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更新日期：2024年10月19日
姓 名 刘靖华 性 别 女
民 族 汉族 导师层次 博士导师
技术职称 教授 导师类型 学术型
最后学历 博士研究生毕业 最后学位 无学位
行政职务 副主任 Email liujhua@smu.edu.cn
工作单位 基础医学院 邮政编码 510515
个人简介

刘靖华，博士，教授，博士生导师。现任南方医科大学基础医学院病理生理学教研室副主任。是中国研究型医院休克与脓毒症专业委员会常务委员、中国病理生理学受体与细胞信号转导专业委员会委员、广东省病理生理学会危重病医学专业委员会副主任委员、广东省病理生理学会理事、《中国病理生理杂志》、《感染、创伤、修复杂志》编辑委员会委员。曾公派美国匹兹堡大学、爱尔兰国立大学留学。主要研究方向是炎症的细胞信号转导、脓毒症的发生机制及防治措施。先后主持多项国家自然科学基金、广东省自然科学基金重点项目，另外还作为主要骨干参加了国家“973”计划（国家重点基础研究发展计划）项目、长江学者和创新团队发展计划、国家自然科学基金委员会-广东省人民政府自然科学联合基金重点项目等的研究工作，在Frontiers in immunology、Journal of Immunology、 Journal of Biological Chemistry、Shook等杂志发表论文100余篇，为研究生及本科生编写实验教材“现代分子生物学模块实验指南”1部（副主编，高等教育出版社），参编论著2部（科学出版社），本科生教材1部。获军队科技进步二等奖1项（第五名），国家发明专利1项（第四名）。

研究领域
研究领域主要集中在脓毒症的发生机制、细菌脂蛋白（BLP）耐受保护机制及炎症的细胞信号转导方面。
1. 长期从事脓毒性休克的机制研究。在国家自然科学基金面上项目“基于蛋白质组学技术研究内毒素休克的分子机制”（项目编号30670829，2007-2009 年，负责人刘靖华）的资助下，我们用蛋白质液相分离结合质谱技术从蛋白质组学的角度探讨了内毒素休克的发生机制。我们发现，小鼠内毒素休克后其肝组织多个组蛋白家族成员，包括组蛋白1（Histon1，H1）、组蛋白2 的A（H2A）和B（H2B）型、组蛋白4（H4）的等电点发生了显著变化。以往的研究表明蛋白质等电点的迁移主要来源于翻译后修饰，如乙酰化（acetylation）磷酸化（phosphorylation）和泛素化(ubiquitylation)等，并且越来越多的研究结果表明，组蛋白的翻译后修饰对基因的转录和表达发挥至关重要的作用。我们在上述发现的同时，在对鉴定的内毒素休克前后差异蛋白质进行功能信息的分析中还发现了一些参与甲基化和乙酰化反应的蛋白质（酶）。这些结果提示我们，内毒素休克进程中，可能通过组蛋白密码机制，使细胞的转录加强，炎症介质的释放增加。
   在上述工作的基础上，我们对内毒素刺激后组蛋白的修饰特征进行了探索，并验证了前期发现的乙酰化和甲基化修饰酶及其在内毒素炎症反应中的作用，该部分研究工作获得国家自然科学基金面上项目“组蛋白修饰对内毒素血症炎症介质释放的特异性调控”（项目编号81072425，2011-2013 年，负责人刘靖华）的资助。该项目利用染色质免疫沉淀技术(ChIP)、实时定量PCR、Western blot 和RNAi 等分子生物学手段探索了与基因特异性调控有关的组蛋白3（H3），H4 组蛋白的乙酰化和甲基化修饰特征；探讨了已发现的修饰酶SETD4（SET domain containing 4）在内毒素休克中的作用。结果提示SETD4 通过调控炎性细胞因子的释放参与了内毒素血症的发生与发展。该部分研究工作获得国家自然科学基金面上项目“甲基化转移酶SETD4调控炎症因子释放的分子机制研究”（项目编号81471901，2015-2018 年，负责人刘靖华）的资助。本项目的研究结果对于丰富组蛋白修饰的机制，进一步阐明炎症反应及内毒素休克的发生机理，探索更合理有效的抗炎措施都具有重要的理论指导意义和实践价值。
2. 近年来在细菌脂蛋白（BLP）耐受保护脓毒症小鼠的机制方面开展了一系列工作。
    首先，揭示了BLP耐受过程中BLP介导的细胞信号转导通路发生了改变，即再程序化（reprogramming），如TLR2表达水平下调、MyD88结合IRAK1的能力下降、MAPK磷酸化程度降低、NF-κB的活性受抑制等，提示上述信号事件的改变可能是BLP耐受时细胞（机体）炎症介质的释放减少的主要原因。
    其次，发现BLP诱导的耐受不依赖于ST2分子。以往的研究报道，作为TOLL/IL-1受体超家族成员之一的ST2受体，是TLR4信号通路的负调控因子，同时在LPS耐受中发挥了重要的作用。我们发现，尽管ST2是TLR2信号通路的负调控因子，BLP耐受的形成不依赖于ST2受体。这些发现进一步支持“BLP耐受与LPS耐受的机制不同”的观点。
    接下来，探索了BLP耐受机体（细胞）对病原菌清除能力增强的的分子机制。在国家自然科学基金“NF-kB p65 活化在调控细菌脂蛋白耐受巨噬细胞杀菌能力中的作用及其相关分子机制”（项目编号81272149，2013-2016年，负责人刘靖华）的资助下，发现NF-kB信号通路的激活对于BLP耐受巨噬细胞增强的杀菌活性至关重要，进一步研究还发现，胞浆内模式识别受体NOD1和NOD2参与了BLP耐受巨噬细胞细菌刺激后诱导的NF-kB信号通路的激活以及随后杀菌活性增强的过程。Rab20、Acp5等分子在BLP耐受巨噬细胞表达显著增加，参与了吞噬体成熟（杀灭细菌）的过程。
 
个人成果
  1. Yantong Wan, Jinxi Liu, Yiyin Mai, Yinghao Hong, Zixuan Jia, Guijie Tian, Yunzhuo Liu, Huaping Liang & Jinghua Liu. Current advances and future trends of hormesis in disease. NPJ Aging. 2024, doi.org/10.1038/s41514-024-00155-3
  2. Jiafu Ouyang, Yinghao Hong, Yantong Wan, Xiangyi He, Bingxuan Geng, Xinxing Yang, Jing Xiang, Junwei Cai, Zhenhua Zeng, Zhifeng Liu, Na Peng, Yong Jiang, Jinghua Liu. PVB exerts anti-inflammatory effects by inhibiting the activation of MAPK and NF-κB signaling pathways and ROS generation in neutrophils. International Immunopharmacology. 2024,126:111271.
  3. Chong Wang, Tao Wang, Kang-Jing Li, Ling-Hong Hu, Yue Li, Yu-Zhong Yu, Tao Xie, Sha Zhu, Du-Jiang Fu, Yang Wang, Xian-Zi Zeng, Feng-Ping Liu, Hong Chen, Zhe-Sheng Chen, Ning-Han Feng, Jinghua Liu, Yong Jiang, Shan-Chao Zhao, SETD4 inhibits prostate cancer development by promoting H3K27me3-mediated NUPR1 transcriptional repression and cell cycle arrest, Cancer Letters, 2023, 216464, ISSN 0304-3835.
  4. Yantong Wan, Junyi Shen, Yinghao Hong, Peng Dong, Lixin Liang, Jinghua Liu, Tieliu Shi and Junwei Cai. Mapping knowledge landscapes and emerging trends of the biomarkers in melanoma: Front Oncol. 2023; 13: 1181164. doi: 10.3389/fonc.2023.1181164
  5. Jingyi Jin, Yantong Wan, Qiang Shu, Jinghua Liu, Dengming Lai. Knowledge mapping and research trends of IL-33 from 2004 to 2022: a bibliometric analysis. Front Immunol. 2023, 20;14:1158323. doi:10.3389/fimmu.2023.1158323
  6. Na Peng, Yan Geng, Jiafu Ouyang, Shuai Liu, Fangfang Yuan, Yantong Wan, Wenda Chen, BaoJun Yu, Youqing Tang, Lei Su, Huaping Liang, Jiang Huai Wang and Jinghua Liu. Endothelial glycocalyx injury is involved in heatstroke-associated coagulopathy and protected by N-acetylcysteine. Front Immunol. 2023, 6;14:1159195. doi: 10.3389/fimmu.2023.1159195.
  7. Xiangjun Ji, Junwei Cai, Lixin Liang, Tieliu Shi and Jinghua Liu. Gene expression variability across cells and species shapes the relationship between renal resident macrophages and infiltrated macrophages. BMC Bioinformatics 24, 72 (2023). https://doi.org/10.1186/s12859-023-05198-z
  8. Yantong Wan, Junyi Shen, Jiafu Ouyang, Peng Dong, Yinghao Hong, Lixin Liang, Jinghua Liu. Bibliometric and Visual Analysis of Neutrophil Extracellular Traps from 2004 to 2022，Front. Immunol. 13:1025861. doi: 10.3389/fimmu.2022.1025861
  9. Piao Luo, Qian Zhang, Tian‑Yu Zhong, Jia‑Yun Chen1, Jun‑Zhe Zhang, Ya Tian, Liu‑Hai Zheng, Fan Yang, Ling‑Yun Dai, Chang Zou, Zhi‑Jie Li, Zhijie Li, Jinghua Liu, Ji‑Gang Wang. Celastrol mitigates infammation in sepsis by inhibiting the PKM2-dependent Warburg effect . Military Medical Research. 2022, 22(9):1-16.
  10. Jingjing Ji, Zhifeng Liu, Xinxin Hong, Zheying Liu, Jinghua Gao, Jinghua Liu. Protective effects of rolipram on endotoxic cardiac dysfunction via inhibition of the inflammatory response in cardiac fibroblasts. BMC Cardiovasc Disord. 2020, 20(1):242 DOI:10.1186/s12872-020-01529-7.
  11. Hanhui Zhong, Haitao Lin, Qiongni Pang, Jinling Zhuang, Xiaolei Liu, Xiaolian Li, Jinghua Liu, Jing Tang. Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia. Inflammation Research. 2021, 70(2):193-203.
  12. Wenting Chen, Shuqi Zhao, Michael Ita, Yue Li, Jingjing Ji, Yong Jiang, H. Paul Redmond, Jiang Huai Wang, and Jinghua Liu. An early neutrophil recruitment into the infectious site is critical for BLP tolerance-afforded protection against microbial sepsis. Journal Immunology. 2020, 204(2):408-417.
  13. Shuqi Zhao, Dalin Xi, Junwei Cai, Wenting Chen, Jing Xiang, Na Peng, Juan Wang, Yong Jiang, Zhuzhong Mei, Jinghua Liu. Rab20 is critical for bacterial lipoprotein tolerization-enhanced bactericidal activity in macrophages during bacterial infection. Sci China Life Sci. 2020, 63(3):401-409.
  14. Yuyun Zhong, Ping Ye, Zhuzhong Mei, Sui Huang, Mengyi Huang, Li Yue, Shixian Niu, Shuqi Zhao, Junwei Cai, Juan Wang, Yong Jiang, Jinghua Liu. The novel methyltransferase SETD4 regulates TLR agonist-induced expression of cytokines through methylation of lysine 4 at histone 3 in macrophages. Molecular Immunology. 2019, 114(7):179-188.
  15. Yue Li, Shixian Niu, Dalin Xi, Shuqi Zhao, Jiang Sun, Yong Jiang, Jinghua Liu. Differences in LPS-induced inflammatory response between MEFs and BMDMs. J Interferon Cytokine Res. 2019, 39(6):375-382.
  16. Shuqi Zhao, Yuyun Zhong, Xiaoxia Fu, Yiqian Wang, Ping Ye, Junwei Cai, Yun Liu, Jiang Sun, Zhuzhong Mei, Yong Jiang, Jinghua Liu. H3K4 methylation regulates LPS-induced proinflammatory cytokine expression and release in macrophages. Shock. 2019, 51(3):401-406.
  17. Zhu Zhong Mei, Hongwei Sun, Xiaoli Ou, Lei Li, Junwei Cai, Shuiwang Hu, Juan Wang, Haihua Luo, Jinghua Liu, Yong Jiang. The natural antisense transcript NATTD regulates the transcription of decapping scavenger (DcpS) enzyme. Int J Biochem Cell Biol. 2019,110(3):103-110.
  18. Wenting Chen, Hanhui Zhong, Xiaofei Wang, Qiongni Pang, Jinling Zhuang, Jian Hu, Yeming Chen, Jijie Hu, Jinghua Liu, Jing Tang. Mig6 reduces inflammatory mediators production by regulating the activation of EGFR in LPS-induced endotoxemia. J Cell Physiol. 2018, 233(9):6975-6983.
  19. Jinghua Liu, Jing Xiang, Xue Li, Siobhan Blankson, Shuqi Zhao, Junwei Cai, Yong Jiang, H. Paul Redmond, Jiang Huai Wang. NF-kB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection. Sci. Rep. 2017, 1, 7:40418 | DOI: 10.1038/srep40418.
  20. Jinghua Liu, Juan Wang, Haihua Luo, Zhijie Li, Tianyu Zhong, Jing Tang, Yong    Jiang. Screening cytokine/chemokine profiles in serum and organs from an endotoxic shock mouse model by LiquiChip. Sci China Life Sci, 2017, 60(11):1242-1250.
  21. Zhigang Li, Erica K Fan, Jinghua Liu, Melanie J Scott, Yuehua Li, Song Li, Wen Xie, Timothy R Billiar, Mark A Wilson, Yong Jiang, Ping Wang, and Jie Fan Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma. Cell Death Dis. 2017; 8(5): e2775.
  22. Zhigang Li, Melanie J. Scott, Erica K. Fan, Yuehua Li, Jinghua Liu, Guozhi Xiao, Song Li, Timothy R. Billiar, Mark A. Wilson, Yong Jiang, Jie Fan. Tissue damage negatively regulates LPS-induced macrophage necroptosis. Cell Death Differ. 2016, 23(9):1428-47.
  23. Zhuzhong Mei, Xinyu Chen, Shuiwang Hu, Ni wang, Xiaoli Ou, Jingwang, Haihua Luo, Jinghua Liu, Yong Jiang. Kelch-like protein 21 (KLHL21) targets IκB kinase-β to regulate nuclear factor κ-light chain enhancer of activated B cells (NF-κB) signaling negatively. J Bio Chem. 2016, 291(35):18176-89.
  24. Andrew P. Coveney, Wei Wang, Justin Kelly, Jing Hua Liu, Siobhan Blankson, Qiong Di Wu, H. Paul Redmond, Jiang Huai Wang. Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways. Sci. Rep. 2015, 5, 13694; doi: 10.1038/srep13694.
  25. Zhifeng Liu, Jinghua Liu, Juan Wang, Jia Xu, Yawei Liu, Xuegang Sun, Lei Su, Jiang Huai Wang and Yong Jiang. Role of testis specific high mobility group protein in transcriptional regulation of inducible nitric oxide synthase expression in the liver of endotoxic shock mice, FEBS J. 2014, 281(9): 2202–2213.
  26. Chong Hui Li, Jinghua Liu, Mingbang An, H Paul Redmond, Jiang Huai Wang. Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1. Immunol Cell Biol. 2012, 90(3):314–20.
  27. Julliette M. Buckley, Jinghua Liu, Chong Hui Li, SiobhanBlankson, Qiong Di Wu, Yong Jiang, H.Paul Redmond, Jiang Huai Wang. Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function. J Immunol. 2011, 187(8):4293-9.
  28. Jinghua Liu, Julliette M. Buckley, H. Paul Redmond, Jiang Huai Wang. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance. J Immunol. 2010, 184(10):5802-8.