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Research Focus

Host Detection of Inflammatory Microbial Products by the Innate Immune System

My laboratory is focused on understanding the mechanisms by which cells utilize the innate immune system to detect microbes and initiate defensive inflammatory responses. This work has three foci. First, we seek to understand the structural features of the Toll like receptors and their allied proteins LBP, CD14, and MD-2, which enable them to bind with high affinity to microbes and their components. Second, we seek to understand the structural changes by which binding of a microbial ligand to the extracellular domain of the receptor leads to signal transduction across the cell membrane and initiation of intracellular signaling cascades. Third, we seek to understand the involvement of microbial pathogen receptors in several inflammatory diseases including atherosclerosis.

Awards & Professional Activities

Member, Editorial Board, Journal of Biological Chemistry, Journal of Immunology
Member, NIH Study Section, Lung Biology and Pathology

Selected References

Lee,H.K., Lee,J., and Tobias,P.S. 2002. Two Lipoproteins Extracted from Escherichia coli K-12 LCD25 Lipopolysaccharide Are the Major Components Responsible for Toll-Like Receptor 2-Mediated Signaling. J.Immunol. 168:4012-4017.

Viriyakosol,S., Tobias,P.S., Kitchens,R.L., and Kirkland,T.N. 2001. MD-2 binds to bacterial lipopolysaccharide. J.Biol.Chem. 276:38044-38051.

Werts,C., Tapping,R.I., Mathison,J.C., Chuang,T.H., Kravchenko,V., Saint,G., I, Haake,D.A., Godowski,P.J., Hayashi,F., Ozinsky,A. et al. 2001. Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat.Immunol. 2:346-352.

da Silva,C.J., Soldau,K., Christen,U., Tobias,P.S., and Ulevitch,R.J. 2001. Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD14 to TLR4 and MD-2. J.Biol.Chem. 276:21129-21135.