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Wu's Laboratory

Donghai Wu, Ph.D.
Principal Investigator

Dr.Wu, received his B. Sc. in Biology from Beijing Normal University, China in 1984. He was then enrolled in the CUSBMEA program and went to University of Texas Southwestern Medical Center at Dallas where he obtained his Ph. D. in Biochemistry and Molecular Biology. Dr. Wu held faculty positions in the Department of Biochemistry, College of Medicine of University of Kentucky and the Department of Medicinal Chemistry, College of Pharmacy of University of Florida before he joined Guangzhou Institutes of Biomedicine and Health, Chinese Academy and Sciences in 2004. The major research interests and the long-term goal of his work are to understand the underlying molecular mechanisms of metabolic disorders such as diabetes and obesity, and to develop innovative biomedical strategies to promote the prevention, diagnosis and treatment of theses diseases. Dr. Wu has published more than 60 papers and held five patents.


(1) Molecular mechanism of obesity related metabolic disorders.
Obesity accelerates aging and is a major risk factor for a panel of metabolic related disorders including insulin resistance, cardiovascular diseases, and diabetes. A better understanding of the molecular mechanism how these metabolic disorders result from the onset of obesity would greatly benefit the prevention and treatment of the diseases and attain healthy aging. A series of metabolism related animal models (genetically engineered mice and large animal models) have been established in our lab. Specifically, by using the tissue specific gene knockout mice, we are able to dissect the role of a certain gene in the pathogenesis of metabolic diseases and aging under the circumstances of obesity. In addition, study on the transgenic/knockout animal models facilitates the validation of drug targets.

(2) Stem cell biology and application in regenerative medicine.
Induced pluripotent stem (iPS) cells represent an invaluable tool for regenerative medicine. We sought to contribute to the iPS cell technologies by working on the following two aspects: 1) To differentiate iPS cell to defined lineages with either transcription factors or culture conditions; 2) To apply the iPS technology to treatment of diseases and screen novel drugs.

(3) Large scale expression and production of commercially valuable proteins.
Bioactive proteins are used in a wide spectrum of the biomedicine field, raging from basic researches, cosmetics to disease treatment. The production of biologically active proteins in large quantity is often challenging but rewarding as well. We adopt several expression systems to realize the large scale production of biologically active proteins important for stem cell research.

1. Y.Wang, J.B. Lam, K.S.L. Lam, J. Liu, M.C. Lam, R.L.C. Hoo, D.Wu, G.J.S. Cooper, and A. Xu (2006) Adiponectin Modulates the Glycogen Synthase Kinase-3B/B-Catenin Signaling Pathway and Attenuates Mammary Tumorigenesis of MDA-MB-231 Cells in Nude Mice. Cancer Res. 66(23): 11462 - 11470.
2. K.K. Y. Cheng, K. S. L .Lam, Y.Wang, C. David, H.Yu,D.Wu, C. Wong, , and A.Xu (2007) Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells Diabetes. 56(5):1387-94.
3. Y. Gao, Y.Zhou, A.Xu and D.Wu (2008) Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells Biol. Pharm. Bull. 31(9);1716-22.
4. Y.Yang, Y.Wang, K. S. L .Lam, M. Yau, K.K. Y. Cheng, J. Zhang, W. Zhu, D.Wu and A.Xu (2008) Suppression of the Raf/MEK/ERK Signaling Cascade and Inhibition of Angiogenesis by the Carboxyl Terminus of Angiopoietin-like Protein 4 ATVB. 28(5):835-40.
5. A.Xu, H.Wang, R.Hoo, P.Vanhoutte, Y.Wang, D.Wu, W.Chu, G.Qin and K. S. L .Lam (2009) Selective Elevation of Adiponectin Production by the Natural Compounds Derived from a Medicinal Herb Alleviates Insulin Resistance and Glucose Intolerance in Obese Mice Endocrinology. 150(2):625-33.
6. Y.Luo, X.Kong, A.Xu, S. Jin and D. Wu (2009) Expression, purification and characterization of human recombinant interleukin 7. Protein Expression and Purification 63:1-4.
7. X,Gao, W.Chen, X.Kong, A,Xu,Z.Wang,G.Sweeney and D.Wu (2009) Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake Diabetologia 52(5):912-20.
8. M. Yau, Y.Wang, K.S.L. Lam, J. Zhang, D. Wu and A. Xu (2009) A highly conserved motif within the NH2-terminal coiled-coil domain of angiopoietin-like protein 4 confers its inhibitory effects on lipoprotein lipase through disrupting the enzyme dimerization J. Biol. Chem. 284: 11942 – 11952.
9. Y.Zhou, D.Wang, Q.Zhu, X. Gao, A.Xu and D.Wu (2009) Inhibitory effects of a novel AMP-activated protein kinase activator, A769662, on adipogenic differentiation of 3T3-L1 cells Biol. Pharm. Bull. Jun; 32(6):993-8.
10. H. Li, D. Wang, A. Xu, S. Li, S. Jin and D. Wu (2009) High level expression and purification of active recombinant human interleukin-8 in Pichia pastoris Protein Expression and Purification 68:60-4.
11. X. Hui, W. Zhu, Y.Wang, K.S.L. Lam, J. Zhang, D. Wu, E. Kraegen, Y. Li and A. Xu (2009) Major Urinary Protein-1 Increases Energy Expenditure And Improves Glucose Intolerance Through Enhancing Mitochondrial Function In Skeletal Muscle of Diabetic Mice J. Biol. Chem. 284: 14050 - 14057.
12. X. Hui, Y. Li, Z. Zhou, K.S.L. Lam, Y.Xiao, D.Wu, K.Ding,Y.Wang P.M.Vanhoutte and A. Xu (2010) Adipocyte fatty acid binding protein mediates inflammatory response in macrophages through a positive feedback loop involving c-Jun N-terminal kinases and activator protein-1 J. Biol. Chem. 285(14):10273-80.
13. W. Lian, D. Wu, D.V. Lim and S. Jin (2010) Sensitive Detection of Multiplex Toxins Using Antibody Microarray Anal. Biochem. 401(2):271-9 .
14. L. Wen, J. Liu, Y. Chen and D. Wu (2010) Identification and preliminary functional analysis of alternative splicing of Siah1 in Xenopus laevis BBRC. 396(2):419-24.
15. L. Wen, Y. Yang, Y. Wang, A. Xu, D. Wu and Y. Chen (2010) Appl1 is Essential for the Survival of Xenopus Pancreas, Duodenum, and Stomach Progenitor Cells Developmental Dynamics. 239(8):2198-207.
16. M. Zhou, A. Xu, K. S. L. Lam, P. K. H. Tam, C. Che, L. Chan, I. Lee, D. Wu and Y. Wang (2010) Rosiglitazone promotes fatty acyl CoA accumulation and excessive glycogen storage in livers of mice without adiponectin J. Hepatol. 53(6):1108-16.
17. H. Li, Y. Wang, A. Xu, S. Li, S. Jin and D. Wu (2010) Large-scale production, purification and bioactivity assay of recombinant human interleukin-6 in the methylotrophic yeast Pichia pastoris FEMS. 11(2):160-7.
18. X. Ren, L. Duan, Q. He, Z. Zhang, Y. Zhou, D. Wu, J. Pan, D. Pei and K. Ding (2010) Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway Med Chem. Lett. In press.
19. C. Bichsel, D.K.Neeld, T. Hamazaki, D. Wu, L. Chang, L. Yang, N. Terada and S. Jin (2011) Bacterial Delivery of Nuclear Proteins into Pluripotent and Differentiated Cells PLOSone. 6(1):e16465.
20. X. Gao, K. Li, X. Hui, X. Kong, G. Sweeney, Y. Wang, A. Xu, M. Teng, P. Liu and D. Wu (2011) Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocytes dysfunction through suppression of c-Jun N-terminal kinase Biochem.J. 435(3):723-32.
21. M. Park, B. Youn, X. Zheng, D.Wu, A.Xu, and G.Sweeney (2011) Adiponectin prevents hypoxia/reoxygenation-induced apoptosis in cardiomyocytes via AdipoR1/APPL1 signaling PLOSone. In press.
22. X. Liu, X. Huang, W. Lin, D. Wang, Y. Diao, H. Li, X. Hui, Y. Wang, A. Xu, D. Wu and K. Ding (2011) New Aromatic Substituted Pyrazoles as Selective Inhibitors of Human Adipocyte Fatty Acid-Binding Protein Bioorganic & Med Chem. Lett. In press. DOI 10.1016/j.bmcl. 2011.03.063.
23. H. Li, X. Gao, Y. Zhou, N. Li, C. Ge, X. Hui, Y. Wang, A. Xu, S. Jin and D. Wu (2011) High level expression, purification and characterization of active fusion human C1q and tumor necrosis factor related protein 2 (hCTRP2) in Escherichia coli Protein Expression and Purification In press. 10.1016/j.pep.2011.03.013.
24. S. Gao, G. Zhu, X. Gao, D. Wu, P. Carrasco, N. Casals, FG. Hegardt, TH. Moran and GD. Lopaschuk. (2011) Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding PNAS In press.
25. Y. Wang, K.Y. Cheng, K.S.L. Lam, D. Wu, Y. Wang, Y. Huang, P.M. Vanhoutte, G. Sweeney, Y. Li and A. Xu. (2011) APPL1 Counteracts Obesity-induced Vascular Insulin Resistance and Endothelial Dysfunction by Fine-tuning the Endothelial Production of Nitric Oxide and Endothelin-1 in Mice Diabetes In press.
26. H. Li, X. Gao, N. Li, S. Li, X. Kong, A. Xu, S. Jin and D. Wu (2011) High level expression, purification and characterization of active recombinant human interleukin-3 in Pichia pastoris Protein Expression and Purification In press.


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