• 免疫系统中重要SLC转运蛋白对免疫细胞极化、分化及抗体产生的影响及免疫调节药物的开发；
• 神经系统中重要SLC转运蛋白对神经元再生、髓鞘再生和神经递质的稳态调控机制及神经疾病的潜在治疗策略；
• 肝脏、脂肪中重要SLC转运蛋白对代谢稳态调控及在脂肪肝、肝癌和代谢性疾病中的应用。

 

陈立功博士主要研究重要转运蛋白的生理和药理功能，首次发现了多种转运蛋白的内源性底物以及他们在免疫、神经系统和代谢性疾病中的致病机理以及潜在的药物靶点，2019年分别发现神经外单胺转运蛋白SLC22A3调节白色脂肪组织米色化进而影响机体产热和脑部智力和认知发育重要转运蛋白SLC6A8调节肌酸转运影响巨噬细胞极化和免疫反应；2018年分别发现氨基酸转运蛋白和脂代谢通路在肝癌中的重要功能和潜在治疗途径；2017年与交叉信息学院合作提出人工智能和机器学习预测药物靶点；2014年提出抑制OCT1治疗脂肪肝新型策略。这些工作均引起广泛关注和引用，多次受到Science, Scientific American和F1000作为研究亮点进行报道；在博士期间，阐述了离子通道GABAA受体拮抗剂的结构和功能活性关系，提出“多样性结构拮抗剂结合同一位点”的假说，获得PNAS高度评价和特别报道。近年来先后担任了国家重大新药创制、国家重大研发计划、国家重大研究计划和比尔盖茨基金会重大项目等多个项目的负责人。并兼任中国药理学会肾脏药理分会常委，中国生物物理学会代谢生物学分会理事，北京市药物代谢学会副主委、北京市药物化员工物学会副主委等。在国际著名期刊Nature Genetics、Immunity、Gut、Hepatology、Nature Communications, PLOS Biology 和 PNAS等发表高水平论文近60篇。

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研究成果

•  SLC转运蛋白对免疫系统的调控和药物开发

•  针对脂肪肝和肝癌开发治疗性单体克隆抗体和基因疗法，包括生物活性验证，人源化的小鼠脂肪肝和原位肝癌模型

•  SLC转运蛋白对神经系统疾病包括老年痴呆症，多发性结节硬化症和癫痢等疾病的调节和潜在的治疗方法开发

•  SLC结构和功能关系研究

  

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荣誉和奖励

1. Excellent instructor for Innovative Student Development, Tsinghua University (2022)

2. Outstanding Undergraduate Mentor Award of Beijing (2021)

3. Outstanding Graduate Mentor Award, Tsinghua University (2021)

4. Outstanding Teaching Award of SPS, Tsinghua University (2020)

5. Outstanding Undergraduate Mentor Award, Beijing (2019)

6. Outstanding Mentor Award, Tsinghua University (2019)

7. Excellence in Public Service Award in SPS,  Tsinghua University (2019)

8. National Leading Talents in Science and Technology Innovation (2019)

9. Excellence In Teaching Award of Tsinghua University (2018)

10. WuXi AppTec Prize for Chemical Biology and Pharmacology (2017)

11. Outstanding Mentor of Research Science Initiative (2016-2017)

12. Bayer Young Investigator Award (2015-2018)

13. Janssen Young Investigator Award (2014-2015)

14. National 1000-Talent Program in China (2013)

15. Regents Fellowship, UC Berkeley (2001-2004)
    

1. Zhao J, Wang Y, Tao L, Chen L*. Iron Transporters and Ferroptosis in Malignant Brain Tumors. Front Oncol. doi: 10.3389/fonc.2022.861834. eCollection 2022.
2. 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 Invest Dermatol. 2022, 142(10):2744-2755.e9.
3. Sheng L#, Luo Q#, Chen L*. Amino Acid Solute Carrier Transporters in Inflammation and Autoimmunity. Drug Metab Dispos. 2022, 50 (9) 1228-1237 (Featured Article).
4. Chen R, Chen L*. Solute Carrier Transporters: Emerging Central Players in Tumour Immunotherapy. Trends in Cell Biology, 2022, 32(3):186-201.
5. 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.
6. 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.
7. Liu Q, Sun Z*, Chen L*. Memory T cells: strategies for optimizing tumor immunotherapy. Protein & Cell, 2020, 2020, 11(8): 549-564.
8. 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).
9. 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 (Editor Award).
10. 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 (Highly cited paper).
11. 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.
12. 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.
13. 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”).
14. 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).
15. 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.
16. 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.
17. 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 toxicological science), 2018, 92(1): 469-485. (Most downloaded article last 6 months).
18. 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.
19. 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).
20. 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