抗真菌药物发现及真菌耐药分子机制研究Research on antifungal drug and molecular mechanism of fungal drug resistance
曾先后主持过国家863课题,国家自然基金重点课题(3项)、国家杰出青年基金课题、国家自然基金面上课题(3项)、国家重大新药创制专项课题(3项)等,以通讯作者发表SCI论文130多篇,获得专利授权20多项,获上海市教学成果一等奖1项,上海市科技进步一等奖2项,国家科技进步二等奖1项,教育部科技进步一等奖1项。是全国统编教材“临床药物治疗学”(第1-5版)主编,主编出版“真菌感染性疾病的药物治疗”(人民卫生出版社),曾被评为上海市优秀青年教师、上海市科技启明星,上海市优秀学科带头人和上海市领军人才。主持过基金项目:
1. 国家重大新药创制专项课题(批准号2009ZX09301-011):综合性新药研究开发技术大平台,4000万元;
2. 国家重大新药创制专项课题(批准号2009ZX09102-043):调脂新药乙酰黄酮醇的临床前研究,300万元;
3. 国家自然科学基金重点项目(批准号30630071):白念珠菌耐药性产生的分子机制研究,140万元;
4. 国家杰出青年自然科学基金(批准号30825041):脂筏参与白念珠菌耐药性形成的机制研究,200万元;
5. 国家自然基金重大研究计划培育项目(批准号90913008):作用于白念珠菌CaN信号通路的寡聚酰胺小分子探针研究,50万元;
6. 国家973计划课题(批准号2013CB531600/602):重要侵袭性致病真菌与宿主相互作用的分子与细胞机制研究,2200万元;
7. 国家自然科学基金重点项目 (批准号81330083):新型抗耐药真菌化合物的作用靶点及分子机制研究,290万;
8. 国家自然科学基金面上项目 (批准号81573473):新型氨基吡啶类化合物抗真菌作用的分子机制研究,90万;
9. 国家自然科学基金国际合作重点项目(批准号 82020108032):基于化学基因组学的抗耐药真菌先导物的发现及其作用靶点研究,249万;代表性论著
1、Zhang SQ, Zou Z, Shen H, Shen SS, Miao Q, Huang X, Liu W, Li LP, Chen SM, Yan L, Zhang JD, Zhao JJ, Xu GT, An MM*, Jiang YY*.Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.PLoSPathog. 2016;12(5):e1005617.
2、Wu J#1, Ni T#2, Chai X2, Wang T2, Wang H2, Chen J2, Jin Y2, Zhang D2, Yu S*3, Jiang Y*4.Molecular docking, design, synthesis and antifungal activity study of novel triazole derivatives.Eur J Med Chem. 143(2018)1840-1846
3、Chen SM, Shen H, Zhang T, Huang X, Liu XQ, Guo SY, Zhao JJ, Wang CF, Yan L, Xu GT, Jiang YY*, An MM*. Dectin-1 plays an important role in host defense against systemic Candida glabrata infection. Virulence. 2017; 8(8): 1643–1656.
4、Li DD#, Chai D#, Huang XW, Guan SX, Du J, Zhang HY, Sun Y*, Jiang YY*.Potent In Vitro Synergism of Fluconazole and Osthole against Fluconazole-Resistant Candida albicans.Antimicrob Agents Chemother. 2017 Aug; 61(8): e00436-17.
5、Long Yang#, Wenwen Gu#, King-Ho Cheung, Lan Yan, Benjamin Chun-Kit Tong, Yuanying Jiang*, Jun Yang*. InsP3R-SEC5 interaction on phagosomes modulates innate immunity to Candida albicans by promoting cytosolic Ca2+ elevation and TBK1 activity. BMC Biol. 2018; 16: 46
6、LvQZ, Qin YL, Yan L*, Wang L, Zhang C, Jiang YY*. NSG2 (ORF19.273) Encoding Protein Controls Sensitivity of Candida albicans to Azoles through Regulating the Synthesis of C14-Methylated Sterols. Front Microbiol. 2018 Feb 20;9:218.
7、Xu Y, Quan H, Wang Y, Zhong H, Sun J, Xu J, Jia N*, Jiang Y*. Requirement for Ergosterol in Berberine Tolerance Underlies Synergism of Fluconazole and Berberine against Fluconazole-Resistant Candida albicans Isolates. Front Cell Infect Microbiol. 2017 Nov 29;7:491.
8、Li LP, Wang XJ, Zhang JY, Zhang LL, Cao YB, Gu LQ, Yu YQ, Yang QL, Shen CY, Han B*, Jiang YY*.Antifungal activity of osthol in vitro and enhancement in vivo through Eudragit S100 nanocarriers.Virulence. 2018; 9(1): 555–562.
9、Zhong H, Hu DD, Hu GH, Su J, Bi S, Zhang ZE, Wang Z, Zhang RL, Xu Z, Jiang YY*, Wang Y*.Activity of sanguinarine against Candida albicans biofilms.Antimicrob Agents Chemother. 2017 May; 61(5): e02259-16.
10、Liu W, Zou Z, Huang X, Shen H, He LJ, Chen SM, Li LP, Yan L, Zhang SQ, Zhang JD, Xu Z, Xu GT, An MM*, Jiang YY*. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins. Sci Rep. 2016 Oct 6;6:34854.
11、Liao Z, Yan Y, Dong H, Zhu Z, Jiang Y*, Cao Y*.Endogenous nitric oxide accumulation is involved in the antifungal activity of Shikonin against Candida albicans.Emerg Microbes Infect. 2016 Aug 17;5(8):e88.
12、 Lu H, Shrivastava M, Whiteway M*, Jiang Y*. Candida albicans targets that potentially synergize with fluconazole. Crit Rev Microbiol. 2021 May;47(3):323-337.
13、Quan-Zhen Lv, De-Dong Li, Hua Han, Yi-Heng Yang, Jie-Lin Duan, Hui-Hui Ma, Yao Yu, Jiang-Ye Chen, Yuan-Ying Jiang*, Xin-Ming Jia*. Priming with FLO8-deficient Candida albicans induces Th1-biased protective immunity against lethal polymicrobial sepsis. Cell Mol Immunol. 2020 Nov 5 : 1–14.
14、Si-Min Chen, Zui Zou, Shi-Yu Guo, Wei-Tong Hou, Xi-Ran Qiu, Yu Zhang, Li-Jun Song, Xin-Yu Hu, Yuan-Ying Jiang*, Hui Shen*, Mao-Mao An*. Preventing Candida albicans from subverting host plasminogen for invasive infection treatment. Emerg Microbes Infect. 2020; 9(1): 2417–2432.
15、Xin Huang, Yu Liu, Tingjunhong Ni, Liping Li, Lan Yan, Maomao An, Dazhi Zhang*, Yuanying Jiang*. 11g, a Potent Antifungal Candidate, Enhances Candida albicans Immunogenicity by Unmasking β-Glucan in Fungal Cell Wall. Front Microbiol. 2020, Jun 30; 11: 1324.
16、Lu RY, Ni TJ, Wu J, Yan L, Lv QZ, Li LP, Zhang DZ*, Jiang YY*. New Triazole NT-a9 Has Potent Antifungal Efficacy against Cryptococcus neoformans In Vitro and In Vivo. Antimicrob Agents Chemother. 2020 Jan 27;64(2). pii: e01628-19.
17、Liao Z, Zhu Z, Li L, Wang L, Wang H, Jiang Y*, Cao Y*. Metabonomics on Candida albicans indicate the excessive H3K56ac is involved in the antifungal activity of Shikonin. Emerg Microbes Infect. 2019;8(1):1243 -1253.成果奖励:
1、新时期军事特色药学人才培养模式的研究与实践,上海市教学成果奖一等奖,2009年,第一完成人;
2、抗乙肝病毒新晶型阿德福韦酯的研发及产业化,上海市科学技术进步奖,一等奖,2013年,第三完成人;
3、重要疑难真菌病及皮肤病的诊治研究,上海市科学技术进步奖,一等奖,2014年,第二完成人;
4、重要真菌病的临床诊治与干预策略,国家科学技术进步奖,二等奖,2015年,第三完成人;
5、抗真菌药物研发创新体系的建立与应用,教育部科学技术进步奖,一等奖,2020年,第二完成人;
6、姜远英,上海市领军人才,2016年;