研究方向
? 免疫系統(tǒng)中重要SLC轉(zhuǎn)運(yùn)蛋白對(duì)免疫細(xì)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(yùn)蛋白對(duì)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(jī)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(yùn)蛋白對(duì)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(yīng)用。
科學(xué)貢獻(xiàn)
陳立功博士主要研究重要轉(zhuǎn)運(yùn)蛋白的生理和藥理功能，首次發(fā)現(xiàn)了多種轉(zhuǎn)運(yùn)蛋白的內(nèi)源性底物以及他們?cè)诿庖摺⑸窠?jīng)系統(tǒng)和代謝性疾病中的致病機(jī)理以及潛在的藥物靶點(diǎn)，2019年分別發(fā)現(xiàn)神經(jīng)外單胺轉(zhuǎn)運(yùn)蛋白SLC22A3調(diào)節(jié)白色脂肪組織米色化進(jìn)而影響機(jī)體產(chǎn)熱和腦部智力和認(rèn)知發(fā)育重要轉(zhuǎn)運(yùn)蛋白SLC6A8調(diào)節(jié)肌酸轉(zhuǎn)運(yùn)影響巨噬細(xì)胞極化和免疫反應(yīng)；2018年分別發(fā)現(xiàn)氨基酸轉(zhuǎn)運(yùn)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(xué)院合作提出人工智能和機(jī)器學(xué)習(xí)預(yù)測(cè)藥物靶點(diǎn)；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(guān)注和引用，多次受到Science, Scientific American和F1000作為研究亮點(diǎn)進(jìn)行報(bào)道；在博士期間，闡述了離子通道GABAA受體拮抗劑的結(jié)構(gòu)和功能活性關(guān)系，提出“多樣性結(jié)構(gòu)拮抗劑結(jié)合同一位點(diǎn)”的假說，獲得PNAS高度評(píng)價(jià)和特別報(bào)道。近年來先后擔(dān)任了國(guó)家重大新藥創(chuàng)制、國(guó)家重大研發(fā)計(jì)劃、國(guó)家重大研究計(jì)劃和比爾蓋茨基金會(huì)重大項(xiàng)目等多個(gè)項(xiàng)目的負(fù)責(zé)人。并兼任中國(guó)藥理學(xué)會(huì)腎臟藥理分會(huì)常委，中國(guó)生物物理學(xué)會(huì)代謝生物學(xué)分會(huì)理事，北京市藥物代謝學(xué)會(huì)副主委、北京市藥物化學(xué)生物學(xué)會(huì)副主委等。在國(guó)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(yùn)蛋白對(duì)免疫系統(tǒng)的調(diào)控和藥物開發(fā)
? 針對(duì)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(yàn)證，人源化的小鼠脂肪肝和原位肝癌模型
? SLC轉(zhuǎn)運(yùn)蛋白對(duì)神經(jīng)系統(tǒng)疾病包括老年癡呆癥，多發(fā)性結(jié)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(jié)構(gòu)和功能關(guān)系研究
榮譽(yù)和獎(jiǎng)勵(lì)
1. 中國(guó)科協(xié)“中華英才”十周年杰出導(dǎo)師獎(jiǎng)（2024）
2. 清華大學(xué)書院本科生培養(yǎng)杰出導(dǎo)師獎(jiǎng)（2023）
3. 清華大學(xué)綜合治理獎(jiǎng)（2023）
4. 中國(guó)科協(xié)“中華英才”杰出導(dǎo)師獎(jiǎng)（2023）
5. 清華大學(xué)先進(jìn)工作者（2023）
6. 北京市杰出本科生論文指導(dǎo)導(dǎo)師獎(jiǎng)（2023）
7. 北京市杰出本科生論文指導(dǎo)導(dǎo)師獎(jiǎng)（2021）
8. 清華大學(xué)杰出研究生導(dǎo)師獎(jiǎng)（2021）
9. 清華大學(xué)藥學(xué)院優(yōu)秀教學(xué)獎(jiǎng)（2020）
10. 北京市杰出本科生論文指導(dǎo)導(dǎo)師獎(jiǎng)（2019）
11. 清華大學(xué)杰出導(dǎo)師獎(jiǎng)（2019）
12. 清華大學(xué)藥學(xué)院公共服務(wù)卓越獎(jiǎng)（2019）
13. 國(guó)家“萬人計(jì)劃”中青年科技創(chuàng)新領(lǐng)軍人才（2019）
14. 清華大學(xué)優(yōu)秀教學(xué)獎(jiǎng)（2018）
15. 藥明康德生命化學(xué)獎(jiǎng)（2017）
16. 拜耳研究員獎(jiǎng)（2015-2018）
17. 楊森研究者獎(jiǎng)（2014-2015）
18. 海外高層次人才計(jì)劃青年項(xiàng)目（2013年）
19. 輝瑞治療創(chuàng)新獎(jiǎng)（2011）
20. 加州大學(xué)舊金山分校QB3全球生物企業(yè)家獎(jiǎng)學(xué)金
21. 加州大學(xué)舊金山分校旅行獎(jiǎng)（2009）
22. 加州大學(xué)伯克利分校董事獎(jiǎng)學(xué)金（2001-2004）
23. 南開大學(xué)的各種獎(jiǎng)學(xué)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.
