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 identify that thiamine (Vitamin B1) is a primary endogenous substrate of OCT1 and define its significant role in lipogenesis and glycogenesis in mouse models. Pharmacogenomics of transporters is another important aspect of our studies. He also identified and characterized the genetic variants from type 2 diabetes patients or healthy volunteer of OCT1 and OCT3, which revealed important information on the metformin pharmacogenomics. During his Ph.D. study, he discovered that structural similar GABA receptor antagonist binding at the same site.
Selected Achievements
Dentify several major drugs'molecular mechanism of adverse drug reaction relative to lipid and glucose metabolic dysfunction.
Discovering substrates and physiological function of major members of SLC22 family for potential therapeutic application in male fertility, obesity and type 2 diabetes.
Discovering the Thiamine (Vitamin B1) as the endogenous substrate of OCT1 with metabolomics and its important signal transduction role in lipogenesis and glycogenesis, metformin pharmacological action;
Identification and characterization of metformin as the substrate of OCT3 in vitro and in vivo;
Genetic and epigenetic regulation of OCT3 expression and pharmacogenomics
Established the structure-function relationship between noncompetitive antagonist (NCA) and human GABA
A receptor β3 homomer: Mapping the NCA binding site using systematic mutagenesis in transmembrane 2 of human GABAA receptor β3 homomer.
Honors and Awards
1. Bayer Investigator award (2016)
2. Janssen-Tsinghua Investigator Award (2014-2015)
3. Pfizer Therapeutic Innovation Award (2011)
4. Scholarship for QB3 Global Bio-Entrepreneurship, QB3-UCSF (2010)
5. UCSF travel award (2009)
6. Department Student Award, University of California at Berkeley (2005)
7. Regents Fellowship, University of California at Berkeley (2001-2004)
8. Scholarships from Nankai University in China (1993 - 1997)
Selected Publications
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
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)
