Michael E. Selsted, MD, PhD

Dr. Selsted is a board certified pathologist, physician scientist, and administrator. His academic career includes appointments as Professor (1989-2009) and Chair of Pathology at UC Irvine School of Medicine (2000 – 2009) and Professor and Chair of Pathology in the Keck School of Medicine (2009 – 2024). Dr. Selsted leads a multidisciplinary research program focused on mammalian host defense, innate immunity, and inflammation. This focus led to the discovery and characterization of α-, β-, and θ-defensins, microbicidal and immunomodulatory peptides expressed in myeloid and epithelial cells of vertebrates. These investigations, continuously funded by NIH since 1986, have resulted in more than 50 US and foreign patents, as well as clinical translation of a θ-defensin for treatment of rheumatoid arthritis. Ongoing studies seek to elucidate the immunoregulatory mechanisms of these peptides, design and application of novel analogs, and application of θ-defensin-inspired macrocyclic peptides in models of autoimmune diseases, cancer, and infections caused by MDR bacterial and fungal pathogens.

• Host Defense Peptides as Templates for Antifungal Drug Development J Fungi (Basel). 2020 Oct 23; 6(4). . View in PubMed
• Antimicrob Agents Chemother. 2018 06; 62(6). . View in PubMed
• J Biol Chem. 2018 02 23; 293(8):2725-2734. . View in PubMed
• JCI Insight. 2018 09 20; 3(18). . View in PubMed
• Efficacy of Rhesus Theta-Defensin-1 in Experimental Models of Pseudomonas aeruginosa Lung Infection and Inflammation Antimicrob Agents Chemother. 2017 08; 61(8). . View in PubMed
• Innate Immun. 2015 Jan; 21(1):17-29. . View in PubMed
• Hydrophobic determinants of a-defensin bactericidal activity Infect Immun. 2014 Jun; 82(6):2195-202. . View in PubMed
• Differential Susceptibility of Bacteria to Mouse Paneth Cell a-Defensins under Anaerobic Conditions Antibiotics (Basel). 2014; 3(4):493-508. . View in PubMed
• Antibiotics (Basel). 2014; 3(4):617-31. . View in PubMed
• ImmunologyHD6 defensin nanonets. Science. 2012 Jul 27; 337(6093):420-1. . View in PubMed
• Alternative luminal activation mechanisms for paneth cell a-defensins J Biol Chem. 2012 Mar 30; 287(14):11205-12. . View in PubMed
• High fidelity processing and activation of the human a-defensin HNP1 precursor by neutrophil elastase and proteinase 3 PLoS One. 2012; 7(3):e32469. . View in PubMed
• Cycloquest: identification of cyclopeptides via database search of their mass spectra against genome databases J Proteome Res. 2011 Oct 07; 10(10):4505-12. . View in PubMed
• Criterion for amino acid composition of defensins and antimicrobial peptides based on geometry of membrane destabilization J Am Chem Soc. 2011 May 04; 133(17):6720-7. . View in PubMed
• Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms PLoS One. 2010 Mar 17; 5(3):e9737. . View in PubMed
• Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes Infect Immun. 2008 Dec; 76(12):5883-91. . View in PubMed
• Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins Antimicrob Agents Chemother. 2008 Mar; 52(3):944-53. . View in PubMed
• A pocket guide to explorations of the defensin field Curr Pharm Des. 2007; 13(30):3061-4. . View in PubMed
• Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties J Immunol. 2006 Jan 15; 176(2):1154-62. . View in PubMed
• Mammalian defensins in the antimicrobial immune response Nat Immunol. 2005 Jun; 6(6):551-7. . View in PubMed
• Alpha-defensin expression during myelopoiesis: identification of cis and trans elements that regulate expression of NP-3 in rat promyelocytes J Leukoc Biol. 2004 Feb; 75(2):332-41. . View in PubMed
• alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors AIDS. 2003 Sep 26; 17(14):F23-32. . View in PubMed
• Antimicrobial properties of the Escherichia coli R1 plasmid host killing peptide J Biotechnol. 2003 Jan 09; 100(1):1-12. . View in PubMed
• Antimicrobial peptides from human platelets Infect Immun. 2002 Dec; 70(12):6524-33. . View in PubMed
• Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding proteinA microbicidal granule protein of eosinophils and neutrophils. J Biol Chem. 2002 May 31; 277(22):19658-64. . View in PubMed
• Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells Am J Physiol Gastrointest Liver Physiol. 2002 May; 282(5):G757-65. . View in PubMed
• Homodimeric theta-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides J Biol Chem. 2002 Feb 01; 277(5):3079-84. . View in PubMed
• Cryptdin-3 induces novel apical conductance(s) in Cl- secretory, including cystic fibrosis, epithelia . 2001 Feb; 280(2):C296-302. . View in PubMed
• Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans Infect Immun. 2000 Nov; 68(11):6257-64. . View in PubMed
• Characterization of luminal paneth cell alpha-defensins in mouse small intestineAttenuated antimicrobial activities of peptides with truncated amino termini. J Biol Chem. 2000 Oct 27; 275(43):33969-73. . View in PubMed
• Identification of constituents of human neutrophil azurophil granules that mediate fungistasis against Histoplasma capsulatum Infect Immun. 2000 Oct; 68(10):5668-72. . View in PubMed
• Formation and characterization of a single Trp-Trp cross-link in indolicidin that confers protease stability without altering antimicrobial activity J Biol Chem. 2000 Apr 21; 275(16):12017-22. . View in PubMed
• Isolation, characterization, cDNA cloning, and antimicrobial properties of two distinct subfamilies of alpha-defensins from rhesus macaque leukocytes Infect Immun. 1999 Nov; 67(11):6139-44. . View in PubMed
• A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins Science. 1999 Oct 15; 286(5439):498-502. . View in PubMed
• CD spectra of indolicidin antimicrobial peptides suggest turns, not polyproline helix Biochemistry. 1999 Sep 21; 38(38):12313-9. . View in PubMed
• Cloning and expression of bovine neutrophil beta-defensinsBiosynthetic profile during neutrophilic maturation and localization of mature peptide to novel cytoplasmic dense granules. J Biol Chem. 1999 Sep 10; 274(37):26249-58. . View in PubMed
• Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils J Leukoc Biol. 1998 Jan; 63(1):94-100. . View in PubMed
• Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins J Biol Chem. 1997 Sep 26; 272(39):24224-33. . View in PubMed
• Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3 Proc Natl Acad Sci U S A. 1997 Aug 05; 94(16):8585-9. . View in PubMed
• Bilayer interactions of indolicidin, a small antimicrobial peptide rich in tryptophan, proline, and basic amino acids Biophys J. 1997 Feb; 72(2 Pt 1):794-805. . View in PubMed
• Cryptdin gene expression in developing mouse small intestine Am J Physiol. 1997 Jan; 272(1 Pt 1):G197-206. . View in PubMed
• HPLC methods for purification of antimicrobial peptides Methods Mol Biol. 1997; 78:17-33. . View in PubMed
• Interactions of monomeric rabbit neutrophil defensins with bilayers: comparison with dimeric human defensin HNP-2 Biochemistry. 1996 Sep 10; 35(36):11888-94. . View in PubMed
• Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with in vivo antifungal activity Biochim Biophys Acta. 1995 Jul 26; 1237(2):109-14. . View in PubMed
• Defensins in granules of phagocytic and non-phagocytic cells Trends Cell Biol. 1995 Mar; 5(3):114-9. . View in PubMed
• Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides Infect Immun. 1994 Dec; 62(12):5397-403. . View in PubMed
• In vitro activity of naturally occurring peptides (defensins) against Listeria monocytogenes Cad Saude Publica. 1994 Dec; 10(4):440-5. . View in PubMed
• Mouse Paneth cell defensins: primary structures and antibacterial activities of numerous cryptdin isoforms Infect Immun. 1994 Nov; 62(11):5040-7. . View in PubMed
• Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores Protein Sci. 1994 Sep; 3(9):1362-73. . View in PubMed
• Myeloperoxidase (MPO) gene mutation in hereditary MPO deficiency Blood. 1994 Apr 01; 83(7):1935-40. . View in PubMed
• Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro Antimicrob Agents Chemother. 1993 Dec; 37(12):2628-32. . View in PubMed
• Molecular analysis of myeloperoxidase deficiency shows heterogeneous patterns of the complete deficiency state manifested at the genomic, mRNA, and protein levels Blood. 1993 Aug 15; 82(4):1317-22. . View in PubMed
• Defensins promote fusion and lysis of negatively charged membranes Protein Sci. 1993 Aug; 2(8):1301-12. . View in PubMed
• Defensins are mitogenic for epithelial cells and fibroblasts J Cell Physiol. 1993 May; 155(2):408-13. . View in PubMed
• Characterization of the disulfide motif in BNBD-12, an antimicrobial beta-defensin peptide from bovine neutrophils J Biol Chem. 1993 Mar 25; 268(9):6649-53. . View in PubMed
• Investigational approaches for studying the structures and biological functions of myeloid antimicrobial peptides Genet Eng (N Y). 1993; 15:131-47. . View in PubMed
• Enteric defensins: antibiotic peptide components of intestinal host defense J Cell Biol. 1992 Aug; 118(4):929-36. . View in PubMed
• Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils J Biol Chem. 1992 Mar 05; 267(7):4292-5. . View in PubMed
• Bactericidal potency and mechanistic specificity of neutrophil defensins against bovine mastitis pathogens Vet Microbiol. 1991 Sep; 29(1):49-58. . View in PubMed
• Antimicrobial activity of rabbit leukocyte defensins against Treponema pallidum subsppallidum. Infect Immun. 1991 Apr; 59(4):1359-67. . View in PubMed
• Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization Science. 1991 Mar 22; 251(5000):1481-5. . View in PubMed
• Defensins: endogenous antibiotic peptides of animal cells Cell. 1991 Jan 25; 64(2):229-30. . View in PubMed
• Killing of oral, gram-negative, facultative bacteria by the rabbit defensin, NP-1 Oral Microbiol Immunol. 1990 Dec; 5(6):315-9. . View in PubMed
• In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins Infect Immun. 1990 Dec; 58(12):3934-40. . View in PubMed
• Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium Infect Immun. 1990 Nov; 58(11):3706-10. . View in PubMed
• In vitro antimicrobial activity of defensins against ocular pathogens Arch Ophthalmol. 1990 Jun; 108(6):861-4. . View in PubMed
• Defensins Eur J Haematol. 1990 Jan; 44(1):1-8. . View in PubMed
• Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes Proc Natl Acad Sci U S A. 1990 Jan; 87(1):210-4. . View in PubMed
• Monocyte-chemotactic activity of defensins from human neutrophils J Clin Invest. 1989 Dec; 84(6):2017-20. . View in PubMed
• Interaction of human defensins with Escherichia coliMechanism of bactericidal activity. J Clin Invest. 1989 Aug; 84(2):553-61. . View in PubMed
• Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency Blood. 1989 May 15; 73(7):1980-6. . View in PubMed
• Determination of the disulfide array in the human defensin HNP-2A covalently cyclized peptide. J Biol Chem. 1989 Mar 05; 264(7):4003-7. . View in PubMed
• Neutrophils and host defense Ann Intern Med. 1988 Jul 15; 109(2):127-42. . View in PubMed
• Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations J Clin Invest. 1988 Jun; 81(6):1829-35. . View in PubMed
• Characterization of two crystal forms of human defensin neutrophil cationic peptide 1, a naturally occurring antimicrobial peptide of leukocytes J Biol Chem. 1988 Apr 25; 263(12):5933-5. . View in PubMed
• Mechanism of target cytolysis by peptide defensinsTarget cell metabolic activities, possibly involving endocytosis, are crucial for expression of cytotoxicity. J Immunol. 1988 Apr 15; 140(8):2686-94. . View in PubMed
• Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophils Biochem Pharmacol. 1988 Mar 01; 37(5):951-6. . View in PubMed
• Defensin-rich dense granules of human neutrophils Blood. 1987 Sep; 70(3):757-65. . View in PubMed
• Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species Nucleic Acids Res. 1987 Mar 11; 15(5):2013-28. . View in PubMed
• In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes Blood. 1986 Dec; 68(6):1407-10. . View in PubMed
• Direct inactivation of viruses by human granulocyte defensins J Virol. 1986 Dec; 60(3):1068-74. . View in PubMed
• In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoalveolar macrophages J Infect Dis. 1986 Sep; 154(3):483-9. . View in PubMed
• Antimicrobial activity of phagocyte granule proteins Semin Respir Infect. 1986 Jun; 1(2):107-17. . View in PubMed
• Eosin Y: a reversible stain for detecting electrophoretically resolved protein Anal Biochem. 1986 Jun; 155(2):270-4. . View in PubMed
• DefensinsNatural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct; 76(4):1427-35. . View in PubMed
• Newborn rabbit alveolar macrophages are deficient in two microbicidal cationic peptides, MCP-1 and MCP-2 Am Rev Respir Dis. 1985 Oct; 132(4):901-4. . View in PubMed
• Activity of rabbit leukocyte peptides against Candida albicans Infect Immun. 1985 Jul; 49(1):202-6. . View in PubMed
• Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity Infect Immun. 1985 Jul; 49(1):207-11. . View in PubMed
• Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics from rabbit leukocytes J Virol. 1985 May; 54(2):467-72. . View in PubMed
• In vitro effect of phagocyte cationic peptides on Coccidioides immitis J Infect Dis. 1985 May; 151(5):890-4. . View in PubMed
• Divergent expression of cytotoxic and microbicidal functions of rabbit alveolar and peritoneal macrophages: effects of non-specific activation and a natural microbicidal peptide, MCP-1 Aust J Exp Biol Med Sci. 1985 Feb; 63 ( Pt 1):53-63. . View in PubMed
• Characterization of two crystal forms of neutrophil cationic protein NP2, a naturally occurring broad-spectrum antimicrobial agent from leukocytes J Mol Biol. 1984 Sep 25; 178(3):783-5. . View in PubMed
• Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages Infect Immun. 1983 Oct; 42(1):10-4. . View in PubMed
• Isolation and purification of bactericides from human tears Exp Eye Res. 1982 Mar; 34(3):305-18. . View in PubMed
• Increased content of microbicidal cationic peptides in rabbit alveolar macrophages elicited by complete Freund adjuvant Infect Immun. 1981 Sep; 33(3):775-8. . View in PubMed
• Microbicidal and cytotoxic properties of soluble components from quaternary aminoethyl-sephadex Infect Immun. 1980 Dec; 30(3):887-9. . View in PubMed
• A simple and ultrasensitive enzymatic assay for the quantitative determination of lysozyme in the picogram range Anal Biochem. 1980 Nov 15; 109(1):67-70. . View in PubMed
• Lysozyme: primary bactericidin in human plasma serum active against Bacillus subtilis Infect Immun. 1978 Jun; 20(3):782-91. . View in PubMed