Welcome to the Iowa Inflammation Program
1972 - B.A., Chemistry, Hamilton College, Clinton, NY
1976 - M.D., Medicine, SUNY- Upstate Medical Center
1977-79 - Resident, Department of Medicine, University of Wisconsin
1979-83 - Fellow, Infectious Diseases, Yale University
Mallary C. Wacker, PhD
Sara Hinde RA II
Kevin Leidal RA III
Sally McCormick-Hill RAII
Sarah Bloomberg, RA I
Department of Internal Medicine
Department of Microbiology
Department of Internal Medicine, Division of Infectious Diseases
Immunology Graduate Program
Interdisciplinary Graduate Training Program in Molecular and Cellular Biology
Medical Scientist Training Program
Infectious Diseases Society of America
American Society of Microbiology
American Society of Hematology
American Society for Cell Biology
American Society for Clinical Investigation
Association of American Physicians
Society for Leukocyte Biology
American Society for Biochemistry and Molecular Biology
American Association for Advancement of Science (AAAS)
Ongoing projects in the laboratory address several questions pertinent to the cell biology of neutrophil-mediated responses during inflammation and host response to infection. As the dominant cellular component in “pus”, neutrophils respond immediately to infectious challenges and serve as the sentinel of the inflammatory response. 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 acute inflammation. Studies on the NADPH-dependent oxidase are directed at understanding the molecular basis for the temporal and spatial control of oxidant production in the phagosome, the subcellular compartment in which the ingested microbe is trapped. More recently our studies have extended to include the cell biology of related NADPH oxidase systems in non phagocytic cells, where oxidant generation serves purposes other than host defense. Studies related to our interest in MPO include characterization of MPO biosynthesis and the identification of various genotypes of inherited MPO deficiency. Studies on MPO biosynthesis include characterization of the role of molecular chaperones 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. In addition, studies are ongoing to define the mechanism by which heme is incorporated into MPO. The impact of heme insertion on the subsequent proteolytic processing and intracellular targeting of MPO to the lysosome is also under study. Studies of hereditary MPO deficiency also 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 HEK 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. Lastly, these two lines of investigation converge in our ongoing work on how neutrophils kill staphylococci and how the recently emerging community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) survives within neutrophils. CA-MRSA have become an enormous clinical problem in the community in the past 5-7 years, and the biologic basis for the organism’s enhanced virulence is not understood, but likely linked to it ability to endure, evade, and subvert neutrophil killing.
Lorentzen D, Durairaj L, Pezzulo AA, Nakano Y, Launspach J, Stoltz DA, Zamba G, McCray PB Jr, Zabner J, Welsh MJ, Nauseef WM, Bánfi B. Concentration of the antibacterial precursor thiocyanate in cystic fibrosis airway secretions. Free Radic Biol Med. 2011 Feb 17. [Epub ahead of print] PMID: 21334431
Metzler, K.D., Fuchs, T.A., Nauseef, W.M., Reumaux, D., Rosier, J., Schulze, I., Wahn, V., Papayannopoulos, V., Zychlinsky, A. Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood, 2010 (ahead of print)
Pang, Y.Y., Schwartz, J., Thoendel, M., Ackermann, L.W., Horswill, A.R., Nauseef, W.M. agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils. J. Innate Immun. 2(6):546-59, 2010.
Ulland, T.K., Buchan, B.W., Ketterer, M.R., Fernandes-Alnemri, T., Meyerholz, D.K., Apicella, M.A., Ainemri,E.S., Jones, B.D., Nauseef, W.M., Sutterwala, F.S. Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in meleanoma 2 inflammasome activation and a loss of virulence. J. Immunol. 185(5):2670-4, 2010.
Quinn, M.T., DeLeo, F.R., Nauseef, W.M. Memorial: Gary Michael Bokoch, 1954-2010. J. Leukoc Biol. 87(4)535-6, 2010.
Painter, R.G., Marrero, L., Lombard,G.A., Valentine, V.G., Nauseef, W.M., Wang, G. CFTR-mediated halide transport in phagosomes of human neutrophils. J.Leukoc.Biol. 87:933-42, 2010.
Matute, J.D., Arias,A.A., Wright, N.A.M., Wrobel, I., Waterhouse, C.C.M., Li, X.J., Marchal, C.C., Stull, N.D., Lewis, D.B., Steel, M., Kellner, J.D., Yu, W., Meroueh, S.O., Nauseef, W.M., Dinauer, M.C. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood, 114:3309-15, 2009.
Schwartz, J., Leidal, K.G., Femling, J.K., Weiss, J.P., Nauseef, W.M. Neutrophil bleaching of GFP-expressing staphylococci: probing the intraphagosomal fate of individual bacteria. J. Immunol. 183:2632-41, 2009.