Microbiology

William M. Nauseef, MD

Portrait

Professor of Internal Medicine  - Infectious Diseases
Professor of Microbiology

Contact Information

Email: william-nauseef@uiowa.edu
Web: Inflammation Program
Web: Interdisciplinary Graduate Program in Immunology

Education

BA, Honors, Chemistry, Hamilton College, Clinton, NY
MD, Medicine, cum laude, SUNY Upstate Medical Center, Syracuse, New York

Residency, Medicine, University of Wisconsin
Fellowship, Infectious Diseases, Yale University, New Haven, CT

Licensure and Certifications

Infectious Diseases American Board of Internal Medicine
Internal Medicine American Board of Internal Medicine

Education/Training Program Affiliations

Biosciences Graduate Program
Interdisciplinary Graduate Program in Immunology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

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, Program and Institute Affiliations

Center for Immunology and Immune-based Diseases

Date Last Modified: 06/07/2014 - 21:56:23