-cell lymphoma adhesion and chemotaxis on fibronectin through recognition of multiple synergizing binding sites within the central cell-binding domain. Blood 1999; 93:1221-1230.
7. Yin, Z., S. Siegert, L. Neure, M. Grolms, L. Liu, U. Eggens, A. Radbruch, J. Braun, and J. Sieper. The elevated ratio of interferon gamma-/ interleukin-4-positive T cells found in synovial fluid and synovial membrane of rheumatoid arthritis patients can be changed by interleukin-4 but not by interleukin-10 or transforming growth factor beta. Rheumatology 1999; 38:1058-1067.
8. Yin, Z., D. Zhang, T. Welte, G. Bahtiyar, S. Jung, L. Liu, X. Fu, A. Ray, and J. Craft. Dominance of IL-12 over IL-4 in gdT cell differentiation leads to default production of IFN-g: dissociation between IL-12 signaling and GATA-3 expression. J Immunol 2000; 164: 3056-3064
9. Braun, J., Z. Yin, I. Spiller, S. Siegert, M.Rudwaleit, L. Liu, A. Radbruch, and J. Sieper. Low secretion of tumor necrosis factor a, but not other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis. Arthritis & Rheumatism 2000; 42:2039-2044
10. Rudwaleit, M., Z. Yin, S. Siegert, M. Grolms, A. Radbruch, J. Braun, and J. Sieper. Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4. Ann Rheum Dis 2000; 59:311-314
11. Rudwaleit, M., S. Siegert, Z. Yin, J. Eick, A. Thiel, A. Radbruch, J. Sieper, and J. Braun. Low T cell production of TNF-a and IFN-g in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-a gene polymorphism Ann Rheum Dis 2001; 60:36-42.
12. Spessotto, P., Z. Yin, G. Magro, R. Deutzmann, A. Chiu, A. Colombatti, and R. Perris. Laminin isoforms 8 and 10 are primary components of the subendothelial basement membrane promoting interaction with neoplastic lymphocytes. Cancer Res 2001; 61:339-347.
13. Yin, Z., C.Chen, S.J.Szabo, L.H.Glimcher, A.Ray, and J.Craft. T-bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-g by gd T cells. J Immunol 2002; 168:1566-1571.
14. Yin, Z., G.Bahtiyar, N.Zhang, L.Liu, M.P.Madaio, and J.Craft. IL-10 regulates murine lupus J Immunol 2002; 169:2148-2155.
15. Welte, T., A.M. Zhang, T. Wang, Z. Zhang, D. Hesslein, Z. Yin, A. Kano, Y. Iwamoto, E. Li, J.E. Craft, A.M. Bothwell, E. Fikrig, A.L. Bothwell, P.A. Foni, R.A. Flavell and X-Y Fu. Stat 3 deletion during hematopoiesis causes Crohn”s disease-like pathogenesis and lethality, revealing a critical role of stat3 in regulation of innate immunity. Proc Natl Acad Sci U S A 2003; 100:1879-1884
16. Gao, Y., W. Yang, M.Pang, E. Scully, M. Girardi, L.H. Augenlicht, J Craft and Z. Yin*. gd T cells provide early source of IFN-g in tumor immunity. J. Exp. Med 2003; 198: 433-442.
17. Wang, T., E. Scully, Z. Yin, J.H. Kim, S. Wang, J. Yang, M. Mamula, J.F. Anderson, J. Craft and E. Fikrig. IFN-g producing gdT cells help control murine West Nile virus infection. J Immunol 2003; 171:2524-2531.
18. Pan, M., I. Kang, J. Craft and Z. Yin*. Resistance to development of collagen-induced arthritis in C57BL/6 mice is due to a defect in secondary, but not in primary, immune response. J. Clin. Immunol 2004; 24: 481-491
19. Jiang, D., J. Liang, J. Hodge, B. Lu, Z. Zhu, S. Yu, J. Fan, Y. Gao, Z. Yin, R. Homer, C. Gerard, and P.W. Noble. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J. Clin. Invest 2004;14: 191-199
20. Gao, Y., J. Tao, M. O. Li, D. Zhang, H. Chi, O. Henegariu, S. Kaech, R. Davis, R. A. Flavell, and Z. Yin*. JNK1 is essential for CD8+ T cell-mediated tumor immune surveillance. J Immunol 2005; 175: 5783-5789
21. Gao, Y., D. Zhang, B. Sun, H Fujii, K.I. Kosuna, and Z. Yin*. Active Hexose Correlated Compound (AHCC) enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunol Immunother 2005, 16:1-9
22. You, X., M. Pang, W. Gao, H.S. Shiah, D. Zhang, F. Koumpouras, S. Wang, H. Zhou, J.A. Madri, D.C. Baker, Y.C. Cheng, and Z. Yin*. Effect of a novel tylophorine on inflammatory arthritis through inhibition of innate immune response. Arthritis & Rheumatism 2006;54:877-886
23. Wang, T., Y.Gao, E. Scully, D. Beasley, J. Anderson, Z. Yin, J. Craft, and E. Fikrig. gd T cells facilitate adaptive immunity against west nile virus infection in mice. J Immunol 2006, 177:1825-1832
24. Chen, L., W.He, S.T.Kim, J.Tao, Y. Gao, H.Chi, A.M.Intlekofer, B.Harvev, S.L.Reiner, Z.Yin*, R.A. Flavell, and J. Craft. Both epigenetic and transcriptional programs contribute to default IFN-g production by gd T cells. J Immunol . 2007 ;178(5):2730-2736
25. Tao, J., Y. Gao, M.O.Li, W. He, L. Chen, B.Harvev, R.J.Davis, R.A. Flavell, and Z. Yin*. JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response. Euro. J. Immunol 2007 ;37(3):818-829.
26. Lim JH, Stirling B, Derry J, Koga T, Jono H, Woo CH, Xu H, Bourne P, Ha UH, Ishinaga H, Xu H, Andalibi A, Feng XH, Zhu H, Huang Y, Zhang W, Weng X, Yan C, Yin Z, Briles DE, Davis RJ, Flavell RA, Li JD. Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. Immunity. 2007 27(2):349-360
27. Tong C, Yin Z, Song Z, Dockendorff A, Huang C, Mariadason J, Flavell RA, Davis RJ, Augenlicht LH, Yang W. c-Jun NH2-terminal kinase 1 plays a critical role in intestinal homeostasis and tumor suppression. Am J Pathol. 2007 171(1):297-303
28. Pedra JH, Tao J, Sutterwala FS, Sukumaran B, Berliner N, Bockenstedt LK, Flavell RA, Yin Z, Fikrig E. IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis. FEMS Immunol Med Microbiol. 2007 ;50(3):401-410.
Reviews
1. Muller, B., U. Gimsa, N.A. Mitchison, A. Radbruch, J. Sieper, and Z. Yin. Modulating the Th1/Th2 balance in inflammatory arthritis. Springer Semin Immunopathol 1998; 20:181-196.
2. Yin, Z., and J. Craft. gamma delta T cells in autoimmunity. Springer Semin Immunopathol 2000; 22:311-320.
电子邮件：yinzn@nankai.edu.cn
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