Personal HistoryDr. de Leeuw received his Ph.D. in Molecular Biochemistry from the Free University of Amsterdam, the Netherlands. He further trained as a Research Associate at the University of East Anglia, United Kingdom and Oxford University, United Kingdom. In 2005, Dr. de Leeuw joined the Instiute of Human Virology where he currently holds the position of Assistant Professor.
Research InterestsResearch Overview
The innate immune system has evolved as an ancient defense system against infection. Effectors of innate immunity include a variety of innate immune cells as well as antimicrobial peptides (AMPs). Antimicrobial peptides are ancient components of the innate immunity. These molecules interact with and rapidly inactivate infectious agents by a mechanism which is generally mediated by disruption of the integrity of the microbial membranes. In mammals, AMPs are synthesized and secreted in those tissues that are exposed to environmental microbes, such as skin and mucosal epithelia, where they provide an immediate-early defense against infection. Accumulating evidence indicates that AMPs act not only as innate microbicidal agents, but can mediate a range of other biological effects, such as modulation of transcriptional responses in host cells, chemotaxis of inflammatory and immune cells, re-epithelization of healing skin, induction of angiogenesis and apoptosis of transformed and immune cells, thereby linking the innate to the adaptive immune system. Dr. de Leeuw's main interest is the molecular characterization of the biological activities of host defense peptides to evaluate their potential as novel anti-infective drugs.
Selected Recent Publications
Wei, G., de Leeuw, E., Pazgier, M., Yuan, W., Zou, G., Wang, J., Ericksen, B., Lu, W.Y., Lehrer, R.I. and Lu, W. (2009) Through the looking glass: Mechanistic insights from enantiomeric human defensins. J. Biol. Chem. e-published ahead of print
De Leeuw, E., Rajabi, M., Zou, G., Pazgier, M. and Lu, W. (2009) Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5. FEBS Letters 583(15), 2507-2512
Zou, G., De Leeuw, E., Lubkowski, J. and Lu, W. (2008) Molecular determinants for the interaction of Human Neutrophil alpha defensin 1 with its propeptide. J. Mol. Biol. 381, 1281-1291
Rajabi, M., De Leeuw, E., Pazgier, M., Li, J., Lubkowski, J. and Lu, W. (2008) The conserved salt-bridge in Human alpha-Defensin 5 is required for its precursor processing and proteolytic stability. J. Biol. Chem. 283, 21509-21518
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 non-coded analogs. J. Biol. Chem. 282, 19653-19665
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 alpha-Defensins. J. Mol. Biol. 368, 537-549
De Leeuw, E. and Lu, W. (2007) Human Defensins: Turning Defense into Offense? Infectious Disorders: Drug Targets 7(1), 67-70
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 Letters 581(3), 515-520
De Leeuw, E., Li, X., and Lu, W. (2006) Binding characteristics of the Lactobacillus brevis S-layer to Extra Cellular Matrix proteins. FEMS Microbiology Letters, 260, 210-215
Wu, Z., Li, X., De Leeuw, E., Ericksen, B. and Lu, W. (2005) Why is the Arg5-Glu13 salt bridge conserved in mammalian ï¡-defensins? (2005) J. Biol. Chem. 280, 43039-43047
Li X, De Leeuw E. and Lu W. Total chemical synthesis of human psoriasin by native chemical ligation. (2005) Biochemistry 44, 14688-14694
Gohlke U, Pullan L, McDevitt CA, Porcelli I, De Leeuw E. Palmer T, Saibil, HR and Berks BC The TatA component of the twin-arginine protein transport system forms channel complexes of variable diameter (2005) PNAS 102, 10482-10486