UC Davis One Shields Avenue Rm 5515 Genome and Biomedical Sciences Building Davis, CA 95616 Tel: (530) 754-6889 Lab: (530) 754-6679 FAX: (530) 754-7240 CLBevins@ucdavis.edu

University of Maryland B.A. Biology
University of Maryland M.D. Medicine
University of Maryland Ph.D. Biochemistry

Member of the Graduate Groups of Immunology, Microbiology, Biochemistry & Molecular Biology

Innate Immune Responses; Mucosal Immunology; Antimicrobial Peptides

• Characterization of Antimicrobial Peptides from Human and Rodent Mucosal Tissues
• Study of the Regulated Expression and Processing of Antimicrobial Peptides
• In vivo models of defensin activity
• Altered Expression of Antimicrobial Peptides in Inflammatory Bowel Disease and Otitis Media

Our laboratory is interested in innate immunity of mucosal tissues and we are focused on a newly discovered component of host defense: antimicrobial peptides. Antimicrobial peptides are endogenous antibiotics, isolated from diverse species throughout the plant and animal kingdoms. They represent an evolutionary ancient mechanism of host defense. These peptides have a broad-spectrum of antimicrobial activity that includes bacteria, fungi and certain viruses. Their antimicrobial activity is attributed to their ability to selectively disrupt microbial membrane functions at micromolar concentrations. Additional biological activities of many antimicrobial peptides (for example, chemotaxis) are a result of high affinity interactions with various cell surface receptors. Defensins are the major class of antimicrobial peptides in humans and other mammals.

Recent work from our laboratory has discovered that certain defensins are expressed in abundance by epithelial cells at wet mucosal surface. The long-range goal of our research is to understand the specific role that these epithelial antimicrobial peptides play in mucosal host defense and to characterize the pathophysiology that characterizes altered expression of these peptides. Although the epithelia of mammalian mucosal tissues were once regarded as a primarily a passive barrier to noxious agents, our recent work supports a model: Induction of antimicrobial peptide expression by bacterial and pro-inflammatory stimuli constitutes part of an active, early host defense response of challenged epithelial cells. Our current collaborative studies include: (i) characterizing the primary structure and biological activity of the tissue forms defensins, (ii) defining the key regulatory steps for the expression of these molecules, (iii) exploring potential mechanisms of therapeutic modulation of these systems. The investigations include biochemical and molecular biological approaches and analysis of transgenic models.

Wehkamp J, Salzman NH, Porter E, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima JH, Fellermann K, Ganz T, Stange EF, Bevins CL. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 102, 18129-18134, 2005.

Sherman MP, Bennett SH, Hwang FFY, Sherman J, Bevins CL. Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine. Infect. Immun. 73:6143-6146, 2005.

Salzman N, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Human defensin-5 gene in transgenic mice: Paneth cell specific expression and protection from lethal Salmonella typhimurium infection. Nature 422:522-526, 2003.

Ghosh D, Porter EM, Shen B, Lee SK, Wilk DJ, Crabb JW, Drazba J, Yadav SY, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat. Immunol. 3:583-590, 2002.

Jia H-P, Wowk SA, Schutte BC, Lee SK, Vivado A, Tack BF, Bevins CL, McCray Jr PB. A novel murine b-defensin expressed in tongue, esophagus and trachea. J. Biol. Chem. 275:33314-33320, 2000.

Diamond G, Kaiser V, Rhodes J, Russell J, Bevins C. Transcriptional regulation of b-defensin gene expression in tracheal epithelial cells. Infect Immun 68: 113-119, 2000.

Yount NY, Yuan J, Tarver AP, Diamond G, Levy JN, McGuire PA, McCullogh C, Cullor JS, Bevins CL, Selsted ME. Molecular cloning and expression of bovine neutrophil b-defensin 4. Characterization of cDNA and genomic sequences, pattern of tissue expression, and localization of the fully-processed peptide to neutrophil dense granules. J. Biol. Chem. 274: 26249-26258, 1999.

Tarver AP, Clark DP, Diamond G, Russell JP, Erdjument-Bromage H, Tempst P, Cohen K, Jones DE, Sweeney RW, Wines M, Huang S, Bevins CL. Enteric beta-Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvum Infection. Infection and Immunity 66: 1045-56, 1998.

Diamond G, Russell JP, Bevins CL. Inducible expression of an endogenous antibiotic in lipopolysaccharide-challenged tracheal epithelial cells. PNAS 93: 5156-5160, 1996.

Mallow EM, Harris A, Salzman N, Russell JP, DeBerardinis JP, Ruchelli E, Bevins CL. Human enteric defensins: Gene structure and developmental expression. J. Biol. Chem. 271: 4038-4045, 1996.