The research focus of the Selsted laboratory is on peptidic effectors of mammalian innate immunity, specifically the discovery, characterization, and biological roles of defensins. Defensins are antimicrobial peptides expressed in granulocytic leukocytes and epithelial cells. In vitro experiments demonstrate that defensins possess microbicidal activities against bacteria, fungi, and viruses, and transgenic mouse experiments demonstrate that defensins to play a central role in as first line defenders against potentially invasive pathogens in vivo. Three structural defensin subfamilies (α, β, and θ) have been characterized by Selsted and colleagues, each of which possesses a different tri-disulfide motif stabilizing the peptide backbone. α-defensins, the first defensins to be isolated, are expressed predominantly in neutrophils and intestinal Paneth cells. β-defensins, the most ancient of the defensin sub-families (expressed in birds and reptiles), are expressed widely in mammalian epithelia. More recently the Selsted lab isolated θ-defensins from monkey leukocytes. When characterized, these peptides were found to be cyclic molecules, wherein the peptide chain is folded upon itself in a head-to-tail configuration. Current projects in the lab focus on the regulation of α- and θ-defensin expression in leukocyte subsets; post-translational processing pathways; structure-function analysis of natural and synthetic θ-defensins; and the role of defensins as pro- and anti-inflammatory mediators in systemic disease. The lab employs a multidisciplinary approach to questions of defensin biology, employing solid-state chemical synthesis, molecular and cell biology, medical microbiology, structural analyses, and good old fashioned biochemistry.