Research | Ligong ChEN, Ph.D.

Ligong ChEN

Principal Investigator

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 principal investigator 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.


Research Interests

Molecular Pharmacology and Physiology of SLC Transporters: Studies of important drugs and drug targets in metabolic diseases and cancer, and further small molecules or biologics drug development. A) Physiological and pharmacological roles of SLC transporter in GWAS leading to differences in drug reactions or significant disease risk factor. The main approaches apply OMICs and mouse models systematically studying their unknown endogenous substrate and molecular pathways, thereby identifying new drug targets and new therapeutic approaches; B) Personalized medicine studying the gene polymorphism in different races, different efficacy of the drug in the individuals to establish a more effective treatment and pharmacogenomics testing standards.
Systems and Molecular Toxicology: Studying representative drugs toxicity on liver, kidneys and immune system.
Protein engineering studies drug and target interactions: Structure-Based Drug Discovery will utilize the protein structure simulation, massive compound libraries screening with computational biology and pharmacological functional verification. From above findings of our group, we will focus on translating them to drug discovery or secondary development of the established drugs or biomarkers.

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.   Tang H, Wang X, Xu L, Ran X, Li X, Chen L, Zhao X, Deng H, Liu X. Establishment of local searching methods for orbitrap-based high throughput metabolomics analysis. Talanta. 2016,156-157:163-71.
2.   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 Chem Biol. 2016. [Epub ahead of print]. ACS Chem Biol. (*Co-corresponding).
3.   Zhang S, Zhou J, Hu H, Gong H, Chen L, Cheng C, Zeng J. 2015. A deep learning framework for modeling hierarchical structural specificities and predicting binding sites of RNA-binding proteins. Nucleic Acids Res. 2016, 44(4):e32.
4.   Wang H, Wang S, Cheng L, Chen L, Wang Y, Qing J, Huang S, Wang Y, Lei X, Wu Y, Ma Z, Zhang L, Tang Y. 2015. Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor. ACS Med Chem Lett. 6:977-81.
5.   Chen EC, Liang X, Yee SW, Stocker SL, Geier EG, Chen L, Giacomini KM. 2015. Targeted Disruption of Organic Cation Transporter 3 (Oct3) Attenuates the Pharmacologic Response to Metformin. Mol Pharmacol. 88:75-83.
6.  Liang Y, Li S, Chen L* 2015. The Physiological role of drug transporters. Protein Cell. 6:334-50. (*Corresponding).
7.  Chen L, Yee SW, Giacomini KM. 2015. The drug transporter physiologically important. Cell Cycle. 14:283-284.
8.  Chen L, Shu Y, Liang X, et al. 2014. OCT1 is a high capacity thiamine transporter regulating hepatic steatosis and is a target of metformin. Proc Natl Acad Sci U S A. 111: 9983-8.
9.  Chen L, Hong C, Chen EC, et al. 2013. Genetic and Epigenetic Regulation of the Organic Cation Transporter 3, SLC22A3. Pharmacogenomics J. 13:110-20.
10.  Yee SW#, Chen L#, Giacomini KM. 2012. The role of ATM in response to metformin treatment and activation of AMPK. Nat Genet. 44:359-60. (# Co-first authors)
11.  Chen L, Xue L, Giacomini KM, John E. Casida. 2011. GABAA receptor open-state conformation determines non-competitive antagonist binding. Toxicol Appl Pharmacol. 250: 221-8.
12.  Chen L, Pawlikowski B, Schlessinger A, et al. 2010. Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenet Genomics. 20: 687-99.
13.  Chen L, Takizawa M, Chen E, et al. 2010. Genetic polymorphisms in organic cation transporter 1 (OCT1) in Chinese and Japanese populations exhibit altered function. J Pharmacol Exp Ther. 335:42-50.
14.  Chen L, Durkin K, Casida JE. 2006. Spontaneous mobility of GABAA receptor M2 extracellular half relative to noncompetitive antagonist action. J Biol Chem. 281: 38871-8.
15.  Chen L, Durkin K, Casida JE. 2006. Structural model for GABA receptor noncompetitiveantagonist binding: widely-diverse structures fit the same site. Proc Natl Acad Sci U S A. 103: 5185-10.
16.  Ahlin G, Chen L, LazorovaL, et al. 2011. Genotype dependent effects of inhibitors of the organic cation transporter, OCT1:  Predictions of metformin interactions. Pharmacogenomics J. 11: 400-11.
17.  Yee SW, Chen L, Giacomini KM. 2010. Pharmacogenomics of drug transporters: past, present and future. Pharmacogenomics. 11: 475-9.
18.  More SS, Li S, Yee SW, Chen L, et al. 2010. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third generation platinum analog. Mol Cancer Ther. 9: 1058-69.
19.  Andrews-Zwilling Y, Bien-Ly N, Xu Q, Li G, Bernardo A, Yoon SY, Zwilling D, Yan Chen L, and Huang Y. 2010. Apolipoprotein E4 causes Tau-dependent hilar GABAergic interneuron impairment, leading to learning and memory deficits in mice. J Neurosci. 30: 13707-17.
20.  Hesselson SE, Matsson P, Shima JE, Fukushima H, Yee SW, Kobayashi Y, Gow JM, Ha C, Ma B, Poon A, Johns SJ, Stryke D, Castro RA, Tahara H, Choi JH, Chen L, et al. 2008. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation. PLoS One. 4: e6942
21.  Chen Y, Li S, Brown C, Cheatham S, Castro RA, Leabman MK, Urban TJ, Chen L, et al. 2009. Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics. 19: 497-504.
Huang SM, Chen L, Giaocmini KM, Pharmacogenomic Mechanism of Drug Toxicity. The Principle of Clinical Pharmacology (3rd edition), Chapter 17. 
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)