Faculty |
Ligong CHEN, Ph.D.

Ligong CHEN, Professor

Dr. Ligong Chen obtained his BS from Nankai University in Chemistry in 1997. He completed his PhD from University of California at Berkeley and postdoctoral training from UCSF in 2006 and 2011, respectively. Currently, he is a Professor in pharmacology and toxicology of School of Pharmaceutical Science at Tsinghua University. His research areas include transporter pharmacology and toxicology. His lab is working on various transporters' role in human diseases and molecular mechanism of drug toxicity.


Professional Experience

Dr. Ligong Chen obtained his BS from Nankai University in Chemistry in 1997. He completed his PhD from University of California at Berkeley and postdoctoral training from UCSF in 2006 and 2011, respectively. Currently, He is tenured professor in pharmacology and toxicology in School of Pharmaceutical Science at Tsinghua University. His research area is the SLC transporter physiology and pharmacology. His lab is working on various transporters‘ roles in human diseases and molecular mechanism of drug toxicity. Using advanced molecular and genomic approaches with cell and animal models, Dr. Chen has discovered several important transporters’ physiological substrates and their functions in fatty liver, cancer, neurological disorders and immunity. He has published more than 50 publications including those on Nature Genetics, Immunity, Gut, Hepatology, Nature Communications, PNAS and Cell Reports et al. He has been selected to national 1000 talent program and national leading scientists in innovation and technology and won many awards like the Wuxi Apptec Chemical Biology Award and Excellence in Teaching and of Tsinghua University.

Research Interests

· The impact of important SLC transporters on the immune system for the polarization, differentiation and antibody production of immune cells for the development of immunomodulatory drugs;            
· Mechanisms of neuronal regeneration, remyelination and neurotransmitter homeostasis regulation by important SLC transporters in the nervous system for potential therapeutic strategies for neurological diseases;           
· Regulation of metabolic homeostasis by important SLC transporters in liver and adipose tissue with their application in fatty liver, liver cancer and metabolic diseases.          
           

Scientific Contributions 

Dr. Chen Ligong primarily focuses on the physiological and pharmacological functions of important transporter proteins. He has made groundbreaking discoveries in identifying endogenous substrates of various transporter proteins and elucidating their pathogenic mechanisms in immune, neurological, and metabolic diseases, as well as their potential as drug targets. In 2019, he discovered that the neuronal monoamine transporter SLC22A3 regulates beige adipocyte differentiation in white adipose tissue, thereby affecting thermogenesis, and that the crucial transporter SLC6A8 for brain intellectual and cognitive development regulates creatine transport, impacting macrophage polarization and immune responses. In 2018, he uncovered the significant functions of amino acid transporter proteins and lipid metabolism pathways in liver cancer, as well as potential therapeutic approaches. In 2017, in collaboration with the School of Interdisciplinary Information Science and Technology, he proposed the use of artificial intelligence and machine learning to predict drug targets. In 2014, he introduced a novel strategy for treating fatty liver disease by inhibiting OCT1. These achievements have garnered widespread attention and citations, and have been featured in Science, Scientific American, and F1000 multiple times. During his doctoral studies, he elucidated the structure-activity relationships of GABAA receptor antagonists and proposed the hypothesis of "diverse antagonists binding to the same site," which was highly evaluated and specially reported in PNAS. In recent years, he has served as the principal investigator for several major national projects, including the National Major Scientific and Technological Special Project for "Significant New Drugs Development," the National Key Research and Development Program, the National Major Research Plan, and major projects funded by the Bill & Melinda Gates Foundation. He also concurrently holds positions such as Standing Committee Member of the Renal Pharmacology Branch of the Chinese Pharmacological Society, Council Member of the Metabolic Biology Branch of the Chinese Biophysical Society, Vice Chairman of the Beijing Society for Drug Metabolism, and Vice Chairman of the Beijing Society for Medicinal Chemistry and Biology. He has published nearly 60 high-impact papers in prestigious international journals such as Nature Genetics, Immunity, Gut, Hepatology, Nature Communications, PLOS Biology, and Cell Reports.


Selected Achievements

• Regulation of the Immune System by SLC Transporter Proteins and Drug Development


• Development of Therapeutic Monoclonal Antibodies and Gene Therapies for Fatty Liver Disease and Hepatocellular Carcinoma, Including Bioactivity Validation and Humanized Mouse Models of Fatty Liver Disease and Orthotopic Hepatocellular Carcinoma


• Modulation of Neurological Diseases by SLC Transporter Proteins, Including Alzheimer's Disease, Multiple Sclerosis, and Epilepsy, and Development of Potential Therapeutic Approaches


• Research on the Structure-Function Relationship of SLC Transporter Proteins


Honors and Awards

1. Outstanding Mentor Award of Chinese “High School Talent Plan” of 10-Year Anniversary (2024)

2. Outstanding Mentor Award of Undergraduate Training, Tsinghua University (2023)

3. Outstanding Staff of Tsinghua Campus Comprehensive Management (2023)

4. Outstanding Mentor Award of Chinese “High School Talent Plan” (2023)

5. Outstanding Staff Award, Tsinghua University (2023)

6. Outstanding Undergraduate Mentor Award of Beijing (2023)

7. Outstanding Undergraduate Mentor Award of Beijing (2021)

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

9. Excellent Teaching Award of School of Pharmaceutical Sciences, Tsinghua University (2020)

10. Outstanding Undergraduate Mentor Award, Beijing (2019)

11. Outstanding Mentor Award, Tsinghua University (2019)

12. Excellence in Public Service Award in School of Pharmaceutical Sciences, Tsinghua University (2019)

13. National Leading Talents in Science and Technology Innovation, China (2019)

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

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

16. Outstanding Mentor of Research Science Initiative, MIT-Tsinghua (2016-2017)

17. Bayer Young Investigator Award (2015-2018)

18. Janssen Young Investigator Award (2014-2015)

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

20. Pfizer Therapeutic Innovation Award (2011)

21. Scholarship for QB3 Global Bio-Entrepreneurship, UCSF (2010)

22. UCSF Travel Award (2009)

23. Department Student Award, UC Berkeley (2005)

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

25. Various Scholarships from Nankai University in China (1993-1997)


Selected Publications

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.


BOOK CHAPTER
Huang SM, Chen L, Giaocmini KM, Pharmacogenomic Mechanism of Drug Toxicity. The Principle of Clinical Pharmacology (3rd edition), Chapter 17. 

 

PATENT
Huang Y, Xu Q, Bien-Ly N, Weisgraber L, Chen L, Peters-Libeu C. Agents that Detect a Unique Conformation of ApoE and Methods of Use Thereof (U.S. Application Serial No. 61/309,280)