Michael E. Selsted
Warren L. Bostick Professor and Chairman
    Ph.D., University of California, Los Angeles, 1980
    M.D., University of California, Los Angeles, 1985

Link to CV

UCI Faculty Profile

Research Interests:

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.

Selected Publications:

• Selsted, M.E. and A.J. Ouellette. 1995. Defensins in granules of phagocytic and non-phagocytic cells. Trends Cell Biol. 5:114-119.
  
  
• Hristova, K., M.E. Selsted, and S.H. White. 1997. Critical role of lipid compostion in membrane permeabilization by rabbit neutrophil defensins. J. Biol. Chem. 272:24224-24233
  
  
• 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
  
  
• 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
  
  
• Tang, Y.-Q., J. Yuan, C.J. Miller, and M.E. Selsted. 1999. Isolation, characterization, cDNA cloning, and antimicrobial properties of two distinct subfamilies of -defensins from rhesus macaque leukocytes. Infect. Immun. 67: 6139-6144
  
  
• Ouellette, A.J., D. Darmoul, D. Tran, K.M. Huttner, J. Yuan, and M.E. Selsted. 1999. Peptide localization and gene structure of cryptdin-4, a differentially-expressed mouse Paneth cell -defensin. Infect. Immun. 67:6643-6651.
  
  
• 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.
  
  
• 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.
  
  
• 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. 275:33969-33973.
  
  
• Tran, D., P.A. Tran, Y-Q Tang, J. Yuan, T. Cole, and M.E. Selsted. Homodimeric theta defensins from Rhesus macaque leukocytes. Isolation, synthesis, antimicrobial activities and bacterial binding properties of the cyclic peptides. J. Biol. Chem. In press. (published on line October 23, 2001).