李靜雅

個人簡介

中國科學院上海藥物研究所研究員，博士研究生導師，研究組長。2003年于中國科學院上海藥物研究所獲藥理學博士學位，2006年曾赴澳大利亞Garvan醫學研究所進行合作研究。2003年至今在上海藥物研究所從事代謝性疾病創新藥物發現與作用機制研究等工作。先后以第一作者或通訊作者署名發表學術論文于Diabetes、Chemical Science、Diabetologia、J BiolChem、J Med Chem、ChemBioChem等國際期刊36篇，其他署名發表學術論文98篇。申請國內外發明專利42項，已獲授權發明專利18項。作為主要發明人參與研發的3個1.1類候選新藥,1項獲臨床批文（2017L5250）,均已轉讓國內藥企進行共同開發。

主持國家自然科學基金委項目、科技部重大科學研究計劃項目（課題）、中國科學院戰略性先導科技專項、上海市科委基礎重點項目等10余項，獲上海市人才發展基金、科技啟明星等人才基金3項。

工作經歷

• 2018/10－

  中國科學院上海藥物研究所，研究組長

• 2008/09－

  中國科學院上海藥物研究所，研究員

• 2005/07－2008/08

  中國科學院上海藥物研究所，副研究員

• 2003/07－2005/06

  中國科學院上海藥物研究所，助理研究員

• 
  

研究方向

專注于代謝性疾病的新病理機制、新靶標論證和新分子實體等發現研究

科研項目

• 2016/09-2020/09

  國家重大科學研究計劃項目課題，2016YFC1305505, 2型糖尿病腎病藥物新靶標和候選藥物的臨床前研究，2016/09-2020/09，在研，課題負責人。

• 2017/01-2020/12

  國家自然科學基金面上項目, 81673493, 雙靶向“線粒體偶聯效率和丙酮酸脫氫酶復合物PDC活性”策略改善高血糖癥, 2017/01-2020/12，在研，主持。

• 2015.1.1-2018.12.31

  中國科學院戰略性先導科技專項（Ａ類），長效DPP IV抑制類候選藥物HL012的臨床前個性化研究，2015.1.1-2018.12.31，在研，主持。

• 2016.7.1-2019.6.30

  上海市科學技術委員會（基礎重點），16JC1405000，新穎線粒體功能調節改善2型糖尿病，2016.7.1-2019.6.30，在研，主持。

科研成果

1）闡明小檗堿降糖作用與線粒體電子呼吸鏈復合物1活性抑制相關，提出溫和調控骨骼肌線粒體功能改善代謝性疾病的新靶向策略，論述線粒體生物合成是骨骼肌保持胰島素敏感性的關鍵；
2）肝組織因高脂負荷所致線粒體功能紊亂是肝實質細胞損傷的重要原因，通過提高細胞自噬改善線粒體質量控制是對抗高脂負荷肝細胞損傷的潛在策略；
3）基于糖代謝關鍵調控環節，系統建立分子靶向篩選-細胞功能確證-動物藥效評價的糖尿病創新藥物發現與研究平臺，成功研制3項1類糖尿病候選藥物，并獲1項臨床批件（2017L5250）。

榮譽獲獎

• 2004年

  中國藥理學會施維雅青年科學工作者獎

• 2014年

  上海市浦東新區科技進步一等獎，第7完成人

• 2015年

  上海市科技進步二等獎，第7完成人<span chinese="" quote",="" -apple-system,="" blinkmacsystemfont,="" "segoe="" ui",="" "pingfang="" sc",="" "hiragino="" sans="" gb",="" "microsoft="" yahei",="" "helvetica="" neue",="" helvetica,="" arial,="" sans-serif,="" "apple="" color="" emoji",="" ui="" symbol";"="" style="outline: 0px; box-sizing: border-box;"> 

代表論著

1. Li, BH; Zhang, M; Duan, YN; Shuai, L; Jiang, HW; Jia Li; Nan, FJ*, and Li, JY*. Pyrazolone Derivative C29 Protects Against HFD-induced Obesity in Mice via Activation of AMPK in Adipose Tissue.  Acta Pharmacologica Sinica 2020, in press

2. Sun, SM#; Xie, ZF#; Zhang, YM#; Zhang XW; Zhou CD; Yin, JP; Yu, YY; Cui, SC; Jiang, HW; Li, J; Nan, FJ*; Li JY*. AMPK Activator C24 Inhibits Hepatic Lipogenesis and Ameliorates Dyslipidemia in HFHC Diet Induced Animal Models. Acta Pharmacologica Sinica 2020, in press

3. Yu, YY; Cui, SC; Zheng, TN; Ma, HJ; Xie, ZF; Jiang, HW; Li, YF; Zhu, KX; Huang, CG; Li, J*; Li, JY*. Sarsasapogenin Improves Adipose Tissue Inflammation and Ameliorates Insulin Resistance in High-Fat Diet-Fed C57BL/6J Mice. Acta Pharmacologica Sinica 2020, in press

4. Xie, ZF; Jiang, HW; Liu, W; Zhang, XW; Chen, DK; Sun, SM; Zhou, CD; Liu, J; Bao, S; Wang, XC; Zhang, YN; Li, J; Hu, LH*; Li, JY*. The Triterpenoid Sapogenin (2α-OH-Protopanoxadiol) Ameliorates metabolic Syndrome via the Intestinal FXR/GLP-1 Axis Through Gut Microbiota Remodelling. Cell Death and Disease 2020, in press

5. Jiang, HW; Zhou, XE; Shi, JJ; Zhou, Z; Zhao, GG; Zhang, XW; Sun, YL; Suino-Powell, K ; Ma, L; Gao, H; Xu, XY; Li, J*; Li JY*; Melcher, K; Xu, H*.; Yi, W*. Identification and Structural Insight of an Effective PPARr Modulator with Improved Therapeutic Index for Anti-diabetic Drug Discovery. CHEMICAL SCIENCE, 2020, 11:2260-2268

6. Shuai, L#; Zhang, LN#; Li, BH#; Tang, CL; Wu, LY; Li, J* and Li, JY*. SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue. DIABETES, 2019, 68: 1449-1461.

7. Jiang, HW; Jin, J; Duan, YN; Xie, ZF; Li, YF; Gao, AH; Gu, M; Zhang, XW; Peng, C; Xia, CM; Dong, TC; Li, H; Yu, LF; Tang, J; Yang, F*; Li, JY* and Li, J*. Mitochondrial Uncoupling Coordinated with PDH Activation Safely Ameliorates Hyperglycemia via Promoting Glucose Oxidation. DIABETES, 2019, 68:2197-2209.

8. Wu, LY#; Xia, MF#; Duan, YN#; Zhang, LN; Jiang, HW; Hu, XB; Yan HM; Zhang, YQ; Gu, YS; Shi, HC; Li, J*; Gao, X* and Li, JY*. Berberine Promotes the Recruitment and Activation of Brown Adipose Tissue in Mice and Humans. CELL DEATH & DISEASE, 2019,10:468.

9. Li,SL#; Qin,C#; Cui,SC#; Xu,HL; Wu,FS; Wang,JW; Su,MB ; Fang,XY; Li,D; Jiao,Q; Zhang,M; Xia,CM; Zhu,LL; Wang,R; Li,J; Jiang,HL; Zhao,ZJ* ; Li, JY*; Li,HL*. Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes.  JOURNAL OF MEDICINAL CHEMISTRY 2019, 62:2348-2361.

10. Wu,LY; Zhang,LN; Li,BH; Duan,YN; Xie,ZF; Shuai,L; Li,J*; Li,JY*. AMP-activated protein kinase (AMPK) regulates energy metabolism through modulating thermogenesis in adipose tissue. FRonTIERS IN PHYSIOLOGY. 2018,9:122.

11. LT (Nie, Litong); Shuai, L (Shuai, Lin); Zhu, MR (Zhu, Mingrui); Liu, P (Liu, Ping); Xie, ZF (Xie, Zhi-Fu); Jiang, SW (Jiang, Shangwen); Jiang, HW (Jiang, Hao-Wen); Li, J (Li, Jia); Zhao, YM (Zhao, Yingming); Li, JY* (Li, Jing-Ya); Tan, MJ* (Tan, Minjia).  The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model Nie, MOLECULAR & CELLULAR PROTEOMICS 2017, 16:1324-1334

12. Li SL, Xu HL, Cui SC, Wu FS, Zhang YL, Su MB, Gong YH, Qiu SB, Jiao Q, Qin C, Shan JW, Zhang M, Wang JW, Yin Q, Xu MH, Liu XF, Wang R, Zhu LL, Li J, Xu YF, Jiang HL, Zhao ZJ*, Li JY*, Li HL*. Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H‐benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes.  JOURNAL OF MEDICINAL CHEMISTRY  2016, 59:6772-6790

13. Li YY, Yu LF, Zhang LN, Qiu BY, Su MB, Wu F, Chen DK, Pang T, Gu M, Zhang W, Ma WP, Jiang HW, Li JY*, Nan FJ*, Li J*. Novel Small-Molecule AMPK Activator Orally Exerts Beneficial Effects on Diabetic db/db Mice.TOXICOLOGY AND APPLIED PHARMACOLOGY. 2013, 273:325-334.

14. Zhang LN, Xu L, Zhou HY, Wu LY, Li YY, Pang T, Xia CM, Qiu BY, Gu M, Dong TC, Li JY*, Shen JK*, Jia Li*. A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obese by modulating energy expenditure and food intake.small-molecule AMP-activated protein kinase allosteric activator with beneficial effects in db/db mice. PLOS ONE 2013, 8(8):e72092.

15. Zhang LN, Zhou HY, Fu YY, Li YY, Wu F, Gu M, Wu LY, Xia CM, Dong TC, Li JY*, Shen JK*, Li J*. Novel Small-Molecule PGC-1α Transcriptional Regulator With Beneficial Effects on Diabetic db/db Mice. DIABETES 2013, 62:1297-1307.

16. Qiu BY, Turner N, Li YY, Gu M, Huang MW, Wu F, Pang T, Nan FJ, Ye JM, Li JY*, Li J*. A high-throughput assay for modulators of mitochondrial membrane potential identifies a novel compound with beneficial effects on db/db mice.  DIABETES 2010, 59:256-265.

17. Turner N, Li JY#, Gosby A, To S, Cheng Z, Miyoshi H, Taketo M, Cooney G, Kraegen E, David J, Hu LH*, Li J*, Ye JM*. Berberine, and its more biologically available derivative dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMPK and improve insulin action. DIABETES 2008, 57:1414-1418.

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