申请人致力于肾脏病发病机制的研究，重点探讨肾脏固有免疫和炎性反应的调控机制，近5年主要学术成绩如下：揭示模式识别受体NOD2通过促进炎性反应，进而引起足细胞胰岛素抵抗和钙离子浓度升高，最终导致细胞损伤的机制；证明NADPH氧化酶对HuR的调控在NOD2mRNA稳定性方面的关键作用；提出PGRN通过阻断NOD2信号通路而减轻肾损伤的治疗新策略；明确HDAC4介导的乙酰化修饰在足细胞炎性与细胞稳态调控中的作用。申请人共发表SCI论文54篇(总影响因子270，第一或通讯作者论文合计超140，被引1017次，H指数22）。近5年以通讯作者在Kidney Int（3篇，2篇为当期重点推荐文章并配发专题述评）、Hypertension（封面论文）等本领域有影响期刊发表SCI论文16篇，单篇平均影响因子5.47。曾入选教育部“新世纪优秀人才”。拟开展的研究为乙酰化修饰对肾脏局部固有免疫的作用及调控机制。

Research in my laboratory focuses on the pathogenesis of kidney diseases and related molecular mechanisms by using transgenic mouse models, RNA interference, fluorescent imaging and pharmacological interventions, which may ultimately lead to the discovery of novel therapeutic targets of these diseases. The innovative achievements are: (1) We discovered unexpected functional contributions of NOD2, an intracellular pattern recognition receptor (PRR) responsible for immune activation, to the progression of kidney diseases. Our study for the first time demonstrated that NOD2 was one of the critical components of a signal transduction pathway that links renal injury to inflammation and podocyte insulin resistance in diabetic nephropathy. We further found the novel role of NOD2 in mediating Ca2+ signaling and observed that NOD2 overexpression enhanced TRPC6 expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca2+ release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis. (2) We further demonstrated that mRNA binding protein HuR contributed to the NOD2 mRNA stability, which was associated with NADPH oxidase-mediated redox signaling. (3) Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. We found that the level of PGRN was significantly reduced in the kidney in a mouse model of renal ischemia/reperfusion injury. We further observed that PGRN deficiency significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, increased tubular epithelial cell death, and tubulointerstitial neutrophil and macrophage infiltration, which were associated with, at least in part, NOD2-mediated inflammatory responses. (4) We unraveled which isoforms of histone deacetylases (HDACs) were associated with diabetic nephropathy and demonstrated that HDAC4 was one of critical components of a signal transduction pathway that links podocyte injury to inflammatory responses and autophagy. Currently, I have published 54 peer-reviewed papers including Kidney International, Hypertension and JBC, H index is 22, and the total impact factor (IF) is 270. As a corresponding author, two papers published in Kidney International were honored by editorial commentaries and one paper published in Hypertension was selected as a cover paper. I have achieved several provincial and ministerial scientific research awards and have been granted by Program for New Century Excellent Talents supported by National Education Committee of China. Based on the previous work, I will further explore the role of SIRT-mediated acetylation on the regulation of innate immune responses and inflammation in the kidney.