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临床药学与药事管理学系

兰轲 副教授(博士生导师)

来源: 发布时间:2021年12月27日 点击数:

兰轲 副教授(博士生导师)

单  四川大学必赢437app登录

通讯地址成都市人民南路三段17

电子邮件lanwoco@scu.edu.cn

Researchgate: https://www.researchgate.net/profile/Ke_Lan

Publon: https://publons.com/researcher/1351267/ke-lan/

教育背景

1996.09~2001.06,四川大学必赢437app登录,临床药学,本科

2001.09~2004.06,四川大学必赢437app登录,生物药剂学,硕士研究生

2004.09~2007.06,四川大学必赢437app登录,生物药剂学,博士研究生

2007.07~2011.06,四川大学必赢437app登录,讲师

2015.03~2016.02,夏威夷大学癌症研究中心代谢组学实验室,访问学者

2011.07~,四川大学必赢437app登录,副教授

研究兴趣与方向

课题组致力于药物代谢与药物代谢组学领域的基础研究。近年来专注于重要药物代谢酶CYP3A在人类胆汁酸代谢中的生物学功能及其转化研究,获得了以下几个方面的进展:(1)阐明了人类及主要模式哺乳动物体内由CYP3A选择性催化三级胆汁酸代谢通路,提出了药物代谢酶在宿主-肠道微生物共代谢网络的生物学功能假说;(2阐明了初级胆汁酸肝脏氧化代谢及肾排泄是新生儿胆汁酸清除代谢的主要特征,发明了表征胎儿特征性CYP3A7酶活性的高特异性体外探针反应DCA19-氧化反应;(3)提出了三级胆汁酸代谢生物标志物预测CYP3A体内活性的药物代谢组学策略,并在动物体内完成了初步概念验证试验


       
 
 

 

学术兼职与荣誉

· 2021~Review Editor for Translational Pharmacology, Frontiers in Pharmacology

· 2019~:中国实验动物学会屏障医学专业委员会委员

· 2019~今:美国药理学与实验治疗学会 (ASPET)会员

· 2018Young Scientist Awards for Best Poster, 6th APISSX, Zhejiang University, Hangzhou

· 2017:第三届刘昌孝人才奖“优秀青年科技工作者奖(提名奖)”

· 2018~今:中国药理学会药物代谢专业委员会青年委员

· 2017~今:《中国临床药理学杂志》青年编委

· 2017~今:国家药品监督管理局药物临床试验检查员

· 2015~今:Editorial Board Member, Eur J Drug Metab Pharmacokinet

科研项目

· 国家自然科学基金面上项目,CYP3A在人类胆汁酸宿主-肠道微生物协同代谢中的生物学功能研究及其药物代谢组学转化探究,8207392155万,实施年限:2021.1~2024.12,负责人

· 国家自然科学基金青年科学基金项目,运用代谢组学技术系统研究乌头碱类镇痛药的体内活性/毒性代谢产物,8130284424万,实施年限:2014.1-2016.12,负责人

授权专利

1. 兰轲,徐亮,张建,黄亮,细胞色素CYP3A7酶的新型特异性探针反应及其应用,专利号:ZL 2018 1 0953793.7,专利权人:四川大学,授权日期:2021.06

2. 兰轲,徐亮,黄亮,细胞色素CYP3A7酶的特异性探针反应及其应用,专利号:ZL 2018 1 0543953.0,专利权人:四川大学,授权日期:2021.07

代表论著

在国内外公开发表药物代谢与药物代谢组学领域的论文50余篇,近年发表的代表作有:

1. 胡亦婷#, 吴清亮, 黄亮, 兰轲*. 胆汁酸Ⅱ相代谢研究进展.中国临床药理学杂志. 2021, 37(13): 1742-1748.

2. Gui LL#, Wu QL#, Hu YT, Zeng WS, Tan XW, Zhu PP, Li XJ, Yang L, Jia W, Liu CX, Lan K*. Compensatory transition of bile acid metabolism from fecal disposition of secondary bile acids to urinary excretion of primary bile acids underlies rifampicin-induced cholestasis in beagle dogs. ACS Pharmacol Transl Sci, 2021, 4(2):1001-1013. doi: 10.1021/acsptsci.1c00052

3. Zeng WS#, Gui LL#, Tan XW, Zhu PP, Hu YT, Wu QL, Li XJ, Yang L, Jia W, Liu CX, Lan K*. Tertiary oxidation of deoxycholate is predictive of CYP3A activity in dogs. Drug Metab Dispos, 2021, 49(5): 369-378. doi: 10.1124/dmd.121.000385

4. Zheng XJ#, Chen TL#, Jiang RQ#, Zhao AH, Wu Q, Kuang JL, Sun DN, Ren ZX, Li MX, Zhao ML, Wang SL, Bao YQ, Li HT, Hu C, Dong B, Li DF, Wu JY, Xia JL, Wang XM, Lan K, Rajani C, Xie GX, Lu AP, Jia WP*, Jiang CT*, Jia W*. Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism. Cell Metab, 2021, 33(4): 791-803. doi: 10.1016/j.cmet.2020.11.017

5. 丁劲松#, 王安娜#, 黄亮, 贾伟, 刘昌孝, 兰轲*. 人体熊去氧胆酸代谢及其生物等效性研究的技术挑战. 药学学报, 2020, 55(9): 2070-2079. doi: 10.16438/j.0513-4870.2020-0447

6. Wang WX#, Chen L#, Wang GY, Zhang JL, Tan XW, Lin QH, Chen YJ, Zhang J, Zhu PP, Miao J, Su MM, Liu CX, Jia W, Lan K*. Urinary bile acids profile of cesarean sectioned newborns is characterized by oxidative metabolism of primary bile acids: limited roles of fetal-specific CYP3A7 in cholate oxidations. Drug Metab Dispos, 2020, 48 (8) 662-672. doi: 10.1124/dmd.120.000011

7. Lin  QH#, Tan XW#, Wang WX, Zeng WS, Gui LL, Su MM, Liu CX, Jia W, Xu L, Lan K*. Species differences of bile acid redox metabolism: tertiary oxidation of deoxycholate is conserved in preclinical animals. Drug Metab Dispos, 2020, 48 (6) 499-507. doi: 10.1124/dmd.120.090464

8. 兰轲. 药物代谢酶CYP3A在胆汁酸宿主-肠道微生物协同代谢中的生物学功能假说. 中国临床药理学杂志. 2019, 35(22):2923-2929.

9. Chen YJ#, Zhang J#, Zhu PP, Tan XW, Lin QH, Wang WX, Yin SS, Gao LZ, Su MM, Liu CX, Xu L, Jia W, Sevrioukova IF*, Lan K*. Stereoselective oxidation kinetics of deoxycholate in recombinant and microsomal CYP3A enzymes: deoxycholate 19-hydroxylation is an in vitro marker of CYP3A7 activity. Drug Metab Dispos, 2019, 47 (6) 574-581. doi: 10.1124/dmd.119.086637

10. Zhang J#, Gao LZ#, Chen YJ, Zhu PP, Yin SS, Su MM, Ni Y, Miao J, Wu WL, Chen H, Brouwer KLR, Liu CX, Xu L, Jia W*, Lan K*. Continuum of host-gut microbial co-metabolism: CYP3A4/3A7 are responsible for tertiary oxidations of deoxycholate species. Drug Metab Dispos, 2019, 47(3): 283-294. doi: 10.1124/dmd.118.085670. (Cover Illustration)

11. Xie GX, Wang SL, Zhang H, Zhao AH, Liu JJ, Ma YM, Lan K, Ni Y, Liu CX, Liu P, Chen TL*, Jia W*. Poly-Pharmacokinetic Study of a Multicomponent Herbal Medicine in Healthy Chinese Volunteers. Clin Pharmacol Ther, 2018, 103(4):692-702. doi: 10.1002/cpt.784

12. Zhu P, Zhang J, Chen Y, Yin S, Su M, Xie G, Brouwer KLR, Liu C, Lan K*, Jia W*. Analysis of human C24 bile acids metabolome in serum and urine based on enzyme-digestion of conjugated bile acids and LC-MS determination of unconjugated bile acids. Anal Bioanal Chem. 2018, 410(21): 5287-5300. doi: 10.1007/s00216-018-1183-7

13. Yin S, Su M, Xie G, Li X, Wei R, Liu C, Lan K*, Jia W*. Factors affecting separation and detection of bile acids by liquid chromatography coupled with mass spectrometry at negative mode. Anal Bioanal Chem. 2017, 409(23):5533-5545. doi: 10.1007/s00216-017-0489-1

14. Fan X, Yin SS, Li XJ, Yang K, Xu L, Lan K*. Hydroxylation metabolisms of crassicauline A in rats under toxic dose. Eur J Drug Metab Ph, 2017, 42(5): 857-869. doi: 10.1007/s13318-017-0408-z

15. Lan K, Su M, Xie G, Ferslew BC, Brouwer KL, Rajani C, Liu C, Jia W*. Key role of 12-hydroxy group for the negative ion fragmentation of unconjugated C24 bile acids. Anal Chem, 2016, 88 (14): 7041-7048. doi: 10.1021/acs.analchem.6b00573




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