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Professor of Internal Medicine
- Infectious DiseasesProfessor of
Email: email@example.comWeb: Inflammation ProgramWeb: Interdisciplinary Graduate Program in Immunology
BA, Honors, Chemistry, Hamilton College, Clinton, NYMD, Medicine, cum laude, SUNY Upstate Medical Center, Syracuse, New York
Residency, Medicine, University of WisconsinFellowship, Infectious Diseases, Yale University, New Haven, CT
Infectious Diseases, American Board of Internal MedicineInternal Medicine, American Board of Internal Medicine
Biosciences Graduate ProgramInterdisciplinary Graduate Program in ImmunologyInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program
Ongoing projects in the laboratory are designed to address several questions pertinent to the cell biology of neutrophil-mediated responses during inflammation and host response to infection. We have a longstanding interest in two important aspects of the neutrophil response, namely the NADPH-dependent oxidase and the granule hemeprotein myeloperoxidase (MPO), and have active projects examining various aspects of each of these important elements of the acute inflammation. Studies on the NADPH-dependent oxidase are directed at two major questions. First, how does lipopolysaccharide, a component of most gram-negative bacteria, include the neutrophil to become ""primed"" for subsequent activation? Detailed analysis of the subcellular localization of p47phox and p67phox and the phosphorylation state of p47phox exposure to lipopolysaccharide are under study. Second, we are examining the role of the membrane-associated cytoskeleton in regulating and/or directing assembly of the NADPH-dependent oxidase. Current attention is focused on p57, a 57-kDa homologue of the protein coronin found in Dictyostelium, and its association with oxidase components and its recruitment to the nascent phagosome. As part of these studies, we are identifying and characterizing other membrane proteins in human neutrophils which bind F-actin, either constitutively or after activation.
Studies related to our interest in MPO include characterization of MPO biosynthesis and the identification of various genotypes of hereditary MPO deficiency. Studies on MPO biosynthesis include characterization of the role of molecular chaperone calreticulin and calnexin in the early steps of MPO processing as well as assessment of the various ""quality control"" mechanisms operating in the endoplasmic reticulum of myeloid precursors. Using a random peptide bacteriophage display library, we are searching for peptide motifs recognized by calreticulin and calnexin in their roles as chaperones. In addition, studies are ongoing to define the mechanism by which heme is incorporated into MPO. The impact of heme nsertion on the subsequent proteolytic processing and intracellular targeting of MPO to the lysosome is also under study. Lastly, studies of hereditary MPO deficiency include identification of the genotype underlying the specific phenotype and then characterization of the impact of that mutation on the synthesis of MPO. For these studies we used transfected K562 cells to express mutant MPO cDNA and characterize the biosynthesis. Our findings from such analysis complement well those derived from studies of MPO biosynthesis in established myeloid cell lines.
Center for Immunology and Immune-based Diseases
Date Last Modified: 07/31/2013 -
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