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免疫学博导 王四清

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王四清 教授

   

学习工作经历:

1989-1994 白求恩医科大学           预防医学            学士

1997-2000 中国预防医学科学院       病原生物学          硕士

2000-2003 美国康涅狄格州立大学健康中心                 博士后                           

2003-2004 美国阿肯色州立大学医学院                     博士后

2004-2006 美国得克萨斯州立大学MD安德森癌症中心       博士后

2006-2007美国佛罗里达州立大学医学院              Research Associate                           

2007-2008美国阿肯色州立大学医学院                Research Associate

2008-2010美国犹他州立大学医学院                  Research Associate

2012-至今吉林大学第一医院肿瘤免疫室                     教授         

               

个人简介:

在Cancer Cell,Nat Commun,Blood,Leukeima和PNAS等期刊发表论文26篇,累积影响因子250分。另外发表国际学术会议摘要20余篇。主持国家自然科学基金面上项目1项。以主要参与人的身份曾参与美国 NIH及其他基金会科研项目10余项。

主要研究领域如下:

1.        Dectin-1 活化的DCs 通过诱导Th9发挥强有力抗肿瘤效应: Th9细胞为新型强有力抗肿瘤效应细胞。我们研究发现dectin-1 活化的DCs诱导很强的 Th9 反应,而且以dectin-1 活化的DCs为基础的疫苗体内诱导很强的抗肿瘤效应。此项研究为dectin-1 活化的DCs临床治疗肿瘤提供了重要依据。

2.        Th9/Tc9的诱导及其在肿瘤免疫治疗中的应用:肿瘤特异性Th9/Tc9是最近发现的具有很强抗肿瘤活性的效应T细胞亚型,我们主要研究如何在体内外更有效地诱导Th9/Tc9细胞用于临床肿瘤治疗。

3.        肿瘤微环境: 我们在国际上最早发现巨噬细胞(Mφs),尤其是肿瘤相关Mφs,对骨髓瘤细胞提供保护, 并导致肿瘤耐药性的产生。此项研究为以Mφs 为靶点的肿瘤临床治疗方案提供了理论依据。

4.        阐明肿瘤来源的树突状细胞 (DC) 的生物学特性: 我们在国际上首次发现,肿瘤通过活化 p38 MAP 激酶抑制 DC 分化。在DC分化过程中加入p38 抑制剂能有效扭转肿瘤对 DC 分化的抑制作用, 并恢复 DC 的表型和功能。这一研究揭示了肿瘤免疫缺陷新机制,为设计更有效的 DC 肿瘤疫苗提供了新思路。

 

专业:细胞生物学/免疫学

 

主要研究方向:

1. 肿瘤免疫;

2. 肿瘤微环境;

3. 血液肿瘤遗传学和分子生物学方面的研究。

 

代表性论文:

1.        Yuxue Jiang, Jintong Chen, Enguang Bi, Yinghua Zhao, Tianxue Qin, Yiming Wang, Alison Wang, Sujun Gao, Qing Yi, Siqing Wang#. TNF-α enhances Th9 cell differentiation and antitumor immunity via TNFR2-dependent pathways. Journal for ImmunoTherapy of Cancer. 2018 (in press). IF: 8.374

2.        Ning Liu, Yuxue Jiang, Jintong Chen, He Nan, Yinghua Zhao, Xiao Chu, Alison Wang, Dongjiao Wang, Tianxue Qin, Sujun Gao, Qing Yi, Ying Yue#, Siqing Wang#. IL-33 drives the antitumor effects of dendritic cells via the induction of Tc9 cells. Cell Mol Immunol. 2018 (in press). IF: 7.551

3.        Chen J, Zhao Y, Jiang Y, Gao S, Wang Y, Wang D, Wang A, Yi H, Gu R, Yi Q, Wang S#. Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells. Front Immunol. 2018 Jul 31;9:1787. doi: 10.3389/fimmu.2018.01787. eCollection 2018. IF:5.11

4.        Wang D, Gao S, Chen J, Zhao Y, Jiang Y, Chu X, Wang X, Liu N, Qin T, Yi Q, Yue Y#, Wang S#. Dectin-1 stimulates IL-33 expression in dendritic cells via upregulation of IRF4. Lab Invest. 2018 Jun;98(6):708-714. doi: 10.1038/s41374-018-0047-2. IF: 4.254

5.        Bi E, Ma X, Lu Y, Yang M, Wang Q, Xue G, Qian J, Wang S, Yi Q. Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7. Sci Signal. 2017 Oct 10;10(500).

6.        Wang Q, Lu Y, Li R, Jiang Y, Zheng Y, Qian J, Bi E, Zheng C, Hou J, Wang S# and Yi Q#. Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia. 2017 June; doi:10.1038/leu.2017.193. IF: 11.702

7.        Xiaoqing Zhu*, Yinghua Zhao*, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao, Siqing Wang. Dectin-1 signaling inhibits osteoclastogenesis via IL-33-induced inhibition of NFATc1. Oncotarget. 2017; 8:53366-53374.

8.        Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M. Hermann, Thorsten R. Doeppner, Fengyan Jin, Yun Dai, Jiang Wu. Identification of the histone lysine demethylase KDM4A/JMJD2A as a novel epigenetic target in M1 macrophage polarization induced by oxidized LDL. Oncotarget. 2017; doi.org/10.18632/oncotarget.17748

9.        Chen J, Zhao Y, Chu X, Lu Y , Wang S#, Yi Q#. Dectin-1-activated dendritic cells: A potent Th9 cell inducer for tumor immunotherapy. Oncoimmunology. 2016 Sep 27;5(11):e1238558. IF: 7.719

10.     Zhao Y, Chu X, Chen J, Wang Y, Gao S, Jiang Y, Zhu X, Tan G, Zhao W, Yi H, Xu H, Ma X, Lu Y#, Yi Q#, Wang S#. Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells. Nat Commun. 2016 Aug 5;7:12368. IF: 12.124

11.     Lu Y, Zhang M, Wang S, Hong B, Wang Z, Li H, Zheng Y, Yang J, Davis R, Qian J, Hou J, and Yi Q. p38 MAPK-inhibited dendritic cells induce superior antitumor immune responses and overcome regulatory T cell-mediated immunosuppression. Nat Commun. 2014 Jun 24;5:4229. IF: 12.124

12.     Lu Y, Hong B, Li H, Zheng Y, Zhang M, Wang S, Qian J, Yi Q. Tumor-specific IL-9-producing CD8+ Tc9 cells are superior effector than type-I cytotoxic Tc1 cells for adoptive immunotherapy of cancers. Proc Natl Acad Sci U S A. 2014 Jan 27.

13.     Henderson JW, Wang S, Egger MJ, Masters M, Nygaard I. Can women correctly contract their pelvic floor muscles without formal instruction? Female Pelvic Med Reconstr Surg. 2013;19(1):8-12. 

14.     Shi L*, Wang S*, Zangari M, Xu H, Cao TM, Xu C, Wu Y, Xiao F, Liu Y, Yang Y, Salama M, Li G, Tricot G, Zhan F. Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance. Oncotarget. 2010 May;1(1):22-33.

15.     Chen L*, Wang S*, Zhou Y, Wu X, Entin I, Epstein J, Yaccoby S, Xiong W, Barlogie B, Shaughnessy JD Jr, Zhan F. Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma. Blood. 2010 Jan 7;115(1):61-70. IF: 15.132

16.     Wang S, Tricot G, Shi L, Xiong W, Zeng Z, Xu H, Zangari M, Barlogie B, Shaughnessy JD Jr, Zhan F. RARalpha2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma. Blood. 2009 Jul 16;114(3):600-7. IF: 15.132

17.     Zheng Y*, Cai Z*, Wang S*, Zhang X, Qian J, Hong S, Li H, Wang M, Yang J, Yi Q. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis. Blood. 2009 Oct 22;114(17):3625-8. IF: 15.132

18.     Qian J, Hong S, Wang S, Zhang L, Sun L, Wang M, Yang J, Kwak LW, Hou J, Yi Q. Myeloma cell line-derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma. Blood. 2009 Oct 29;114(18):3880-9.

19.     Xiong W, Wu X, Starnes S, Johnson SK, Haessler J, Wang S, Chen L, Barlogie B, Shaughnessy JD Jr, Zhan F. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood. 2008 Nov 15;112(10):4235-46.

20.     Wang S, Hong S, Wezeman M, Qian J, Yang J, Yi Q. Dendritic cell vaccine but not idiotype-KLH protein vaccine primes therapeutic tumor-specific immunity against multiple myeloma. Front Biosci. 2007 May 1;12:3566-75.

21.     Yang J, Qian J, Wezeman M, Wang S, Lin P, Wang M, Yaccoby S, Kwak LW, Barlogie B, Yi Q. Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell. 2006 Oct;10(4):295-307. IF: 27.407

22.     Wang S, Hong S, Yang J, Qian J, Zhang X, Shpall E, Kwak LW, Yi Q. Optimizing immunotherapy in multiple myeloma: Restoring the function of patients' monocyte-derived dendritic cells by inhibiting p38 or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells. Blood. 2006 Dec 15;108(13):4071-75. IF: 15.132

23.     Qian J, Wang S, Yang J, Xie J, Lin P, Freeman ME 3rd, Yi Q. Targeting heat shock proteins for immunotherapy in multiple myeloma: generation of myeloma-specific CTLs using dendritic cells pulsed with tumor-derived gp96. Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8808-15.

24.     Wang S, Yang J, Qian J, Wezeman M, Kwak LW, Yi Q. Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma. Blood. 2006 Mar 15;107(6):2432-9. IF: 15.132

25.     Xie J, Qian J, Yang J, Wang S, Freeman ME 3rd, Yi Q. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells. ExpHematol. 2005 May;33(5):564-72.

26.     Xie J, Qian J, Wang S, Freeman ME 3rd, Epstein J, Yi Q. Novel and detrimental effects of lipopolysaccharide on in vitro generation of immature dendritic cells: involvement of mitogen-activated protein kinase p38. J Immunol. 2003 Nov 1;171(9):4792-800.