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长期潜心研究严重危害人类健康的重大神经系统疾病如脑卒中和抑郁症,围绕这两种疾病的共性病理机制-神经炎性反应,针对目前缺乏有效中枢性抗炎药物和治疗靶点等关键科学问题,聚焦表观遗传学-非编码RNA 等分子生物学前沿,取得原创成果:1)发现脑卒中显著变化的新型非编码RNA-环状RNA,并证实其临床应用价值; 2)阐明非编码RNA 独特药理作用的背后生物分子事件, 包括circRNAs 对胶质细胞异质性、血脑屏障完整性和神经元存活及可塑性等的调节作用;3)基于环状RNA精密调控网络,发现新型治疗靶点,并借助人工智能辅助设计,合成具有自主知识产权的化合物; 4)创新性探究环状RNA 与抑郁症相关性,为临床早期诊断提供客观生物学标记物,研发具有临床高灵敏性的环状RNA 试剂盒。研究成果从新的视角阐明重大神经系统疾病的病理机制,为诊疗疾病提供新思路和新型潜在药物。

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1.Zhou, Zhenhua; Lu, Jianfei; Liu, Wen-Wu; Manaenko, Anatol; Hou, Xianhua; Mei, Qiyong; Huang, Jun-Long; Tang, Jiping; Zhang, John H; Yao, Honghong; Hu, Qin. Advances in stroke pharmacology.Pharmacology & therapeutics.(Epub) 2.Yuan Zhang, Longfei Du, Ying Bai, Bing Han, Cancan He, Liang Gong,Rongrong Huang, Ling Shen, Jie Chao, Pei Liu, Hongxing Zhang, Haisan, Zhang, Ling Gu, Junxu Li, Gang Hu, Chunming Xie, Zhijun Zhang,Honghong Yao. CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination. Molecular Psychiatry. (in press) 3.Yang L, Han B, Zhang Y, Bai Y, Chao J, Hu G, Yao HH. Engagement of circular RNA HECW2 in the nonautophagic role of ATG5 implicated in the endothelial-mesenchymal transition. Autophagy. 2018;14(3):404-18. doi: 10.1080/15548627.2017.1414755. 4.Han B, Zhang Y, Zhang YH, Bai Y, Chen XF, Huang RR, Wu FF, Leng S, Chao J, Zhang JH, Hu G, Yao HH. Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy. 2018;14(7):1164-84. doi: 10.1080/15548627.2018.1458173. 5.Bai Y, Zhang Y, Han B, Yang L, Chen XF, Huang RR, Wu FF, Chao J, Liu P, Hu G, Zhang JH, Yao HH. Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood-Brain Barrier Integrity. Journal Of Neuroscience. 2018;38(1):32-50. doi: 10.1523/Jneurosci.1348-17.2017. 6.Han B, Chao J, Yao HH. Circular RNA and its mechanisms in disease: From the bench to the clinic. Pharmacology & therapeutics. 2018;187:31-44. doi: 10.1016/j.pharmthera.2018.01.010. 7.Huang RR, Zhang Y, Han B, Bai Y, Zhou RB, Gan GM, Chao J, Hu G, Yao HH. Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG. Autophagy. 2017;13(10):1722-41. doi: 10.1080/15548627.2017.1356975. 8.Zhang Y, Shen K, Bai Y, Lv X, Huang RR, Zhang W, Chao J, Nguyen LK, Hua J, Gan GM, Hu G, Yao HH. Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity. Autophagy. 2016;12(9):1538-59. doi: 10.1080/15548627.2016.1191723. 9.Liu HJ, Fang SC, Wang W, Cheng YS, Zhang YM, Liao H, Yao HH, Chao J. Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy. Particle and fibre toxicology. 2016;13. doi: ARTN 55 10.1186/s12989-016-0167-z. 10.Yao H, Ma R, Yang L, Hu G, Chen XF, Duan M, Kook Y, Niu F, Liao K, Fu MG, Hu G, Kolattukudy P, Buch S. MiR-9 promotes microglial activation by targeting MCPIP1. Nature communications. 2014;5. doi: Artn 4386 10.1038/Ncomms5386. 11.Yao HH, Yang YJ, Kim KJ, Bethel-Brown C, Gong N, Funa K, Gendelman HE, Su TP, Wang JQ, Buch S. Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. Blood. 2010;115(23):4951-62. doi: 10.1182/blood-2010-01-266221. 12.Yao HH, Duan M, Buch S. Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability. Blood. 2011;117(8):2538-47. doi: 10.1182/blood-2010-10-313593.

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