申请人主要致力于代谢性疾病所致足细胞损伤机制研究。主要研究发现：（1）首次提出了足细胞脂筏-氧化还原信号平台的概念，并阐明了其在高同型半胱氨酸血症所致足细胞损伤中的作用；（2）发现NADPH氧化酶介导的NLRP3 炎症小体活化是糖尿病肾病足细胞损伤和蛋白尿发生的新机制；（3）从蛋白尿发生的后果入手，阐明了蛋白过负荷对足细胞的损伤作用及机制。近5年，以第一/通讯作者发表SCI收录论文20篇，累计影响因子约81。. 细胞周期紊乱是糖尿病肾病足细胞损伤和缺失的重要机制。我们的前期研究发现，MAD2B是介导高糖所致足细胞细胞周期紊乱的关键分子，且已通过酵母双杂交方法找到一种新的MAD2B相互作用蛋白----Numb。我们将在此基础上，以DN患者、足细胞条件性MAD2B基因敲除小鼠和体外高糖刺激的足细胞为研究对象，深入探讨MAD2B在糖尿病肾病足细胞损伤中的作用及其机制。

The research interest of the applicant is metabolic diseases-induced podocyte injury. Our findings include：(1) proposed the concept of “lipid-raft redox signaling platform” and elucidated its pathogenic role in hyperhomocysteinemia-associated podocyte injury; (2) proved the role of NADPH oxidase-mediated NLRP3 inflammasome activation in the pathogenesis of high glucose-induced podocyte injury; (3) clarified the mechanism of protein overload-induced podocytes injury. In the last 5 years, the applicant published 20 papers in SCI-indexed journals as first or corresponding author. The total impact factor of these papers is approximately 81. . The abnormality of cell cycle is one of the main mechanisms leading to podocyte injury and depletion during diabetic nephropathy. Recently, we found that MAD2B (mitotic arrest deficient-like 2) is an important molecule involved in the pathogenesis of diabetic nephropathy. Our preliminary data from yeast two-hybrid system showed that MAD2B interacted with Numb, which shed light on the understanding the pathogenic role of MAD2B. In future research, we will continue to explore the functional mechanisms of MAD2B in the pathogenesis of podocyte injury during diabetic nephropathy.