• Ph.D., Boston University School of Medicine, 1996
• B.S., State University of New York, 1988

Research Interests: Active mucosal inflammation is characterized by influx of immune cells, especially neutrophils. When occurring in response to a pathogenic microbe, this immune inflammatory response appears to play an important role in locally clearing some infections thus preventing widespread bacterial dissemination in the host. Additionally, such mucosal inflammation can occur in a seemingly inappropriate manner, in the absence of any known pathogens, particularly in chronic inflammatory disease states such as inflammatory bowel disease. The general goal of my research is to elucidate the molecular mechanisms that regulate such mucosal inflammation as these mechanisms are germane to both innate immunity and chronic inflammatory diseases. To date, focusing on the intestine, my colleagues and I have shown that such neutrophil influx is directed via polarized chemokine secretion by the epithelial cells that line the intestine. Specifically, we have shown that pathogens, but not commensal gut microbes activate the pro-inflammatory transcription factor NF-kB in epithelial cells resulting in the secretion of a panel of chemokines that direct neutrophil movement. A most recent finding is that this NF-kB activation results primarily from epithelial contact with bacterial flagellin, a structural component of flagella. Such flagellin is secreted by most gram negative bacteria, including commensal gut E. coli, and thus flagellin is ubiquitous at the apical (lumenal) membrane domain of the intestinal epithelium. However, flagellin can only activate epithelial chemokine secretion when it reaches the basolateral membrane and such flagellin translocation across model epithelia can be mediated by pathogen Salmonella typhimurium but not be commensal E. coli. We found that the epithelial response to flagellin is mediated by the pattern recognition receptor toll-like receptor 5 (TLR5), a receptor whose expression is highly polarized to the basolateral surface. In light of these findings, we hypothesize that translocation of flagellin across the intestinal epithelium and its subsequent activation of basolateral TLR5 is both a mechanism of bacterial pathogenesis and mucosal immunity. Furthermore, aberrant localization of flagellin may play a role in inflammatory bowel disease (IBD). Thus, current specific foci of my research designed to test this hypothesis are as follows: 1) Investigate the mechanism by which S. typhimurium translocate flagellin across polarized intestinal epithelia. 2) Define the signaling pathway by which flagellin induces epithelial pro-inflammatory gene expression. 3) Investigate the role of flagellin in vivo in health (i.e., functional innate immunity) and inflammatory bowel disease.