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李媛媛博士，中科中山药物创新研究院研究员、课题组长、博士生导师。入选国家重大人才工程青年人才计划、中国科学院海外高层次引进人才、上海市浦江人才、上海市领军人才(海外)、广东省珠江青年拔尖人才、中山市紧缺适用高层次人才（第二层次）等多个国家及省市人才计划。长期从事代谢相关脂肪性肝病（MASLD）、肝纤维化、动脉粥样硬化、糖尿病等重大代谢慢病的致病新机制研究、原创靶点发现及创新药物开发，具有丰富研究经验。

基础研究：已发表学术论文31篇，包括在Nature Metabolism, Hepatology（2篇）, Arteriosclerosis, Thrombosis, and Vascular Biology等代谢领域权威杂志以第一或通讯作者发表15篇文章；在 Cell Metabolism, Nature Communications, Diabetes（3篇）以共同作者发表文章16篇。发表文章得到Nature Reviews Endocrinology、Hepatology、Diabetes 等杂志的高度评价和Faculty1000 肝病领域权威专家的推荐。文章总引用超过1900次，H-index 24。在多个权威国际会议上发言且获得科研奖励，获得美国肝病研究协会 (AASLD) “青年学者奖”、2016年AASLD年会“杰出海报奖”、美国华人心血管协会口头汇报优秀奖、上海市优秀毕业生等。

新药研发：从博士开始一直从事创新药物开发，参与或主导多个与国内外大公司新药合作开发项目，如江苏恒瑞、罗氏中国、美国Intercept公司、美国Ionis公司等。参与申请并获批多个新药专利、参与1个新药项目拿到临床批件，参与多个项目实现成果转化。

基金项目：目前主持包括国家重大人才工程青年人才项目、中国科学院海外高层次引进人才择优资助项目、上海市浦江人才项目、国家自然科学基金（青年及面上项目）、广东省自然科学基金面上项目、中科中山药物创新研究院课题组长启动经费等多个科研基金项目，参与中山市代谢性疾病创新团队项目等。

学术经历：

2000-2004  华中科技大学同济医学院 药学学士

2004-2010  中国科学院上海药物研究所（保送，硕博连读） 理学博士

2010-2012  美国约翰霍普金斯大学医学院 博士后

2012-2018  美国东北俄亥俄医科大学 博士后

2019-2020 美国贝勒医学院 博士后

2020-至今 中科中山药物创新研究院 研究员/课题组长

本实验室聚焦发病机制密切相关的几类重大代谢慢病：代谢相关脂肪性肝病（MASLD）、肝纤维化和动脉粥样硬化，开展其致病新机制研究（包括共病机制）、新靶标发现/确证、及新药开发。本实验室建立了与上述疾病发病密切相关的肝细胞、巨噬细胞、肝星状细胞的细胞及疾病动物研究平台，针对在病理情况下上述各种细胞发生紊乱的代谢通路（如自噬溶酶体，代谢重编程等）及细胞间/组织间发生紊乱的通讯(Cross talk)开展新机制的研究、新靶点发现和小分子/核酸及细胞治疗创新药物的开发。

使用手段：各种疾病模型小鼠/转基因小鼠、多种基因递送载体、CRISPR-Cas9技术、类器官、代谢组/转录组/蛋白质组学技术。

1.首次发现肝脏羧酸酯酶CES1, CES2参与非酒精性脂肪肝病致病机理，是新颖的肝脏甘油三酯水解酶，可以作为MASLD的治疗靶点。研究成果以第一作者发表于肝病领域权威杂志Hepatology, 2014: 59:1761-1771与Hepatology, 2016:63:1860-1874; 发表文章被当期Hepatology杂志高度评价，得到Faculty1000 Prime 推荐。

2.首次发现了动脉粥样硬化的新的致病通路: FOXA3-ApoAI, ATF3-p53-SRB1及ATF3-HNF4a-CYP8B1等，阐明此两条通路通过调节逆向胆固醇转运和肠道胆固醇吸收跨器官调节血液胆固醇水平影响动脉粥样硬化发病的机制。相关成果以第一作者发表在代谢领域权威杂志Nature Metabolism, 2021, 3(1):59-74与动脉粥样硬化领域专业杂志Arteriosclerosis, Thrombosis, and Vascular Biology, 2019, 39(8):1574-1587。

3.参与开发了多个新颖的治疗代谢性疾病的小分子。

· 糖尿病候选新药开发：参与开发的AMPK 激活剂项目与Roche罗氏中国研发中心合作，已进行系统临床前研究；参与开发的DPPIV抑制剂项目已经拿到临床批件，实现成果转化；相关成果以共同第一作者发表在ACS Med. Chem. Lett.等4篇药物化学及药理学专业杂志及申请国内国际专利。

· MASH候选新药开发：与美国Intercept公司合作开发，相关成果以第一作者发表于Hepatology。

· 肝纤维化新药开发：参与Ionis公司反义核酸开发，以主持人身份获得美国NIH基金支持。

代表性论著（*：最后通讯/共同通讯作者；#: 第一/共同第一作者）

[1] Yaxin Sun, Xiaoyan Yuan, Zhenhua Hu*, Yuanyuan Li*. Harnessing nuclear receptors to modulate hepatic stellate cell activation for liver fibrosis resolution. Biochemical Pharmacology，2025，232: 116730.

[2] Zhenhua Hu, Xiao Xiao, Guiyun Zhang, Yuanyuan Li*. Revolutionizing fixed-dose combinations with long-acting microsphere. European Journal of Pharmaceutical Sciences， 2025: 207: 107032.

[3] Ting Huang, Chenqi Bei, Zhenhua Hu*, Yuanyuan Li*, CAR-macrophage: Breaking new ground in cellular immunotherapy. Frontiers in Cell and Developmental Biology，2024，12: 1464218.

[4] Xiao Xiao, Feiyu Yang, Yuling Huang, Shaohui Liu, Zhenhua Hu, Shanggao Liao*, Yuanyuan Li*, Enhanced In Vitro Efficacy of Verbascoside in Suppressing Hepatic Stellate Cell Activation via ROS Scavenging with Reverse Microemulsion. Antioxidants (Basel). 2024，13(8): 907.

[5] Ying Li#, Zhenhua Hu#, Yuanyuan Li*, Xiaoyan Wu* Charting new paradigms for CAR-T cell therapy beyond current Achilles heels. Front Immunol, 2024，15:1409021.

[6] Xiaoyan Yuan, Junting Yang, Yuling Huang, Jia Li*, Yuanyuan Li*, Gut Microbiota Metabolite 3-Indolepropionic Acid Directly Activates Hepatic Stellate Cells by ROS/JNK/p38 Signaling Pathways. Biomolecules，2023， 13(10): 1464.

[7] Yanyong Xu#, Yuanyuan Li#, Kavita Jadhav#, Xiaoli Pan, Yingdong Zhu, Shuwei Hu,  Shaoru Chen, Liuying Chen, Yong Tang, Helen H Wang, Ling Yang, David Q-H Wang, Liya Yin, Yanqiao Zhang. Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism. Nature Metabolism, 2021, 3(1):59-74

[8] Yuanyuan Li#, Yanyong Xu#, Kavita Jadhav, Liya Yin and Yanqiao Zhang. Hepatic forkhead box protein A3 regulates ApoA I expression, cholesterol efflux and atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 2019, 39(8):1574-1587

[9] Yuanyuan Li, Munaf Zalzala, Kavita Jadhav, Yang Xu, Takhar Kasumov, Liya Yin and Yanqiao Zhang. Carboxylesterase 2 Prevents Liver Steatosis by Modulating Lipolysis, ER stress and Lipogenesis and is regulated by Hepatocyte Nuclear Factor 4 Alpha in Mice. Hepatology, 2016, 63(6):1860-1874 此研究内容获得美国肝病研究协会（AASLD）2016年学术年会杰出海报奖

[10] Jiesi Xu #, Yuanyuan Li #, Wei Dong Chen #, Yang Xu #, Liya Yin, Xuemei Ge, Kavita Jadhav, Luciano Adorini, and Yanqiao Zhang. Hepatic Carboxylesterase 1 Is Essential for Both Normal and Farnesoid X Receptor Controlled Lipid Homeostasis. Hepatology, 2014, 59(5):1761-1771被同期Hepatology 高度评价，Faculty of 1000 推荐

[11] Yuanyuan Li, Kavita Jadhav, and Yanqiao Zhang. Bile acid receptors in non-alcoholic fatty liver disease. Biochemical Pharmacology, 2013, 86(11):1517-24

[12] Yuan-Yuan Li#, Li-Fang Yu#, Li-Na Zhang, Bei-Ying Qiu, Ming-Bo Su, Fang Wu, Tao Pang, Min Gu, Wei Zhang, Da-Kai Chen,Wei-Ping Ma, Jing-Ya Li*, Fa-Jun Nan*, Jia Li*. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice. Toxicology and Applied Pharmacology, 2013, 273(2):325-34

[13] Li-Fang Yu#, Yuan-Yuan Li#, Ming-Bo Su, Mei Zhang , Wei Zhang , Li-Na Zhang , Tao Pang , Run-Tao Zhang , Bing Liu , Jing-Ya Li*, Jia Li*, and Fa-Jun Nan*. Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators. ACS Med. Chem. Lett., 2013, 4 (5): 475–480

[14] Linrong Zhu#, Yuanyuan Li#, Qiu Ling, Mingbo Su, Xin Wang, Chunmei Xia, Yi Qu, Jingya Li, Jia Li*, Bin Xiong*, Jingkang Shen*. Design and Synthesis of 4-(2,4,5-Trifluorophenyl)butane-1,3-diamines as Dipeptidyl Peptidase IV Inhibitors. ChemMedChem, 2013, 8(7):1104-16

[15] Zhang Liu#, Qian Chai#, Yuanyuan Li#, Qiang Shen, Lanping Ma*, Lina Zhang, Xin Wang, Li Sheng, Jingya Li, Jia Li*, Jingkang Shen. Discovery of novel PTP1B inhibitors with antihyperglycemic activity. Acta Pharmacologica Sinica, 2010, 31(8):1005–1012

[16] Yanyong Xu#, Xiaoli Pan#, Shuwei Hu#, Yingdong Zhu, Fathima Cassim Bawa, Yuanyuan Li, Liya Yin, Yanqiao Zhang. Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice. Am J Physiol Gastrointest Liver Physiol，2021，320(2):G166-G174

[17] Yanyong Xu, Yingdong Zhu, Kavita Jadhav, Yuanyuan Li, Huihui Sun, Liya Yin, Takhar Kasumov, Xiaoli Chen, Yanqiao Zhang. Lipocalin-2 Protects Against Diet-Induced Nonalcoholic Fatty Liver Disease by Targeting Hepatocytes. Hepatology Communications, 2019, 3(6):763-775

[18] Kavita Jadhav#, Yang Xu#, Yanyong Xu#, Yuanyuan Li, Jiesi Xu, Yingdong Zhu, Luciano Adorini, Yoon Kwang Lee, Takhar Kasumov, Liya Yin, Yanqiao Zhang. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Molecular Metabolism, 2018, 9:131-140

[19] Jiesi Xu, Yang Xu, Yuanyuan Li, Kavita Jadhav, Min You, Liya Yin & Yanqiao Zhang (2016). Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury. Scientific Reports, 2016, 6:24277

[20] Michael L. Multhaup, Marcus M. Seldin, Andrew E. Jaffe, Xia Lei, Henriette Kirchner, Prosenjit Mondal, Yuanyuan Li, Varenka Rodriguez, Alexander Drong, Mehboob Hussain, Cecilia Lindgren, Mark McCarthy, Erik Naslund, Juleen R. Zierath, G. William Wong, Andrew P. Feinberg. Mouse-Human Experimental Epigenetic Analysis Unmasks Dietary Targets and Genetic Liability for Diabetic Phenotypes. Cell Metabolism, 2015, 21(1):138-49 得到 Nature Reviews Endocrinology杂志高度评价

[21] Yang Xu#, Munaf Zalzala#, Jiesi Xu, Yuanyuan Li, Liya Yin, Yanqiao Zhang. A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism. Nature communications, 2015, 6:7466

[22] Prosenjit Mondal#, Woo-Jin Song#, Yuanyuan Li, Kil S. Yang, and Mehboob A. Hussain. Increasing β-Cell Mass Requires Additional Stimulation for Adaptation to Secretory Demand. Mol Endocrinol., 2015, 29(1):108-20

[23] Ryan C. Riddle, Julie M. Leslie, Mathieu Ferron, Yuanyuan Li, Douglas J.Digirolamo, Marie-Claude Faugere, Mehboob A. Hussain, Gerard Karsenty and Thomas L. Clemens. Tsc2 Is a Molecular Checkpoint Controlling Osteoblast Development and Glucose Homeostasis. Molecular and Cellular Biology, 2014:34(10):1850-62

[24] Jiesi Xu, Liya Yin, Yang Xu, Yuanyuan Li, Munaf Zalzala, Gang Cheng, Yanqiao Zhang. Hepatic Carboxylesterase 1 Is Induced by Glucose and Regulates Postprandial Glucose Levels. PLoS ONE, 2014, 9(10):e109663

[25] Woo-Jin Song#, Prosenjit Mondal#, Yuanyuan Li, Suh Eun Lee and Mehboob A. Hussain. Pancreatic β-cell Response to Increased Metabolic Demand and to Pharmacologic Secretagogues Requires EPAC2A. Diabetes, 2013, 62(8):2796-807 得到同期Diabetes杂志高度评价

[26] Li-Na Zhang, Hua-Yong Zhou, Yan-Yun Fu, Yuan-Yuan Li, Fang Wu, Min Gu, Ling-Yan Wu, Chun-Mei Xia, Tian-Cheng Dong, Jing-Ya Li*, Jing-Kang Shen*, and Jia Li*. Novel Small-Molecule PGC-1α Transcriptional Regulator With Beneficial Effects on Diabetic db/db Mice. Diabetes, 2013, 62(4):1297-307

[27] Li-Na Zhang, Lei Xu, Hua-Yong Zhou, Ling-Yan Wu, Yuan-Yuan Li, Tao Pang, Chun-Mei Xia, Bei-Ying Qiu, Min Gu, Tian-Cheng Dong, Jing-Ya Li*, Jing-Kang Shen*, Jia Li*. Novel Small-Molecule AMP-Activated Protein Kinase Allosteric Activator with Beneficial Effects in db/db Mice. PLoS ONE, 2013, 8(8):e72092

[28] Beiying Qiu, Turner N, Yuanyuan Li, Ming Gu, Mingwei Huang, Fang Wu, Tao Pang, Fajun Nan, Jiming Ye, Jingya Li*, Jia Li*. High-Throughput Assay for Modulators of Mitochondrial Membrane Potential Identifies a Novel Compound With Beneficial Effects on db/db Mice. Diabetes, 2010, 59(1):256–265

[29] Zhe Cheng#, Anfeng Chen#, Fang Wu, Li Sheng, Hankun Zhang, Min Gu, Yuanyuan Li, Lina Zhang, Lihong Hu*, Jingya Li*, Jia Li*. 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Bioorganic & Medicinal Chemistry, 2010, 18(16):5915–5924

[30] Guanghui Deng, Deju Ye, Yuanyuan Li, Lingyan He, Yu Zhou, Jiang Wang, Jia Li, Hualiang Jiang, Hong Liu. Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl) propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers. Tetrahedron, 2008, 64(46):10512-10516

[31] Xiang Guang-ya, Liang Rong-bei, Li Yan-ping, Li Yuanyuan. Synthesis of NO-releasing oxaprozin and determination of NO-releasing activities in vitro. Central South Pharmacy, 2005, 3(4):206