Our major research interest is to elucidate the etiologic agents isolated from pathogenic bacteria related to the worldwide emerging and re‐emerging diseases.

Studies on the cellular and molecular mechanisms of diarrhea induced by bacterial enterotoxins:
　　Aeromonas sobria hemolysin is important in the pathogenesis of diarrhea caused by this enteropathogenic bacterium. By immunoprecipitation analysis using hemolysin and anti‐hemolysin antibody, a ６６‐kDa protein （p６６） was identified as a receptor for A. sobria hemolysin on Intestine ４０７ cells. The p６６ was found to be a glycosylphosphatidylinositol‐anchored glycoprotein expressed on the surface of Intestine ４０７ cells. （Ref. Microb. Pathog. （１９９９）２７：２１５）
　　Focusing on the molecular mechanisms of the diarrhea induced by heat‐stable enterotoxins （STd） of enteropathogenic bacteria, we are also studying １）interaction of Escherichia coli heat‐stable enterotoxin with its receptor and ２）activation of guanylate cyclase（GC‐C）by STa.（Ref. Eur. J. Biochem．（１９９９）２６３：３３８）

Studies on the pathogenesis of Helicobacter pylori:
　　To investigate a potential mechanism of how H. pylori establishes infection, we investigates the host‐parasite relationships of H. pylori, focusing on vacuolating cytotoxin A （VacA）and Cag pathogenicity island （Cag PAI）.
　　１）VacA exposed to alkaline or acid conditions, with subsequent neutralization, exhibits enhanced vacuolating activity;the acid or alkali‐activated VacA appears to bind a cell surface receptor protein of 〜２５０kDa. N‐terminal and internal amino acid sequence is consistent with the hypothesis that p２５０ is RPTPβ. Phorbolmyristate （PMA, TPA） induces differentiation of the human leukemic cell line HL‐６０ into cells with macrophage‐like characteristics and enhances the susceptibility of HL‐６０ cells to VacA. PMA induced expression of RPTPβmRNA and protein as determined by RT‐PCR and indirect immunofluorescence studies. Vitamin D３ and IFN‐γ, which stimulate defferentiation of HL‐６０ cells into a monocyte‐like cells, also induced VacA sensitivity and expression of RPTPβ mRNA, whereas １．２％ DMSO and retinoic acid, which stimulated the maturation of HL‐６０ into granulocyte‐like cells did not. RPTPβ anti‐sense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTPβ. Double immunostaining studies also indicated that newly expressed RPTPβ colocalized with VacA in PMA‐treated HL‐６０ cells. BKN‐２１ cells transfected with the RPTPβ cDNA acquired VacA sensitivity. All data are consistent with the conclusion that acquisition of VacA sensitivity by PMA‐treated HL‐６０ cells results from induction of RPTPβ, a protein that function as the VacA receptor. (Ref. J. Biol. Chem.（１９９９）２７４：３６６９３，J. Biol.Chem.（２０００）２７５：１５２００）
　　２）Human β‐defensin‐２（hBD‐２）is an antimicrobial peptide which belongs to one of the most important host defence system against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD‐２ mRNA in MKE４５ gastric mucosal cells. H. pylori, but not culture filtrate, increased hBD‐２mRNAlevel in MKN４５ cells, whereas thus inductive effect of H. pylori was not detected when Intestine４０７ cells were incubated with H. pylori. Among the tested strains of H. pylori, which lacks Cag PAI, did not induce hBD‐２ mRNA in MKN４５ cells. These results suggested that cag PAI of H. pylori is important for inductive expression of hBD‐２ mRNA in MKN４５ cells. Exposure of MKN４５ cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML３５， resulted in remarkable induction of hBD‐２ mRNA.（Ref. Biochem. Biophys. Res. Commun.（１９９９）２８３：７７０，Infect.Immun.（２０００）６８：１８０６）

Studies on the development of cholera vaccine.
　　The overexpression of fimbriae of Vibrio cholerae O１ is uuder study for use in cholera vaccine trial. （Ref. Microbiol. Immunol.（２０００）４４：４３９）