Biochemistry and Molecular Biology
Assistant Professor, Division of Infectious Agents and Cancer, Institute of Human Virology
725 W. Lombard Street, S413
Education and Training
1988-1995 M.S. Biochemistry, Catholic University of Nijmegen, the Netherlands
1996-2000 Ph.D. Biochemistry, Free University of Amsterdam, the Netherlands
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.
drug discovery and development; antibiotics; antivirals
Malin J1, Shetty AC2, Daugherty SC2, de Leeuw EP1.Effect of a small molecule Lipid II binder on bacterial cell wall stress. Infect Drug Resist. 2017 Feb 28;10:69-73. doi: 10.2147/IDR.S126254. eCollection 2017
Chauhan J1,2, Cardinale S3, Fang L1,4,2, Huang J1,4, Kwasny SM3, Pennington MR5, Basi K5, diTargiani R5, Capacio BR5, MacKerell AD Jr1,4, Opperman TJ3, Fletcher S1, de Leeuw EP6.Towards Development of Small Molecule Lipid II Inhibitors as Novel Antibiotics.PLoS One. 2016 Oct 24;11(10):e0164515. doi: 10.1371/journal.pone.0164515. eCollection 2016.
Zhao A, Lu W, de Leeuw E.(2015) Functional synergism of Human Defensin 5 and Human Defensin 6. Biochem Biophys Res Commun. 2015 Oct 17. pii: S0006-291X(15)30735-X. doi: 10.1016/j.bbrc.2015.10.035. [Epub ahead of print]
Fletcher S, Yu W, Huang J, Kwasny SM, Chauhan J, Opperman TJ, MacKerell AD Jr, de Leeuw E. (2015) Structure-activity exploration of a small-molecule Lipid II inhibitor. Drug Design, Development and Therapy: 9:2383-94. doi: 10.2147/DDDT.S79504.
#de Leeuw, E.(2014) Efficacy of the small molecule inhibitor of Lipid IIBAS00127538 against Acinetobacter baumannii Drug Design, Development and Therapy 2014:8 1061–1064
Lu, W. and #de Leeuw, E.(2014) Functional intersection of Human Defensin 5 with the TNF receptor pathway. FEBS Letters 588, 1906-1912
Varney K.M., Bonvin, A.M.J.J., Pazgier, M., Malin,J., Yu, W., Ateh, E., Oashi, T., Lu, W., Huang,J., Diepeveen-de Buin, M., Bryant, J., Breukink, E., D. MacKerell Jr.. A. and #de Leeuw, E. (2013) Turning Defense into Offense: Defensin mimetics as novel antibiotics targeting Lipid II. PLOS Pathogens, 2013;9(11):e1003732. doi: 10.1371/journal.ppat.1003732. Epub 2013 Nov 7