Cell Signal Transduction and Innovative Drug Discovery Laboratory
 | Mingyao Liu |
| Dean, School of Life Sciences | |
| Director, Institute of Biomedical Sciences and Shanghai Key Laboratory of Regulatory Biology | |
| Distinguished National Endowed Professor | |
| Professor, Texas A&M University Health Science Center |
Curriculum Vitae
Dr. Mingyao Liu received his Ph.D. Degree in Cell Biology from the University of Maryland, College Park in 1992. From 1993-1998, he did his postdoctoral trainings in Johns Hopkins University School of Medicine and California Institute of Technology (Caltech) with Prof. King-Wai Yau and Melvin I Simon, respectively. In 1999, he was recruited to the Institute of Biosciences and Technology, Texas A&M University as an assistant professor, then promoted to associated professor in 2003 and full professor with tenure in 2007. In 2007, Dr. Liu was recruited as the director of the Institute of Biomedical Sciences, then appointed as the dean of School of Life Sciences and the director of Shanghai Key Laboratory of Regulatory Biology, East China Normal University in 2012. Together with his colleagues, Dr. Liu established the laboratory for cell signaling and innovative drug discovery. In 2008, he was selected as the Distinguished Endowed Professor by “The Recruitment Program of Global Experts”.
Achievements in Scientific Research
Dr. Liu’s lab has been focused on the study of G-protein coupled receptors and their signaling pathways, especially orphan GPCRs and their biological functions. He has published more than 120 articles on leading scientific journals, including Science, Nature, PNAS, Cell, JNCI, Cancer Research, etc. His papers have been cited for more than 4000 times.
Dr. Liu’s lab was supported by the National Natural Science Foundation, the Ministry of Science and Technology, the “973” national program, and many other research fundings.
Research Interests
1、GPCRs, the most successful targets for modern medicine, play essential roles in a variety of physiological functions. Our basic research interests have centered on an understanding of the physiological functions of GPCRs (including orphan receptors) through the studies on knockout mouse models, and eventually to identify and characterize potential drug targets.
2、Through cell-based assay targeting GPCRs and tumor-specific signaling transduction, we screened several chemical libraries (FDA approved drug library, novel-structure library, natural products library and GPCR targeted library) and found multiple lead compounds with effective inhibition on tumor growth and metastasis. We next pursue to understand and validate the precise target of these compounds on the platforms of cell signaling transduction and bioinformatics.
3、Based on our preliminary work as well as signaling and structure information of metabolic -related GPCRs (such as GLP1R, TGR5, GPR55, GPR119, fatty acid receptor GPR40, 41,43 and GPR120, etc.), we used the molecular docking model assay to screen a virtual compounds library targeting these GPCRs. A library of small molecules based on virtual screening was collected via organic synthesis, and then the biological activity screening was verified against signaling pathway or targets to get hit compounds, which was further designed, modified and optimized for gaining lead compound through medicinal chemistry, combinatorial chemistry technologies, and computer-aided design. The lead compound will then be evaluated for its effect in preclinical studies.
4、Starting from hit or natural bioactive compounds obtained from specific target-oriented screening, the hit compounds were further rationally designed, synthesized and modification for systemic studies on structure-activity relationship, which would result in the discovery of lead compounds. We want to screen for DMPK properties, including absorption, metabolic pathways, metabolite stability, and drug-drug interactions via drug metabolic enzymes. At the same time, both in vitro and animal in vivo studies are done in the preclinical stage. Most promising compounds are selected from in vitro studies and their pharmacokinetic parameters are obtained in two animal species.
Selected Publications:
1. Cho SG, Wang Y, Rodriguez M, Tan K, Li D, and Liu M. Kiss1 G protein-coupled receptor (Gpr54) haploinsufficiency delays breast tumor initiation, progression and lung metastasis. Cancer Research 2011; 71(20)6535-46.
2. Li D, Qiu Z, Shao Y, Chen Y, Guan Y, Liu M, Li Y, Gao N, Wang L, Lu X, Zhao Y and Liu M. Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nature Biotechnology. 2013; 31:681-3.
3. Wang J, Liu R, Wang F, Hong J, Li X, Chen M, Ke Y, Zhang X, Ma Q, Wang R, Shi J, Cui B, Gu W, Zhang Y, Zhang Z, Wang W, Xia X, Liu M, Ning G. Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch.Nat Cell Biol. 2013; 15(12):1455-63.
4. Fang Y, Chen Y, Yu L, Zheng C, Qi Y, Li Z, Yang Z, Zhang Y, Shi T, Luo J, Liu M. Inhibition of Breast Cancer Metastases by a Novel Inhibitor of TGF beta Receptor 1. JNCI. 2013; 105:47-58.
5. Tang X, Jin R, Qu G, Wang X, Li Z, Yuan Z, Zhao C, Siwko S, Shi T, Wang P, Xiao J, Liu M, Luo J. GPR116, an Adhesion G-Protein-Coupled Receptor, Promotes Breast Cancer Metastasis via the Gaq-p63RhoGEF-Rho GTPase Pathway. Cancer Research. 2013; 73: 6206-18.
6. Wang Y, Dong J, Li D, Lai L, Siwko S, Li Y, Liu M. Lgr4 Regulates Mammary Gland Development and Stem Cell Activity Through the Pluripotency Transcription Factor Sox2. Stem Cells. 2013; 31:1921-31.
7. Li L, Gao N, Zhao Y, Li X, Lu Y, Liu M, Li D. 2013. Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is essential for spermatogenesis. Development. 2013; 140:1751-61.
8. Qiu Z, Liu M, Chen Z, Shao Y, Pan H, Wei G, Yu C, Zhang L, Li X, Wang P, Fan HY, Du B, Liu B, Liu M, Li D. High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases.Nucleic Acids Res. 2013; 41(11):e120.
9. Du B, Luo W, Li R, Tan B, Han H, Lu X, Li D, Qian M, Zhang D, Zhao Y, Liu M. Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression.J Biol Chem. 2013; 288(21):15131-41.
10. Cui H, Wang Y, Huang H, Yu W, Bai M, Zhang L, Bryan BA, Wang Y, Luo J, Li D, Ma Y, Liu M. 2014. GPR126 protein regulates developmental and pathological angiogenesis through modulation of VEGFR2 receptor signaling.J Biol Chem. 2014; 289(50):34871-85.
11. Guan X, Duan Y, Zeng Q, Pan H, Qian Y, Li D, Cao X, Liu M. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.J Biol Chem. 2014; 289(38):26492-504.
12. Yang F, Zhang T, Wu H, Yang Y, Liu N, Chen A, Li Q, Li J, Qin L, Jiang B, Wang X, Pang X, Yi Z, Liu M, Chen Y. 2014. Design and optimization of novel hydroxamate-based histone deacetylase inhibitors of Bis-substituted aromatic amides bearing potent activities against tumor growth and metastasis. J Med Chem. 2014; 57(22):9357-69.
13. Yi T, Weng J, Siwko S, Luo J, Li D, Liu M.LGR4/GPR48 inactivation leads to aniridia-genitourinary anomalies-mental retardation syndrome defects. J Biol Chem. 2014; 289(13):8767-80.
14. Guan Y, Shao Y, Li D, Liu M. 2014. Generation of site-specific mutations in the rat genome via CRISPR/Cas9.Methods Enzymol. 2014; 546:297-317.
15. Shao Y, Guan Y, Wang L, Qiu Z, Liu M, Chen Y, Wu L, Li Y, Ma X, Liu M, Li D. Genome editing in the rat using CRISPR-Cas and injection of RNAs into one-cell embryos. Nature Protocols. 2014; 9(10): 2493-2512.