解析细胞膜新受体LRRC19在人类相关疾病发生发展过程中的作用

LRRC19 is a new transmembrane receptor，which is identified by us using bioinformatics combined with modern molecular techniques. Based on the previous studies and the established LRRC19 knockout mice, we will mainly focus on the the effect of LRRC19 on the immune cell recognization and immune regulation, renal infectious diseases such as urinary tract infections and pyelonephritis, gastricintestinal diseases such as intestinal inflammation, colitis and colon cancer, and the diseases associated with gut microbiota such as obesity and diabetes by establishing different diseases of mouse models. Meanwhile we will also explore the mechanisms of LRRC19, especially LRRC19 signal pathways in immune cells, kidney cells and intestine/colon cells using yeast hybridization, immunoprecipitation-mass, coimmunoprecipitation -western blot etc. The effect of LRRC19 on the epigenetic modification of colon cancer will be investigated by analyzing the maps of gene expression, non-coding RNA, DNA methylation and histone modification. Combined with various biological approaches, we will also explore the mechanisms of diseases associated with gut microbiota. The results will produce the important consequences not only in understaning recognization of immune cells, but also in the mechanisms of renal diseases, intestinal inflammation, colitis, colon cancer and other diseases such as obesity and diabetes.

LRRC19是由我们发现的一个新LRR蛋白家族成员，属于跨膜蛋白。此课题在前期研究工作基础上，依据自己构建的LRRC19基因敲除鼠，通过建立各种疾病模型，解析新受体LRRC19在人类相关疾病发生发展过程中的作用，重点关注LRRC19在免疫细胞识别和免疫调控、感染性肾炎肾病、肠炎、肠癌以及肠道菌群失调相关疾病如肥胖和糖尿病的作用；利用免疫沉淀结合质谱方法鉴定LRRC19的靶分子，探讨其可能的作用机制，尤其对LRRC19在免疫细胞、肾细胞、肠上皮细胞所涉及的信号途径进行系统研究；通过获得基因和非编码RNA表达谱以及表观组蛋白修饰多维动态图谱，结合各种生物信息学方法，解析LRRC19对肠炎肠癌表观遗传调控的影响；通过分析肠道菌群变化，分析LRRC19在肠道菌群失调相关疾病发生发展过程中的作用机理。研究结果不仅对理解免疫细胞识别和调控机制，而且对搞清肾炎、肠炎和其他相关疾病的发病机理有重要意义。

LRRC19是由我们发现的一个新LRR蛋白家族成员，属于跨膜蛋白。此课题在前期研究工作基础上，依据自己构建的LRRC19基因敲除鼠，通过建立各种疾病模型，解析新受体LRRC19在人类相关疾病发生发展过程中的作用，重点了关注LRRC19在感染性肾炎肾病、肠炎和肠癌疾病的发生发展的影响；探讨了LRRC19对肠道菌群的调控作用；利用免疫沉淀结合质谱方法鉴定LRRC19的靶分子，并探讨了可能的作用机制。在三个方面取得显著进展，包括，1）发现表达在肾小管上皮细胞的LRRC19，在肾清除细菌感染方面发挥决定性作用； 2）证实了表达在肠上皮细胞的LRRC19在肠炎肠癌的发生和发展过程中起关键作用；3）揭示了LRRC19在免疫细胞、肾细胞、肠上皮细胞所涉及的信号途径和调控机理。研究结果不仅对理解免疫细胞识别和调控机制，而且对搞清肾炎、肠炎和其他相关疾病的发病机理有重要意义。