Welcome to the Iowa Inflammation Program
1982 - B.S., Biochemistry, University of California,
1983 - M.S., Biochemistry - University of California
1990 - Ph.D., Biochemistry - University of Wisconsin
1991-1995 - Postdoctoral Fellowship, Immunology/ Cell Biology, Rockefeller University
Brandi Ketelson, Research Assistant
Jenna McCracken, MSTP student Dept of Microbiology
Lauren Kinkead, Graduate student Department of Microbiology
Laura Whitmore, Post Doctoral Fellow
Department of Internal Medicine
Division of Infectious Diseases,
Medical Scientist Training Program
Interdisciplinary Graduate Training Program in Molecular and Cellular Biology
Department of Microbiology
Research in my laboratory studies mechanisms of pathogenesis of two Gram-negative bacteria, Francisella tularensis and Helicobacter pylori.
Helicobacter pylori colonizes the gastric epithelium of up to half the world’s population and plays a causative role in the development of peptic ulcers and gastric cancer. One hallmark of H. pylori is its persistence. H. pylori infection causes a massive influx of neutrophils (PMNs) and mononuclear cells into the gastric mucosa, chronic gastritis and damage to host tissue, but the immune response does not resolve the infection and the reasons for this host-defense defect are unclear. Our long-term goal is to determine at the molecular level how H. pylori avoids being killed by the host innate immune system with a particular focus on bacteria-phagocyte interactions. At the present time our research on this topic can be divided into three main areas. 1) Identification of H. pylori virulence genes important for bacterial survival inside phagocytes. 2) Characterization of the mechanism(s) by which H. pylori activates neutrophils and disrupts granule targeting. 3) Defining the fate of infected neutrophils and intracellular bacteria.
F. tularensis is a facultative intracellular pathogen that infects several cell types including macrophages and neutrophils. Interest in this organism has increased in recent years because of its potential use as a bioweapon. After entry into host cells, F. tularensis escapes the phagosome and replicates in the cytosol, but how this is achieved is only partially understood. Thus far, we have identified receptors used for bacterial uptake, demonstrated that this organism uses multiple mechanisms to disrupt NADPH oxidase activity and evade killing by toxic reactive oxygen species, identified bacterial genes required for this process, including the regulator MigR that is also required for phagosome escape and intracellular growth. We demonstrated using mutants deficient in capsule and LPS O-antigen synthesis that these surface sugars play a more complex role in virulence than was previously appreciated, as the mutants induce rapid macrophage death whereas wild-type organisms do not. Neutrophils are very short lived cells, and in our most recent work we demonstrated that lifespan of these cells is profoundly prolonged. Current areas of study include: 1) Characterization of additional capsule and O-antigen mutants. 2) Determining the mechanisms NADPH oxidase inhibition. 3) Characterizing of the mechanisms by which neutrophil apoptosis is impaired via studies of host cell gene expression and signaling and identification of relevant bacterial factors and genes. An additional goal is to begin to examine the phenotypes of cells infected by F. tularensis in vivo.
Schwartz, J.T., Jason H. Barker, Justin Kaufman, Drew C. Fayram, Jenna M. McCracken and L.-A.H. Allen. 2012. Francisella tularensis inhibits the intrinsic and extrinsic pathways to inhibit apoptosis and prolong human neutrophil lifespan. J. Immunol. 188: avail on-line Feb. 22nd, print copy April 1.
Cambronero, J.G., L.-A.H. Allen, M.K. Cathcart, L.B. Justement, E.J. Kovacs, K.R. McLeish, and W.M. Nauseef. 2012. Writing a first grant proposal. Nat. Immunol. 13:105-108.
Lindemann, S.R., K. Peng, M.E. Long, J.R. Hunt, M.A. Apicella, D.M. Monack, L.-A.H. Allen and B.D. Jones. 2011 F. tularensis mutants in O-antigen and capsule biosynthesis genes induce early cell death in human macrophages. Infect. Immun. 79:581-594. PMCID: PMC3028865.
McCaffrey, R.L., J.T. Schwartz, S.R. Lindemann, J.G. Moreland, B.W. Buchan, B.D. Jones and L.-A.H. Allen. 2010. Multiple mechanisms of NADPH oxidase inhibition by Type A and Type B Francisella tularensis. J. Leukoc. Biol. 88:791-805. PMCID: PMC20617096.
Barker, J. H., R. L. McCaffrey, N. K. Baman, L. A. Allen, J. P. Weiss, and W. M. Nauseef. 2009. The role of complement opsonization in interactions between F. tularensis subsp. novicida and human neutrophils. Microbes Infect 11:762-769.
Casbon, A. -J., L.-A.H. Allen, K.W. Dunn, and M.C. Dinauer. Macrophage NADPH oxidase flavocytochrome b localized to the plasma membrane and Rab11-positive recycling endosomes J. Immunol 182:2325-2339 2009 PMCID: PMC2666390 (avail. 1010/02/15).
Buchan BW, R.L. McCaffrey, S.R. Lindemann, L.-A.H. Allen, and B.D. Jones. 2009 Identification of migR, a regulatory element of the Francisella tularensis live vaccine strain iglABCD virulence operon required for normal replication and trafficking in macrophages. Infect Immun. Jun;77(6):2517-2529. PMCID: PMC2687360 (avail. 2009/12/01).
Schulert, G.S., R.L. McCaffrey, B.W. Buchan, S.R. Lindemann, B.D. Jones, and L.-A.H. Allen. 2009. Francisella tulerensis genes required for inhibition of neutrophil activation and intramacrophage growth identified by random transposon mutagenisis of LVS. Infect. Immun. 77:1324-1336 PMCID: PMC 2663180 (avail. 2009/10/01).
Allen. L.-A.H. 2008. Phagocytosis of Helicobacter pylori. Methods Mol. Biol. 431:147-157.
Allen, L.-A.H. and R.L. McCaffrey. 2007. To activate or not to activate: distinct strategies used by Helicobacter pylori and Francisella tularensis to modulate the NADPH oxidase and survive in human neutrophils. Immunol. Rev. 219:103-117.
Allen, L.-A.H. 2007. Phagocytosis and persistence of Helicobacter pylori. Cell Microbiol. 2007 Apr;9(4):817-28. Epub 2007 Mar 8. Review.
Allen, L.-A.H. 2007. Immunofluorescence and confocal microscopy of neutrophils. Methods Mol Biol. 2007;412:273-87.
McCaffrey, R.L. and L.-A.H. Allen. 2006. Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. J. Leukoc. Biol. 80:1224-1230.
Schulert, G.S. and L.-A.H. Allen 2006. Differential infection of mononuclear phagocytes by Francisella tularensis: role of the macrophage mannose receptor. J. Leukoc. Biol. 80:563-571.
McLendon, M.K., M.A. Apicella, and L.-A.H. Allen. 2006. Francisella tularensis: taxonomy, genetics and immunopathogenesis of a potential agent of biowarfare. Annu. Rev. Microbiol. 60:167-185.
Schwartz, J.T. and L-A.H. Allen, 2005, Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J. Leukoc. Biol. 79:1214-1225.
Allen, L.-A.H., J.A. Allgood, X. Han, and L.M. Wittine. 2005. Phosphoinositide 3-kinase regulates actin polymerization during delayed phagocytosis of Helicobacter pylori. J. Leukoc. Biol. 78:220,230.
Allen, L.-A.H., B.R. Beecher, J.T. Lynch, O.V. Rohner and L.M. Wittine. 2005. Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J. Immunol. 174:3658-3667.
See complete publications list at PubMed