Andre J. Ouellette

Professor, Pathology
School of Medicine

Professor, Microbiology & Molecular Genetics
School of Medicine

Ph.D., Indiana University, 1972, Microbiology

B.S., University of Maine, Orono, 1969, Bacteriology

Phone: (949) 824-4647
Fax: (949) 824-1098

University of California, Irvine
Room 160B, Medical Surge I
Department of Pathology
Mail Code: D-44
Irvine, CA 92697-480

Paneth cell, antimicrobial peptide, development, defensin
The goals of this research program are to define mechanisms of innate immunity in the mammalian intestinal epithelium, focusing almost exclusively on the biology of the Paneth cell. In the small intestine, these cells secrete very large granules into the lumen of the crypts of Lieberkòhn, and those granule constituents include many antimicrobial peptides. Among the Paneth cell secretory products are approximately 20 different a-defensins, also known as cryptdins, as well as additional peptides coded by related genes in this family. Paneth cells secrete granules when exposed to bacteria or bacterial antigens, and the majority of the bactericidal activity in the secretion is due to cryptdins. It is the central hypothesis of the lab that these molecules function as endogenous antibiotics that influence the microenvironment of the crypt. The hypothesis is being tested by two primary approaches. First, the mechanisms that regulate a-defensin biosynthesis in fully-differentiated and developing Paneth cells are being investigated, and second, the biological activities and mode(s) of action of individual mouse a-defensins are being determined.
Publications Maemoto, A., Qu, X., Rosengren, K.J., Tanabe, H., Henschen-Edman, A., Craik, D.J., and Ouellette, A.J.: Functional analysis of the alpha-defensin disulfide array in mouse cryptdin-4. J. Biol. Chem., in press, 2004.
  Tanabe, H., Qu, X., Weeks, C.S., Cummings, J.E., Kolusheva, S., Walsh, K.B., Jelinek, R., Vanderlick, T.K., Selsted, M.E., and Ouellette, A.J.: Structure-activity determinants in Paneth cell alpha-defensins: Loss-of-function in mouse cryptdin-4 by charge-reversal at arginine residue positions, J. Biol. Chem. 279: 11976-11983, 2004.
  Tanabe, H., Yuan, J., Zaragoza, M.M., Dandekar, S., Henschen-Edman, A., Selsted, M.E., and Ouellette, A.J.: Paneth cell alpha-defensins from rhesus macaque small intestine. Infect. Immun., 72: 1470-1478, 2004. 2004.
  Satchell, D.P., Sheynis, T., Shirafuji, Y., Kolusheva, S., Ouellette, A.J., and Jelinek, R.: Interactions of mouse Paneth cell alpha-defensins and alpha-defensin precursors with membranes: Prosegment inhibition of peptide association with biomimetic membranes. J. Biol. Chem. 278:13838-13846, 2003.
  Shirafuji, Y., Tanabe, H., Satchell, D.P., Henschen-Edman, A., Wilson, C.L., Ouellette, A.J.: Structural determinants of procryptdin recognition and cleavage by matrix metalloproteinase-7. J. Biol. Chem, 278: 7910-7919, 2003.
  Ayabe, T., Satchell, D.P., Pesendorfer, P., Tanabe, H., Wilson, C.L., Hagen, S.J., Ouellette, A.J.: Activation of alpha-defensins in mouse intestinal Paneth cells, J. Biol. Chem. 277:5219-5228, 2002
  Ayabe, T., Wulff, H., Darmoul, D., Cahalan, M.D., Chandy, K.G., and Ouellette, A.J.: Modulation of mouse Paneth cell a-defensin secretion by mIKCa1, a Ca2+-activated,intermediate-conductance potassium channel, J. Biol. Chem. 277:3793-3800, 2002.
  Ayabe, T., Satchell, D.P., Wilson, C.L., Parks, W.C., Selsted, M.E., Ouellette, A.J.: Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nature Immunol. 1:113-118, 2000.
  Wilson, C.L., Ouellette, A.J., Satchell, D.P., Ayabe, T., López-Boado, Y.S., Stratman, J.L., Hultgren, S.J., Matrisian, L.M., and Parks, W.C.: Regulation of intestinal a-defensin activation by the metalloproteinase matrilysin in innate host defense, Science 286:113-117, 1999.
  Tang, Y. -Q., Yuan, J., Ösapay, K., Ösapay, G., Tran, D., Miller, C.J., Ouellette, A.J., and Selsted, M.E.: A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science 286:498-502, 1999.
Grants NIH 2 R01 DK 4632-13 Ouellette (PI) 05/01/00-04/30/05 Peptide effectors of enteric host defense
Human Frontiers Science Program Gizeli (PI) 08-01-04 to 07-31-07 Mechanisms of antimicrobial peptide interactions with the target cell membrane
U.S.-Israel Binational Science Fdn (Jelinek, Ouellette, Co-PIs) 09/01/02-08/31/06 Novel biomimetic approaches to investigate defensin microbicidal mechanisms.
American Society for Biochemisty and Molecular Biology, American Society for Microbiology, American Gastroenterological Associatio
Graduate Programs Immunology and Pathogenesis

Research Center Center for Immunology
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Last updated 09/15/2004