Xu’s Laboratory

Yong Xu, Ph.D.
Principal Investigator

Dr. Yong Xu received his Ph.D degree in Organic Chemistry from Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS) in 2004. He then joined Shanghai Institute of Organic Chemistry, CAS for his postdoctoral training in the field of computational biology and drug design. In 2006, he moved to Van Andel Research Institute and performed computational and structural biology study. Dr. Xu joined Guangzhou Institutes of Biomedicine and Health (GIBH) in 2011 as a principle investigator in the institute of chemical biology. Dr. Xu currently is the Head of Molecular Modeling and Design Laboratory in GIBH.

Personnel: 
Joint Graduate Students: Xiangyu JIN, Yu SONG, Xiaoqian XUE
Research Assistants: Zhi MA, Yan ZHANG, Jing LI

Research:
Dr. Xu’s major interest: understanding of small molecules-biological targets interaction through computational biology and structural biology; discovery and development of small molecule modulators for treating human disease, including inflammatory, tumor and metabolic diseases.

Publications:

1.	Blind RD, Pineda-Torra I, Xu Y, Xu HE, Garabedian MJ. Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy. Biochem Biophys Res Commun, 2012,420, 839-44.
2.	Cheng, H., Wang, J., Lin, M., Liu, Y., Lu, X., Liu, J., Xu, Y., Chen, J., Tu, Z., Cheng, Y., Ding, K., Design, synthesis and in vitro biological evaluation of 1H-1,2,-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein, J Med Chem, 2012, 55, 2144-53.
3.	Chang, S. , Zhang, L., Xu, S., Luo, J., Lu, X., Zhang, Z., Xu, T., Liu, Y., Tu, Z., Xu, Y., Ren, X., Geng, M., Ding, J., Pei, D., Ding, K., Design, Synthesis and Biological Evaluation of Novel Conformationally Constrained Inhibitors Targeting Epidermal Growth Factor Receptor T790M mutant. J Med Chem, 2012, 55, 2711-23.
4.	Soon, F. F., Ng, L. M., Zhou, X. E., West, G. M., Kovach, A., Tan, M. H., Suino-Powell, K. M., He, Y., Xu, Y., Chalmers, M. J., Brunzelle, J. S., Zhang, H., Yang, H., Jiang, H., Li, J., Yong, E. L., Cutler, S., Zhu, J. K., Griffin, P. R., Melcher, K., Xu, H. E. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science, 2012, 335, 85-88.
5.	Malapaka, R. R., Khoo, S., Zhang, J., Choi, J. H., Zhou, X. E., Xu, Y., Gong, Y., Li, J., Yong, E.L., Chalmers, M. J., Chang, L., Resau, J. H., Griffin, P. R., Chen, Y. E., Xu, H. E. Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors. J Biol Chem, 2012, 287, 183-195.
6.	Miao, J., Choi, S. E., Seok, S. M., Yang, L., Zuercher, W. J., Xu, Y., Willson, T. M., Xu, H. E., Kemper, J. K. Ligand-dependent regulation of the activity of the orphan nuclear receptor, small heterodimer partner (SHP), in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes. Mol Endocrinol, 2011, 25, 1159-1169.
7.	He, Y.,* Xu, Y.,* (co-first author) Zhang, C., Gao, X., Dykema, K. J., Martin, K. R., Ke, J., Hudson, E. A., Khoo, S. K., Resau, J. H., Alberts, A. S., MacKeigan, J. P., Furge, K. A., Xu, H. E. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal, 2011, 4, ra44.
8.	Xie, Q., Wondergem, R., Shen, Y., Cavey, G., Ke, J., Thompson, R., Bradley, R., Daugherty-Holtrop, J., Xu, Y., Chen, E., Omar, H., Rosen, N., Wenkert, D., Xu, H. E., Vande Woude, G. F. Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion. Proc Natl Acad Sci U S A, 2011, 108, 4105-4110.
9.	Martin, K. R., Xu, Y., Looyenga, B. D., Davis, R. J., Wu, C. L., Tremblay, M. L., Xu, H. E., MacKeigan, J. P. Identification of PTPsigma as an autophagic phosphatase. J Cell Sci, 2011, 124, 812-819.
10.	Niemi, N. M., Lanning, N. J., Klomp, J. A., Tait, S. W., Xu, Y., Dykema, K. J., Murphy, L. O., Gaither, L. A., Xu, H. E., Furge, K. A., Green, D. R., MacKeigan, J. P. MK-STYX, a catalytically inactive phosphatase regulating mitochondrially dependent apoptosis. Mol Cell Biol, 2011, 31, 1357-1368.
11.	Zhou, X. E., Suino-Powell, K. M., Xu, Y., Chan, C. W., Tanabe, O., Kruse, S. W., Reynolds, R., Engel, J. D., Xu, H. E. The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J Biol Chem, 2011, 286, 2877-2885.
12.	Melcher, K.,* Xu, Y.,* (co-first author) Ng, L. M., Zhou, X. E., Soon, F. F., Chinnusamy, V., Suino-Powell, K. M., Kovach, A., Tham, F. S., Cutler, S. R., Li, J., Yong, E. L., Zhu, J. K., Xu, H. E. Identification and mechanism of ABA receptor antagonism. Nat Struct Mol Biol, 2010, 17, 1102-1108.
13.	Powell, E., Huang, S. X., Xu, Y., Rajski, S. R., Wang, Y., Peters, N., Guo, S., Xu, H. E., Hoffmann, F. M., Shen, B., Xu, W. Identification and characterization of a novel estrogenic ligand actinopolymorphol A. Biochem Pharmacol, 2010, 80, 1221-1229.
14.	Melcher, K., Ng, L. M., Zhou, X. E., Soon, F. F., Xu, Y., Suino-Powell, K. M., Park, S. Y., Weiner, J. J., Fujii, H., Chinnusamy, V., Kovach, A., Li, J., Wang, Y., Peterson, F. C., Jensen, D. R., Yong, E. L., Volkman, B. F., Cutler, S. R., Zhu, J. K., Xu, H. E. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature, 2009, 462, 602-608.
15.	Xu, Y., Zhang, T., Chen, M. Combining 3D-QSAR, docking, molecular dynamics and MM/PBSA methods to predict binding modes for nonsteroidal selective modulator to glucocorticoid receptor. Bioorg Med Chem Lett, 2009, 19, 393-396.
16.	Kruse, S. W., Suino-Powell, K., Zhou, X. E., Kretschman, J. E., Reynolds, R., Vonrhein, C., Xu, Y., Wang, L., Tsai, S. Y., Tsai, M. J., Xu, H. E. Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. PLoS Biol, 2008, 6, e227.
17.	Tao, Y. G., Xu, Y., Xu, H. E., Simons, S. S., Jr. Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression. Biochemistry, 2008, 47, 7648-7662.
18.	Suino-Powell, K., Xu, Y., Zhang, C., Tao, Y. G., Tolbert, W. D., Simons, S. S., Jr., Xu, H. E. Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol. Mol Cell Biol, 2008, 28, 1915-1923.
19.	Guo, D., Sarkar, J., Suino-Powell, K., Xu, Y., Matsumoto, K., Jia, Y., Yu, S., Khare, S., Haldar, K., Rao, M. S., Foreman, J. E., Monga, S. P., Peters, J. M., Xu, H. E., Reddy, J. K. Induction of nuclear translocation of constitutive androstane receptor by peroxisome proliferator-activated receptor alpha synthetic ligands in mouse liver. J Biol Chem, 2007, 282, 36766-36776.
20.	Cheng, T., Zhao, Y., Li, X., Lin, F., Xu, Y., Zhang, X., Li, Y., Wang, R., Lai, L. Computation of octanol-water partition coefficients by guiding an additive model with knowledge. J Chem Inf Model, 2007, 47, 2140-2148.
21.	Wang, R., Lin, F., Xu, Y., Cheng, T. I-SOLV: a new surface-based empirical model for computing solvation free energies. J Mol Graph Model, 2007, 26, 368-377.
22.	Xu, Y., Wang, R. computational analysis of the binding affinities of FKBP12 inhibitors using the MM-PB/SA method. Proteins, 2006, 64, 1058-1068.
23.	Ma, D., Jiang, Y., Chen, F., Gong, L. K., Ding, K., Xu, Y., Wang, R., Ge, A., Ren, J., Li, J., Ye, Q. Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. J Med Chem, 2006, 49, 456-458.
24.	Niu, C., Xu, Y., Luo, X., Duan, W., Silman, I., Sussman, J. L., Zhu, W., Chen, K., Shen, J., Jiang, H. Dynamic mechanism of E2020 binding to acetylcholinesterase: a steered molecular dynamics simulation. J Phys Chem B, 2005, 109, 23730-23738.
25.	Xu, Y., Liu, H., Niu, C., Luo, C., Luo, X., Shen, J., Chen, K., Jiang, H. Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes based on the structural modeling of human CCR5 receptor. Bioorg Med Chem, 2004, 12, 6193-6208.