研究方向:
1.膀胱尿路上皮屏障发育和先天遗传疾病
以基因编辑小鼠和非人灵长类等哺乳动物为模式,通过单细胞测序、空间转录组和分化诱导RNA测序筛序候选基因,然后通过基因克隆、基因编辑和遗传分析来研究基因功能,通过蛋白定位和功能域鉴定等生化手段分析分子机制,从环境因素、遗传和表观遗传来揭示膀胱尿路上皮细胞分化的关键因子和步骤,鉴定上皮细胞的关键细胞类型及其功能,以及相关的先天疾病发病机理。
图一 膀胱组织和病变
图二 膀胱尿路上皮发育和先天遗传疾病
2.尿路感染和宿主防御
以尿路感染病原菌、基因编辑小鼠和人膀胱上皮细胞系为模式,运用病原菌菌株筛选、细菌遗传突变、宿主细胞感染反应、小分子化合物等技术方法,筛选细菌毒力因素,研究宿主对毒力因子的识别防御应答机制;研究宿主先天免疫识别病原体的机制和免疫原理;筛选病原菌的耐药基因及潜在的抗生素,研究抗生素耐药的机理及防治策略。
图三 尿路感染和宿主防御
3.膀胱癌的发生和防控机制
以烟草提取物诱发膀胱尿路上皮癌模型结合基因编辑小鼠、人类膀胱上皮癌细胞系和临床膀胱上皮癌样本为模式,利用TCGA数据库、生化遗传分析、代谢分析和生物信息分析,筛选膀胱癌原癌基因和抑癌基因,并研究其作用机制。此外,通过小分子抑制剂或激活剂筛选,结合云南特色的天然及少数民族化合物库,探索膀胱癌的控制策略。
图四 膀胱上皮癌及功能鉴定
课题成员
1. Guo CM#, Zhang Y, Tan R, Tang Z, Lam CM, Ye X, Wang Z, Li X. Arid1a regulates bladder urothelium formation and maintenance. Dev Biol 2022 Mar 10;485:61-69
2. Park S., Fong K., Kim J., Wang F. , Lu X., Lee Y., Brea L., Wadosky K., Guo CM., Abdulkadir S., Crispino J., Fang D., Ntziachristos P., Liu X., Li X., Wan Y.,Goodrich D., Zhao J. and Yu J. Posttranslational regulation of FOXA1 by Polycomb and BUB3/USP7 deubiquitin complex in prostate cancer. Science Advances; 2021 Apr 7(15):eabe2261
3. Wang W#, Guo CM#, Sun K Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition? Frontiers in Physiology 2020 2020;25;11:462
4. Chen C., Zhang J., Xia H., Zhang H., Betran A.P., Zhang L., Hua X., Feng L., Chen D., Sun K., Guo CM, Qi H., Duan T., Zhang J. Preterm Birth in China Between 2015 and 2016. American Journal of Public Health; 2019 Nov;109(11):1597-1604
5. Guo CM#, Balsara Z#, Warren H, Li X* Stage- and Subunit-specific Functions of Polycomb Repressive Complex 2 in Bladder Urothelial Formation and Regeneration Development 2017 Feb 1;144(3):400-408.
6. Guo CM Does Dietary Fatty Acid, Decanoic Acid, Prevent Polycystic Ovary Syndrome? Endocrinology 2016 157(1):46-7.
7. Liu C, Guo CM, Wang W, Zhu P, Li W, Mi Y, Myatt L, Sun K. Inhibition of lysyl oxidase by cortisol regeneration in human amnion: Implications for rupture of fetal membranes. Endocrinology 2016 Aug 157(10):4055-4065.
8. Sui X, Liang X, Chen L, Guo CM, Han W, Pan H, Li X Bacterial xenophagy and its possible role in cancer: a potential antimicrobial strategy for cancer prevention and treatment. Autophagy. 2016 Dec 13(2):237-247.
9. Guo CM#, Kaneko S#, Sun Y#, Huang Y, Vlodavsky I, Li X, Li ZR*, Li X*. A Mouse Model of Urofacial Syndrome with Dysfunctional Urination. Hum Mol Genet 2015 April 1;24(7):1991-9
10. Wang W, Guo CM, Zhu P, Lu JW, Li WJ, Liu C, Xie HL, Myatt L, Chen ZJ, Sun K. Phosphorylation of STAT3 mediates the induction of cyclooxygenase-2 by co...
邮箱:chunmingguo#ynu.edu.cn