研究方向
? 免疫系統(tǒng)中重要SLC轉(zhuǎn)運蛋白對免疫細胞極化、分化及抗體產(chǎn)生的影響及免疫調(diào)節(jié)藥物的開發(fā)；
? 神經(jīng)系統(tǒng)中重要SLC轉(zhuǎn)運蛋白對神經(jīng)元再生、髓鞘再生和神經(jīng)遞質(zhì)的穩(wěn)態(tài)調(diào)控機制及神經(jīng)疾病的潛在治療策略；
? 肝臟、脂肪中重要SLC轉(zhuǎn)運蛋白對代謝穩(wěn)態(tài)調(diào)控及在脂肪肝、肝癌和代謝性疾病中的應用。
科學貢獻
陳立功博士主要研究重要轉(zhuǎn)運蛋白的生理和藥理功能，首次發(fā)現(xiàn)了多種轉(zhuǎn)運蛋白的內(nèi)源性底物以及他們在免疫、神經(jīng)系統(tǒng)和代謝性疾病中的致病機理以及潛在的藥物靶點，2019年分別發(fā)現(xiàn)神經(jīng)外單胺轉(zhuǎn)運蛋白SLC22A3調(diào)節(jié)白色脂肪組織米色化進而影響機體產(chǎn)熱和腦部智力和認知發(fā)育重要轉(zhuǎn)運蛋白SLC6A8調(diào)節(jié)肌酸轉(zhuǎn)運影響巨噬細胞極化和免疫反應；2018年分別發(fā)現(xiàn)氨基酸轉(zhuǎn)運蛋白和脂代謝通路在肝癌中的重要功能和潛在治療途徑；2017年與交叉信息學院合作提出人工智能和機器學習預測藥物靶點；2014年提出抑制OCT1治療脂肪肝新型策略。這些工作均引起廣泛關注和引用，多次受到Science, Scientific American和F1000作為研究亮點進行報道；在博士期間，闡述了離子通道GABAA受體拮抗劑的結構和功能活性關系，提出“多樣性結構拮抗劑結合同一位點”的假說，獲得PNAS高度評價和特別報道。近年來先后擔任了國家重大新藥創(chuàng)制、國家重大研發(fā)計劃、國家重大研究計劃和比爾蓋茨基金會重大項目等多個項目的負責人。并兼任中國藥理學會腎臟藥理分會常委，中國生物物理學會代謝生物學分會理事，北京市藥物代謝學會副主委、北京市藥物化學生物學會副主委等。在國際著名期刊Nature Genetics、Immunity、Gut、Hepatology、Nature Communications, PLOS Biology 和 PNAS等發(fā)表高水平論文近60篇。
研究成果
? SLC轉(zhuǎn)運蛋白對免疫系統(tǒng)的調(diào)控和藥物開發(fā)
? 針對脂肪肝和肝癌開發(fā)治療性單體克隆抗體和基因療法，包括生物活性驗證，人源化的小鼠脂肪肝和原位肝癌模型
? SLC轉(zhuǎn)運蛋白對神經(jīng)系統(tǒng)疾病包括老年癡呆癥，多發(fā)性結節(jié)硬化癥和癲痢等疾病的調(diào)節(jié)和潛在的治療方法開發(fā)
? SLC結構和功能關系研究
榮譽和獎勵
1. 中國科協(xié)“中華英才”十周年杰出導師獎（2024）
2. 清華大學書院本科生培養(yǎng)杰出導師獎（2023）
3. 清華大學綜合治理獎（2023）
4. 中國科協(xié)“中華英才”杰出導師獎（2023）
5. 清華大學先進工作者（2023）
6. 北京市杰出本科生論文指導導師獎（2023）
7. 北京市杰出本科生論文指導導師獎（2021）
8. 清華大學杰出研究生導師獎（2021）
9. 清華大學藥學院優(yōu)秀教學獎（2020）
10. 北京市杰出本科生論文指導導師獎（2019）
11. 清華大學杰出導師獎（2019）
12. 清華大學藥學院公共服務卓越獎（2019）
13. 國家“萬人計劃”中青年科技創(chuàng)新領軍人才（2019）
14. 清華大學優(yōu)秀教學獎（2018）
15. 藥明康德生命化學獎（2017）
16. 拜耳研究員獎（2015-2018）
17. 楊森研究者獎（2014-2015）
18. 海外高層次人才計劃青年項目（2013年）
19. 輝瑞治療創(chuàng)新獎（2011）
20. 加州大學舊金山分校QB3全球生物企業(yè)家獎學金
21. 加州大學舊金山分校旅行獎（2009）
22. 加州大學伯克利分校董事獎學金（2001-2004）
23. 南開大學的各種獎學金（1993-1997）
代表性論文
1. Zhang S, Zhu A, Kong F, et al, Yan C*, Chen L*, Liu X*. Structure insight into human organic cation transporter 1 transport and inhibition. Cell Discovery, 2024, 10(1):30.
2. Chi W#, Kang N#, Sheng L#, Liu S#, et al Liu W*, Chen L*. MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation. Nature Communications, 2024,15(1):163.
3. Cheng L, et al Fan H*, Chen L*. Hepatic mitochondrial NAD+ transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis, Hepatology, 2023, 78(6):1828-1842.
4. Xu B#, Zhang M#, Zhang B#, Chi W#, Ma X, Zhang W, Dong M, Sheng L, Zhang Y, Jiao W, Shan Y, Chang W, Wang P, Wen S, Pei D, Chen L*, Zhang X*, Yan H*, Ye S*. Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state. Cell Reports, 2022, 40(11): 111343.
5. Chi W, Zhang Y, Yang J, Chen L*. CD147 complex: a putative early predictive biomarker for preeclampsia? Clinical and Translational Discovery. 2022, 2: e76.
6. Zhao J, Wang Y, Tao L, Chen L*. Iron Transporters and Ferroptosis in Malignant Brain Tumors. Frontier Oncology. 2022, 12: 861834.
7. Liu Y#, Chi W#, Tao L, Wang G, Deepak RNVK, Sheng L, Chen T, Feng Y, Cao X, Cheng L, Zhao X, Liu X, Deng H, Fan H, Jiang P, Chen L*. Ablation of H+/glucose Exporter SLC45A2 Enhances Melanosomal Glycolysis to Inhibit Melanin Biosynthesis and Promote Melanoma Metastasis. J Investigative Dermatology. 2022, 142(10): 2744-2755.
8. Sheng L#, Luo Q#, Chen L*. Amino Acid Solute Carrier Transporters in Inflammation and Autoimmunity. Drug Metabolism and Disposition. 2022,50 (9): 1228-1237.
9. Chen R, Chen L*. Solute Carrier Transporters: Emerging Central Players in Tumour Immunotherapy. Trends in Cell Biology. 2022, 32(3): 186-201.
10. Feng Y, Tao L, Wang G, Li Z, Yang M, He W, Zhong X, Zhang Y, Yang J, Cheung S*, McDonald F*, Chen L*. Aspirin inhibits prostaglandins to prevents colon tumor formation via down-regulating Wnt production. European Journal of Pharmacology, 2021, 906: 174173
11. Kuang W, Zhang J, Lan Z, Deepak RNVK, Liu C, Ma Z, Cheng L, Zhao X, Meng X, Wang W, Wang X, Xu L, Jiao Y, Luo Q, Meng Z, Kee K, Liu X, Deng H, Li W, Fan H, Chen L*. SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility. Cell Reports. 2021, 35(3):109025.
12. Liu Q, Sun Z*, Chen L*. Memory T cells: strategies for optimizing tumor immunotherapy. Protein & Cell, 2020, 2020, 11(8): 549-564.
13. Hu C, Tao L, Cao X, Chen L*. The solute carrier transporters and the brain: physiological and pharmacological implications. Asian Journal of Pharmaceutical Sciences, 2020,15(2), 131-144 (Cover Story).
14. Song W#, Li D#, Tao L, Luo Q, Chen L*. Solute carrier transporters: the metabolic gatekeepers of immune cells. Acta Pharmaceutica Sinica B, 2020, 10(1), 61-78.
15. Che L, Chi W, Qiao Y, Liu Y, Li L, Jia J, Wang J, Cigliano A, Ma Z, Kuang W, Tang Z, Zhang Z, Shui G, Ribback S, Dombrowski F, Osborne TF, Pilo MG, Calvisi DF*, Chen X*, Chen L*. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut, 2020, 69 (1), 177-186.
16. Chen L*, Chen X-W*, Huang X*, Wang Y*, Wang Y*, Song B-L*. Regulation of glucose and lipid metabolism in health and disease, SCIENCE CHINA Life Sciences, 2019, 62 (11), 1420-1458.
17. Ji L#, Zhao X#, Zhang B, Kang L, Song W, Zhao B, Xie W, Chen L*, Hu X*. Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses. Immunity, 2019, 51,1-13.
18. Song W#, Luo Q#, Zhang Y, Zhou L, Liu Y, Ma Z, Guo J, Huang Y, Cheng L, Meng Z, Li Z, Zhang B, Li S, Yee SW, Fan H, Li P, Giacomini KM*, Chen L*. Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue. PLOS Biology, 2019,17(1): e2006571. (Highlighted with Press Release “Blocking hormone uptake burns more fat”; Featured Article with Commentary “Fat cells gobbling up norepinephrine”).
19. Zhang Y#, Zhang Y#, Sun K, Meng Z, Chen L*. The SLC transporter in nutrient and metabolic sensing, regulation, and drug development. Journal of Molecular Cell Biology, 2019, 11(1): 1-13. (Featured Article).
20. Li C#, Chen H#, Lan Z, He S, Chen R, Wang F, Liu Z, Li K, Cheng L, Liu Y, Sun K, Wan X, Chen X, Peng H, Li L, Zhang Y, Jing Y, Huang M, Wang Y, Wang Y, Jiang J, Zha X, Chen L*, Zhang H*. mTOR-dependent upregulation of xCT blocks melanin synthesis and promotes tumorigenesis. Cell Death & Differentiation, 2019, 26 (10), 2015-2028.
21. Wang X#, Gao H#, Wu W, Xie E, Yu Y, He X, Li J, Zheng W, Wang X, Cao X, Meng Z, Chen L*, Min J*, Wang F*. The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α?mediated regulation of Glut2. Protein & Cell, 2019, 10: 436-449.
22. Cheng L#, Ge M#, Lan Z#, Ma Z, Chi W, Kuang W, Sun K, Zhao X, Liu Y, Feng Y, Huang Y, Luo M, Li L, Zhang B, Hu X, Xu L, Liu X, Huo Y, Deng H, Yang J, Xi Q, Zhang Y, Siegenthaler JA, Chen L*. Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Archives of Toxicology (Top Journal in toxicology), 2018, 92(1): 469-485.
23. Liu P#, Ge M #, Hu J#, Li X#, Che L#, Sun K, Cheng L, Huang Y, Pilo MG, Cigliano A, Pes GM, Pascale RM, Brozzetti S, Vidili G, Porcu A, Cossu A, Palmieri G, Sini MC, Ribback S, Dombrowski F, Tao J, Calvisi DF*, Chen L*, Chen X*. A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis. Hepatology, 2017, 66(1): 167-181.
24. Luo Y#, Zhao X#, Zhou J#, Yang J, Zhang Y, Kuang W, Peng J *, Chen L*, Zeng J *. A network integration approach for drug-target interaction prediction and computational drug repositioning from heterogeneous information. Nature Communications, 2017, 8(1): 573. (Editor’s choice as featured Article).
25. Zhao X, Sun K, Lan Z, Song W, Cheng L, Chi W, Chen J, Huo Y, Xu L, Liu X, Deng H, Siegenthaler JA, Chen L*. Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity. Scientific Reports, 2017, 7: 46344.
26. Ung PM#, Song W#, Cheng L, Zhao X, Hu H, Chen L*, Schlessinger A*. Inhibitor discovery for the human GLUT1 from homology modeling and virtual screening. ACS Chemical Biology, 2016, 11(7): 1908-1916.
