Innate immunity, immunology, host defense, mucosal immunity, antimicrobial peptides, wound healing, developmental immunology
Emil Bogen Prize, 1985; UCLA Alumni Award of Excellence, 1985; Athalie Clarke Research Award, 1993; ASCI, 1994; Alpha Omega Alpha Medical Honor Society, 2000; Warren L. Bostick Endowed Professor; NIH MERIT award, 2000; Association of American Physicians, 2001
Dr. Selsted and his collaborators have discovered and characterized several families of antimicrobial peptides which are produced by immune cells of higher mammals. Termed alpha-, beta-, and theta-defensins, these peptides provide the host with the ability to fend off potentially invasive pathogens. The recently characterized theta-defensins are cyclic molecules, and represent the first example of this molecular motif in animals.
Defensins possess potent antimicrobial activities against bacteria, fungi, certain viruses, protozoa, and they also have cytotoxic activity against tumor cells. The antimicrobial properties are unique in that resistant bacteria do not arise from repeated passage in the presence of sublethal peptide concentrations.
Some defensins are produced in the lining of the small intestine and are secreted into its lumen. This finding demonstrates that defensins are tolerated on normal tissue surfaces, and suggests that defensin-like peptides may have therapeutic utility.
Ongoing studies are focused on 1) characterizing the process of the cyclization process that gives rise to the novel circular structure of theta defensins, 2) biophysical characterization of antimicrobial mechanisms, and 3) analysis of the regulation of defensin gene expression.
Issued U.S. Patents
Cationic Oligopeptides Having Microbicidal Activity
U.S. 4,543,252 Sept. 24, 1985
U.S. 4,659,692 April 21, 1987
U.S. 4,705,777 Nov. 10, 1987
Defensin Peptide Compositions and Methods for Their Use:
U.S. 5,242,902 Sept. 7, 1993
Broad Spectrum Antimicrobial Compounds and Methods of Use.
U.S. 5,324,716 June 28, 1994
U.S. 5,547,939 August 20, 1996
Antimicrobial Peptides, Antibodies, and Nucleic Acid Molecules from Bovine Neutrophils.
U.S. 5,459,235 October 17, 1995
Antibiotic Cryptdin Peptides and Methods of Their Use.
U.S. 5,422,424 June 6, 1995
U.S. 5,731,149 March 24, 1998
U.S. 5,840,498 November, 24, 1998
U.S. 5,844,072 December 1, 1998
U.S. 6,300,470 October. 9, 2001
Antimicrobial Peptides from Bovine Neutrophils
U.S. 5,821 224 October 13, 1998
Antimicrobial Peptides and Methods of Use
U.S. 6,008,195 December 28, 1999
Preparation of Antibiotic Cryptdin Peptides
U.S. 6,057,425 May 2, 2000
Novel Antimicrobial Peptides from Bovine Neutrophils
U.S 6,211,148 April 3, 2001
Indolicidin Analogs and Methods of Using Same
U.S. 6,303,575 October 16, 2001
Antimicrobial Theta defensins
U.S. 6,335,318 January 1, 2002
Crosslink-stabilized Indolicidin Analogs
U.S. 6,444,645 October 1, 2002
Self-preserving multipurpose ophthalmic solutions incorporating a polypeptide antimicrobial
US. 6,482,799 Nov. 19, 2002
Antimicrobial Theta defensins and Methods of Use
U.S. 6,514,727 Feb. 4, 2003
Indolicidin Analogs and Methods of Using Same
U.S. 6,524,585 Feb. 25, 2003
Tang, Y.-Q., J. Yuan, G. Ösapay, K. Ösapay, D. Tran, C.J. Miller, A. J. Ouellette, and M.E.Selsted. 1999. A cyclic antimicrobial peptide produced in primate leukocytes the ligation of two truncated alpha-defensins. Science 286:498-502.
Yount, N.Y., J. Yuan, A. Tarver, G. Diamond, P.A. Tran, J.N. Levy, C. McCullough, J.S. Cullor, C.L. Bevins, and M.E. Selsted. 1999. Cloning and expression of bovine neutrophil beta-defensins. Biosynthetic profile during neutrophilic maturation and localization of mature peptide to novel cytoplasmic dense granules. J. Biol. Chem. 274:26249-26258.
Ouellette, A.J., D. Satchell, M. M. Hsieh, S. J. Hagen and M. E. Selsted. 2000. Characterization of luminal Paneth cell alpha-defensins in mouse small intenstine: attenuated antimicrobial activities of peptides with truncated amino termini. J. Biol. Chem.
Ösapay, K., D. Tran, A.S. Ladokhin, S.H. White, A.H. Henschen, and M.E. Selsted. 2000. Formation and characterization of a single Trp-Trp crosslink in indolicidin that confers protease stability without
altering antimicrobial activity. J. Biol. Chem. 275: 12017-12022.
Tran, D., P.A. Tran, Y-Q Tang, J. Yuan, T. Cole, and M.E. Selsted. 2002. Homodimeric theta defensins from Rhesus macaque leukocytes. Isolation, synthesis, antimicrobial activities and bacterial binding properties of the cyclic peptides. J. Biol. Chem. 277: 3079-3084
Ayabe, T., D.P. Satchell, C.L. Wilson, W.C. Parks, M.E. Selsted, and A.J. Ouellette. 2000. Secretion of microbicidal a-defensins by intestinal Paneth cells in response to bacteria. Nature Immunology, 1:113-118.
Tydell, C.C., N.Y. Yount, D. Tran, J. Yuan and M.E. Selsted. 2002. Isolation, characterization, and antimicrobial properties of bovine oligosaccharide binding protein. A microbicidal granule protein of eosinophils and neutrophils. J. Biol. Chem. 277: 19658-19664.
Selsted, M.E. 2004. Theta-Defensins: cyclic antimicrobial peptides produced by binary ligation of truncated a-defensins. Curr. Prot. Peptide Sci. in press.
NIH. R37 AI22931-15-24. Molecular Aspects of Leukocyte Antimicrobial Peptides; 4-1-00 to 3-30-10; P.I., M.E. Selsted;
NIH. RO1 DE 155170-01-04. Molecular Ontogeny of Oral Mucosal Resistance to SIV; 12-15-03 to 11-30-07; P.I., M.E. Selsted
American Association for the Advancement of Science,
American Federation for Medical Research,
American Peptide Society,
American Society for Clinical Research
American Society for Microbiology,
American Society of Biochemistry and Molecular
American Society of Hematology,
College of American Pathologist (Fellow),
Society for Leukocyte Biology,
The Protein Society
Western Society for Clinical Investigation
Diplomate, American Board of Pathology - 1990
Immunology and Pathogenesis