Assistant Professor of Research
Keck School of Medicine
- Antimicrobial peptides
- Innate Immunity
Research OverviewMammalian defensins are small cationic tri-disulfide linked, broad spectrum, antimicrobial peptides produced in diverse cells and tissues that are most likely to come in contact with pathogenic microorganisms. Three structural classes of defensins have been identified in mammals: α-, β- and θ-defensins. The α- and β-defensins are peptides of about 25-45 amino acid residues produced by the proteolytic processing of precursor polypeptides. The θ-defensins are unique since they are the only known cyclic peptides found in the Animal kingdom. These 18 amino acid residue circular peptides are produced by the head to tail ligation of nomamer sequences from two precursor polypepitdes. We are using cellular and biochemical approaches to elucidate the factors involved in biosynthesis of defensins.
In addition to their role as antimicrobial peptides, defensins also play a regulatory role in innate and adaptive immunity and in diverse cellular processes. Our results have demonstrated an anti-inflammatory role for θ-defensins in regulating inflammation in cellular and animal models of inflammation. We have shown that the θ-defensin, RTD-1, inhibits NF-κB and the MAP kinase signaling pathways by stimulating the phosphorylation of Akt. Studies are in progress to identify the cellular receptor and to understand the molecular bases for the anti-inflammatory effects of θ-defensin and for their potential applications as therapeutics for inflammatory diseases.