1994: B.S./B.A. University of Rochester
2002: Ph.D., Microbiology, University of California at Davis
2002-2004: Postdoctoral Fellowship, University of Maryland Institute of Human Virology
2005-2009: Scientist, Dow Pharmaceutical Sciences
2010: Visiting Scholar, University of California at Davis
2010-2011: Microbiologist, Food and Drug Adminsitration
2011-Present: Research Associate, Institute of Human Virology, University of Maryland School of Medicine
I am currently studying the structure and function of peptides such as the human alpha defensins with Dr. Wuyuan Lu. Antimicrobial peptides constitute a commonly deployed defensive strategy in the war against disease. They are found throughout the tree of life. Taking advantage of the protein scaffold and the cellular equipment of transcription and translation, over evolutionary time scales antimicrobial peptides are mutable and often quite versatile, acquiring new functions as they strive to keep the host free from invaders. The same peptide might bind and disrupt a wide variety of target molecules, including lipids, carbohydrates, and proteins. An example of this type of multifunctional antimicrobial peptide is the defensins, which are active against a multitude of potentially dangerous microbes. For example, defensins can provide a measure of protection against Bacillus anthracis by binding and inhibiting anthrax lethal factor, an enzyme required to form anthrax toxin. Defensins are active against human immunodeficiency virus (HIV), herpes simplex virus (HSV), human adenoviruses (AdV), human papillomaviruses (HPV), and other viruses. Defensins are also bactericidal against both Gram-positive and Gram-negative bacteria.
The Virtual Colony Count Antibacterial Assay
We developed a kinetic, 96-well turbidimetric procedure called "virtual colony count" that is capable of testing the antimicrobial properties of six antimicrobial peptides concurrently on a single microplate. Its use has clarified the relative potencies of human alpha defensins and a wide array of mutants and raised intriguing questions about differences in activity against Gram-positive and Gram-negative bacteria. It has demonstrated the functional consequences of perturbing such structural features as a conserved beta bulge, salt bridges, and hydrophobic dimer interfaces. We have also studied enantiomeric defensins made of all D-amino acids. These studies depict antimicrobial activity that operates by two mechanistic principles: membrane disruption and lipid II binding. Learning the details of defensin antibacterial activity has led us to find ways to improve their suitability as antimicrobial agents that could be used to treat infections.
Wu Z, Prahl A, Powell R, Ericksen B, Lubkowski J, Lu W. From pro defensins to defensins: synthesis and characterization of human neutrophil pro alpha-defensin-1 and its mature domain. J Pept Res. 2003 Aug;62(2):53-62.
Wu Z, Alexandratos J, Ericksen B, Lubkowski J, Gallo RC, Lu W. Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: structural and mechanistic implications of p17 myristoylation. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11587-92.
Wu Z, Ericksen B, Tucker K, Lubkowski J, Lu W. Synthesis and characterization of human alpha-defensins 4-6. J Pept Res. 2004 Sep;64(3):118-25.
Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human alpha defensins. Antimicrob Agents Chemother. 2005 Jan;49(1):269-75.
Wu Z, Cocchi F, Gentles D, Ericksen B, Lubkowski J, Devico A, Lehrer RI, Lu W. Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 2005 Jan 3;579(1):162-6.
Xie C, Prahl A, Ericksen B, Wu Z, Zeng P, Li X, Lu WY, Lubkowski J, Lu W. Reconstruction of the conserved beta-bulge in mammalian defensins using D-amino acids. J Biol Chem. 2005 Sep 23;280(38):32921-9.
Xie C, Zeng P, Ericksen B, Wu Z, Lu WY, Lu W. Effects of the terminal charges in human neutrophil alpha-defensin 2 on its bactericidal and membrane activity. Peptides. 2005 Dec;26(12):2377-83.
Wu Z, Li X, de Leeuw E, Ericksen B, Lu W. Why is the Arg5-Glu13 salt bridge conserved in mammalian alpha-defensins? J Biol Chem. 2005 Dec 30;280(52):43039-47.
Wu Z, Li X, Ericksen B, de Leeuw E, Zou G, Zeng P, Xie C, Li C, Lubkowski J, Lu WY, Lu W. Impact of pro segments on the folding and function of human neutrophil alpha-defensins. J Mol Biol. 2007 Apr 27;368(2):537-49.
Mayhew JW, Gideon LT, Ericksen B, Hlavaty JJ, Yeh SM, Chavdarian CG, Strick N, Neurath AR. Development of a gel permeation chromatographic assay to achieve mass balance in cellulose acetate phthalate stability studies. J Pharm Biomed Anal. 2009 Feb 20;49(2):240-6.
Wei G, de Leeuw E, Pazgier M, Yuan W, Zou G, Wang J, Ericksen B, Lu WY, Lehrer RI, Lu W. Through the looking glass: mechanistic insights from enantiomeric human defensins. J Biol Chem. 2009 Oct 16;284(42):29180-92.
Pazgier M, Wei G, Ericksen B, Jung G, Wu Z, de Leeuw E, Yuan W, Szmacinski H, Lu WY, Lubkowski J, Lehrer RI, Lu W. Sometimes it takes two to tango: contributions of dimerization to functions of human α-defensin HNP1 peptide. J Biol Chem. 2012 Mar 16;287(12):8944-53.
Zhao L, Ericksen B, Wu X, Zhan C, Yuan W, Li X, Pazgier M, Lu W. Invariant Gly Residue Is Important for α-Defensin Folding, Dimerization, and Function: A Case Study of the Human Neutrophil α-Defensin HNP1. J Biol Chem. 2012 Jun 1;287(23):18900-12.
Rajabi M, Ericksen B, Wu X, de Leeuw E, Zhao L, Pazgier M, Lu W. Functional Determinants of Human Enteric α-Defensin HD5: Crucial Role for Hydrophobicity at Dimer Interface. J Biol Chem. 2012 Jun 22;287(26):21615-27
Xu S, Li H, Shao XX, Fan C, Ericksen B, Liu J, Chi C, Wang C. Critical effect of peptide cyclization on the potency of peptide inhibitors against Dengue virus NS2B-NS3 protease. J Med Chem. 2012 Aug 9;55(15):6881-7.
Pazgier M, Ericksen B, Ling M, Toth EA, Shi J, Li X, Galliher-Beckley A, Lan L, Zou G, Zhan C, Yuan W, Pozharski E, Lu W. Structural and functional analysis of the pro-domain of human cathelicidin, LL-37. Biochemistry. 2013 Feb 13.
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