课题组负责人

温振科博士，博导

www.优德88.cpm 特聘教授

生物医学研究院执行院长

温振科博士，山东人；2004年毕业于山东第一医科大学、获临床医学学士学位，2007年毕业于复旦大学上海医学院、师从熊思东教授获免疫学硕士学位，2007-2010年在青岛市中心血站输血医学研究所任医师、副所长，随即在复旦大学上海医学院师从熊思东教授攻读免疫学博士学位，2013年博士毕业后在美国西奈山医学院和斯坦福大学做Postdoc和Research Scientist；2019年9月加盟www.优德88.cpmIBMS任教授、课题组长，荣获国家海外高层次人才青年项目、江苏特聘教授、江苏省杰青和姑苏创新创业领军人才；现任IBMS执行院长、江苏省感染与免疫重点实验室主任。

研究方向

核酸抗原适应性免疫是尚未解决的免疫学基本科学问题。

我们聚焦核酸抗原—自身DNA的适应性免疫，依托临床患者与对照人群队列、人源化疾病模型、人源组织类器官和疾病相关细胞互作平台，深入研究：

（1）自身DNA适应性免疫识别与应答的细胞和分子基础；

（2）自身DNA调控T/B细胞分化与功能的分子机制及其干预；

（3）自身DNA重塑组织器官区域免疫特性的作用基础及应对策略。

近期主要成果（^*Co-first,^#Corresponding）

1.Hu C, Qiao W, Li X, Ning ZK, Liu J, Dalangood S, Li H, Yu X, Zong Z^#,Wen Z^#, Gui J^#. Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8+T cells.Cell Metab2024 Jan 23:S1550-4131(24)00006-8.

2. Wang Y, Liu M, Zhang L, Liu X, Ji H, Wang Y, Gui J^#, Yue Y^#,Wen Z^#. Cancer CD39 drives metabolic adaption and mal-differentiation of CD4+ T cells in patients with non-small-cell lung cancer.Cell Death Dis2023; 14(12):804.

3. Qiao W, Hu C, Ma J, Dong X, Dalangood S, Li H, Yuan C, Lu B, Gao WQ,Wen Z^#, Yin W^#, Gui J^#. Low-dose metronomic chemotherapy triggers oxidized mtDNA sensing inside tumor cells to potentiate CD8+T anti-tumor immunity.Cancer Lett2023; 216370.

4.Liu Z, Lei J, Wu T, Hu W, Zheng M, Wang Y, Song J, Ruan H, Xu L, Ren T^#, Xu W^#,Wen Z^#. Lipogenesis promotes mitochondrial fusion and maintains cancer stemness in human NSCLC.JCI Insight2023; 8(6):e158429.

5.Liu Z, Shan S, Yuan Z, Wu F, Zheng M, Wang Y, Gui J, Xu W, Wang C^#, Ren T^#,Wen Z^#. Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells.EMBO Rep2023; 24(2):e54006.

6.Jiang W, Sun M, Wang Y, Zheng M, Yuan Z, Mai S, Zhang X, Tang L, Liu X^#, Wang C^#,Wen Z^#. Critical Role of Notch-1 in Mechanistic Target of Rapamycin Hyperactivity and Vascular Inflammation in Patients With Takayasu Arteritis.Arthritis Rheumatol2022; 74(7):1235-1244.

7.Wen Z^#, Xu L, Xu W, Xiong S^#. Retinoic Acid Receptor-Related Orphan Nuclear Receptor γt Licenses the Differentiation and Function of a Unique Subset of Follicular Helper T Cells in Response to Immunogenic Self-DNA in Systemic Lupus Erythematosus.Arthritis Rheumatol2021; 73(8):1489-1500.

8.Jin K,Wen Z, Wu B, Zhang H, Qiu J, Wang Y, Warrington KJ, Berry GJ, Goronzy JJ, Weyand CM. NOTCH-induced rerouting of endosomal trafficking disables regulatory T cells in vasculitis.J Clin Invest2021; 131(1):e136042.

9.Zhang J, Zhao L, Wang J, Cheng Z, Sun M, Zhao J, Liu B, Liu X^#,Wen Z^#, Li Z^#. Targeting Mechanistic Target of Rapamycin Complex 1 Restricts Proinflammatory T Cell Differentiation and Ameliorates Takayasu Arteritis.Arthritis Rheumatol2020; 72(2):303-315.

10.Li Y, Shen Y, Jin K,Wen Z, Cao W, Wu B, Wen R, Tian L, Berry GJ, Goronzy JJ, Weyand CM. The DNA Repair Nuclease MRE11A Functions as a Mitochondrial Protector and Prevents T Cell Pyroptosis and Tissue Inflammation.Cell Metab2019; 30(3):477-492.

11.Wen Z, Jin K, Shen Y, Yang Z, Li Y, Wu B, Tian L, Shoor S, Roche NE, Goronzy JJ, Weyand CM. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation.Nat Immunol2019; 20:313-325.

12.Wen Z, Shen Y, Berry G, Shahram F, Li Y, Watanabe R, Liao YJ, Goronzy JJ, Weyand CM. The microvascular niche instructs T cells in large vessel vasculitis via the VEGF-Jagged1-Notch pathway.Sci Transl Med2017; 9(399). pii: eaal3322.

13.Shen Y,Wen Z, Li Y, Matteson EL, Hong J, Goronzy JJ, Weyand CM. Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells.Nat Immunol2017; 18(9):1025-1034.

14.Wen Z^*, Shimojima Y^*, Shirai T, Li Y, Ju J, Yang Z, Tian L, Goronzy JJ, Weyand CM. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs.J Clin Invest2016; 126:1953-67.

15.Li Y, Shen Y, Hohensinner P, Ju J,Wen Z, Goodman SB, Zhang H, Goronzy JJ, Weyand CM. Deficient activity of the nuclease MRE11A induces T cell aging and promotes arthritogenic effector functions in patients with rheumatoid arthritis.Immunity2016; 45:903-916.

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