Pathology & Laboratory Medicine
Keck School of Medicine
USC / Norris Comprehensive Cancer Center
Innate immunity and inflammation in the gastrointestinal tract
Paneth cell biology
The Ouellette lab investigates the role of α-defensins secreted by small intestinal Paneth cells in establishment of innate mucosal immunity of the lower gastrointestinal tract. The lab studies the mechanisms that regulate α-defensin biosynthesis and posttranslational conversion to active forms in cells of myeloid origin, in Paneth cells, and in the intestinal lumen. Structure-activity relationships in mouse and primate α-defensins and their precursors are being studied by site-directed mutagenesis at charged, aliphatic, and canonical residue positions, and determinants of bactericidal activity against varied species of bacteria and fungi are being investigated. NMR-based approaches are disclosing the specific role(s) of surface charge and aliphatic side chains in bacterial cell envelope disruption to elucidate mechanisms of α-defensin bactericidal activity. α-Defensin biosynthesis is being studied by functional analysis of differentially expressed Paneth cell and myeloid defensin genes to define transcriptional and posttranslational processing mechanisms. Paneth cell biology and the role of Paneth cell homeostasis are investigated in fetal and newborn mice and during inflammation associated with selective gene knockouts.