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Wuyuan Lu
Ph.D.
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| Academic Title:
Professor |
| Primary Appointment:
Biochemistry and Molecular Biology |
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wlu@ihv.umaryland.edu |
| Location:
MRF, 725 W. Lombard St.,
S-516 |
| Phone:
(410) 706-4980 |
| Fax:
(410) 706-7583 |
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Personal History
EDUCATION
• 1980-1984: B.S., Department of Chemistry, Nanjing University, China
• 1987-1989: M.S., Department of Biochemistry, Nanjing University, China
• 1990-1994: Ph.D., Department of Chemistry, Purdue University
• 1995-1996: Postdoctoral Fellow, Department of Cell Biology, the Scripps Research Institute
• 1998-2000: Research Associate (Asistant Professor), Department of Biochemistry and Molecular Biology, the University of Chicago
PROFESSIONAL EXPERIENCE
• 1984-1987: Research Assistant, Institute of Dermatology, Chinese Academy of Medical Sciences, China
• 1997-1998: Senior Staff Scientist and Research Group Leader, Gryphon Sciences, Inc., San Francisco
• 2000-2005: Assistant Professor, Institute of Human Virology, University of Maryland Biotechnology Institute
• 2005-2007: Associate Professor, Institute of Human Virology, University of Maryland Biotechnology Institute
• 2005-Present: Member, University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine
• 2007-Present: Member, Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine
• 2007-2009: Associate Professor, Department of Biochemistry & Molecular Biology and Institute of Human Virology, University of Maryland School of Medicine
• 2009-present: Professor, Department of Biochemistry & Molecular Biology and Institute of Human Virology, University of Maryland School of Medicine
Research Interests
• HIV-1 Assembly and Maturation
• Activation of the Tumor Suppressor Protein p53
• Chemical Protein Engineering via Native Chemical Ligation
• Structure and Function Relationships for Proteins in Innate Host Defense
Publications
Wu, Z., Powell, R. and Lu, W. (2003). Productive folding of human neutrophil α-defensins in vitro without the pro-peptide. J. Am. Chem. Soc. 125, 2402-2403.
Wu, Z., Hoover, D.M., Yang, D., Boulegue, C., Santamaria, F., Oppenheim, J., Lubkowski, J. and Lu, W. (2003). Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc. Natl. Acad. Sci. USA 100, 8880-8885.
Wu, Z., Alexandratos, J., Ericksen, B., Lubkowski, J., Gallo, R.C. and Lu, W. (2004). Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation. Proc. Natl. Acad. Sci. USA 101, 11587-11592.
Ericksen, B., Wu, Z., Lu, W. and Lehrer, R.I. (2005). Bactericidal activities and specificities of all six synthetic human α-defensins. Antimicrob. Agents Chemother. 49, 269-275.
Wu, Z., Cocchi, F., Gentles, D., Ericksen, B., Lubkowski, J., DeVico, A., Lehrer, R.I. and Lu, W. (2005). Human neutrophil α-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 579, 162-166.
Xie, C., Prahl, A., Ericksen, B., Wu, Z., Zeng, P., Li, X., Lu, W-Y., Lubkowski, J., and Lu, W. (2005). Reconstruction of the conserved beta-bulge in mammalian defensins using D-amino acids. J. Biol. Chem. 280, 32921-32929.
John, M., Keller, M.J., Fam, E.H., Cheshenko, N., Hogarty, K., Kasowitz, A., Wallenstein, S., Carlucci, M.J., Tuyama, A.C., Lu, W., Lehrer, R.I., Klotman, M.E., and Herold, B.C. (2005). Cervicovaginal secretions contribute to innate resistance to HSV infection. J. Infect. Dis. 192, 1731-40.
Economopoulou, M., Bdeir, K., Cines, D.B., Fogt, F., Bdeir, Y., Lubkowski, J., Lu, W., Preissner, K.T., Hammes, H-P., and Chavakis, T. (2005). Inhibition of pathological retinal neovascularization by α-defensins. Blood 106, 3831-8.
Sun, L., Finnegan, C., Kish-Catalone, T., Blumenthal, R., Garzino-Demo, P., La Terra Maggiore, G.M., Berrone, S., Kleinman, C., Wu, Z., Abdelwahab, S., Lu, W., and Garzino-Demo, A. (2005). Human beta-defensins suppress HIV infection: potential role in mucosal protection. J. Virol. 79, 14318-29.
Li, X., de Leeuw, E., and Lu, W. (2005). Total chemical synthesis of human psoriasin by native chemical ligation. Biochemistry 44, 14688-94.
Wu, Z., Li, X., de Leeuw, E., Ericksen, B., and Lu, W. (2005). Why is the Arg5-Glu13 salt bridge conserved in mammalian α-defensins? J. Biol. Chem. 280, 43039-43047.
Buck, C.B., Day, P.M., Thompson, C.D., Lubkowski, J., Lu, W., Lowy, D.R., and Schiller J.T. (2006). Human alpha-defensins block papillomavirus infection. Proc. Natl. Acad. Sci. USA 103, 1516-21.
Kish-Catalone, T.M., Lu, W., Gallo, R.C., and DeVico, A.L. (2006). Preclinical evaluation of synthetic 2 RANTES as a candidate vaginal microbicide to target CCR5. Antimicrob. Agents Chemother. 50, 1497-509.
Wang, W., Mulakala, C., Ward, S.C., Jung, G., Luong, H., Pham, D., Waring, A.J., Kaznessis, Y., Lu, W., Bradley, K.A., and Lehrer, R.I. (2006). Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin. J. Biol. Chem. 281(43):32755-64.
Lim, J.K., Lu, W., Hartley, O., and DeVico, A.L. (2006). N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related analogs into a truncated 4-68 variant. J. Leukoc. Biol. 80(6):1395-404.
Szyk, A., Wu, Z., Tucker, K., Yang, D., Lu, W., and Lubkowski, J. (2006). Crystal structures of human α-defensins HNP4, HD5, and HD6. Protein Sci. 15(12):2749-60.
Hazrati, E., Galen, B., Lu, W., Wang, W., Ouyang, Y., Keller, M.J., Lehrer, R.I., and Herold, B.C. (2006). Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J. Immunol. 177, 8658-66.
Li, X., Zou, G., Yuan, W., and Lu, W. (2007). Defining the native disulfide topology in the somatomedin B domain of human vitronectin. J. Biol. Chem. 282(8):5318-26.
De Leeuw, E., Burks, S.R., Li, X., Kao, J.P.Y., and Lu, W. (2007). Structure-dependent functional properties of human defensin 5. FEBS Lett. 581(3):515-520.
Wu, Z., Li, X., Ericksen, B., De Leeuw, E., Zou, G., Zeng, P., Xie, C., Li, C., Lubkowski, J., Lu, W-Y., and Lu, W. (2007). Impact of pro segments on the folding and function of human neutrophil α-defensins. J. Mol. Biol. 368(2):537-549.
Zou, G., de Leeuw, E., Li, C., Pazgier, M., Li, C., Zeng, P., Lu, W.-Y., Lubkowski, J., and Lu, W. (2007). Toward understanding the cationicity of defensins: Arg and Lys versus their noncoded analogs. J. Biol. Chem. 282(27):19653-65.
Shi, J., Aono, S., Lu, W., Ouellette, A.J., Hu, X., Ji, Y., Wilson, C., Parks, W., Wang, L., Lenz, S., Dykstra, C., Morrison, E.E., and Elson, C.O. (2007). A novel role for defensins in intestinal homeostasis: regulation of IL-1 beta secretion. J. Immunol. 179(2):1245-53.
Saad, J.S., Kim, A., Ghanam, R.H., Dalton, A.K., Vogt, V.M., Wu, Z., Lu, W., and Summers, M.F. (2007). Mutations that mimic phosphorylation of the HIV-1 matrix protein do not perturb the myristyl switch. Protein Sci. 16(8):1793-7.
Klotman, M.E., Rapista, A., Teleshova, N., Micsenyi, A., Jarvis, G.A., Lu, W., Porter, E., and Chang, T.L. (2008). Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission. J. Immunol. 180(9):6176-85.
Rajabi, M., de Leeuw, E., Pazgier, M., Li, J., Lubkowski, J., and Lu, W. (2008). The conserved salt bridge in human a-defensin 5 is required for its precursor processing and proteolytic stability. J. Biol. Chem. 283(31):21509-18 (selected as a Paper of the Week).
Li, C., Wu, Z., Liu, M., Pazgier, M., and Lu, W. (2008). Chemically synthesized human survivin does not inhibit caspase-3. Protein Sci. 17(9):1624-9.
Zou, G., de Leeuw, E., Lubkowski, J., and Lu, W. (2008). Molecular determinants for the interaction of human neutrophil a-defensin 1 with its pro peptide. J. Mol. Biol. 381(5):1281-91.
Li, C., Liu, M., Monbo, J., Zou, G., Li, C., Yuan, W., Zella, D., Lu, W-Y., and Lu, W. (2008). Turning a scorpion toxin into an antitumor miniprotein. J. Am. Chem. Soc. 130(41):13546-13548.
Gryllos, I., Cheng, M-F., Chung, H., Bolcome, R., Lu, W., Lehrer, R.I., and Wessels, M.R. (2008). Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl. Acad. Sci. USA 105(43):16755-60.
Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S.G., and Lu, W. (2009). Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX. Proc. Natl. Acad. Sci. USA 106(12):4665-70.
Lehrer RI, Jung G, Ruchala P, Andre S, Gabius HJ, Lu W (2009). Multivalent binding of carbohydrates by the human α-defensin HD5. J. Immunol. 183(1):480-490.
Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Compopiano DJ, Gray M (2009). Dying and necrotic neutrophils are anti-inflammatory secondary to the release of α-defensins. J. Immunol. 183(3):2122-32.
de Leeuw E, Rajabi M, Zou G, Pazgier M, Lu W (2009). Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5. FEBS Lett. 583(15):2507-12.
Lehrer RI, Jung G, Ruchala P, Wang W, Micewicz ED, Waring AJ, Gillespie EJ, Bradley KA, Ratner AJ, Rest RF, Lu W (2009). Human α-defensins inhibit hemolysis mediated by cholesterol-dependent cytolysins. Infect. Immun. 77(9):4028-40.
Wei G, de Leeuw E, Pazgier M, Yuan W, Zou G, Wang J, Ericksen B, Lu W-Y, Lehrer RI, Lu W (2009). Through the looking glass: mechanistic insights from enantiomeric human defensins. J. Biol. Chem. July 29 (Epub ahead of print).
Li C, Pazgier M, Liu M, Lu W-Y, Lu W (2009). Apamin as a novel template for structure-based rational design of potent peptide activators of p53. Angew. Chem. Int. Ed. (in press).
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