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
Lauren Kinkead, Graduate student Department of Microbiology
Stephanie Silva Del-Toro, Graduate student
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
Interdisciplinary Graduate Training Program in Immunology
Center for Immunology and Immune-Based Diseases
Society for Leukocyte Biology (SLB)
American Society for Microbiology(ASM)
American Association of Immunologists (AAI)
New York Academy of Sciences (NYAS)
American Association for the Advancement of Science (AAAS)
International Innate Immunity and Endotoxin Society (IEIIS)
International Tularemia Society (TULISOC)
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.
McCracken, J.M., L.C. Kinkead, R.L. McCaffrey, and L.-A.H. Allen. 2016. Francisella tularensis modulates a distinct set of regulatory factors and sustains mitochondrial integrity to impair human neutrophil apoptosis. J. Innate Immun. 8:(in press 01-09-16). PMCID in process.
Leung, A., N.S. Gregory, L.-A.H. Allen, and K. Sluka. 2016. Regular physical activity prevents chronic pain by altering resident macrophage phenotype and increasing IL-10 in mice. Pain. 157:70-79. PMC4685958.
Allen, L.-A.H. Microbicidal Mechanisms. In: Ralph A. Bradshaw and Philip D. Stahl (Editors in Chief), Encyclopedia of Cell Biology, Vol. 2, Academic Press, Waltham, MA, 2016, pp. 766-775.
Rasmussen, J., JR Fletcher, M Long, L-A.H. Allen, and BD Jones. 2015. Characterization of Francisella tularensis Schu S4 mutants identified from a transposon library screened for O-antigen and capsule deficiencies. Front. Microbiol. 6:388. PMCID: PMC4419852.
Bandyopadhyay, S., M.E. Long and L.-A.H. Allen. 2014. Differential expression of microRNAs in Francisella tularensis-infected human macrophages: miR-155-dependent downregulation of MyD88 inhibits the inflammatory response. PLoS ONE 9(10):e109525. PMC4190180.
Dassie, J., L. Hernandez, G. Thomas, M.E. Long, W. Rockey, C. Howell, Y. Chen, F. Hernandez, X.Y. Liu, M.E. Wilson, L.-A.H. Allen, D. Vaena, D. Myerholtz and P. Giangrande. 2014.Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate specific membrane antigen (PSMA). Mol. Ther. 22:1910-1922. PMC4429728.
McCracken, J.M. and L.-A.H. Allen. 2014. Regulation of human neutrophil apoptosis and lifespan in health and disease. J. Cell Death. 7:15-23. PMC4167320.
Allen, L.-A.H. 2014. Immunofluorescence and confocal microscopy of neutrophils. Methods Mol. Biol. 1124:251-268. PMC4459639.
Allen, L.-A.H. 2013. Neutrophils: potential therapeutic targets in tularemia? Front. Cell Infect. Microbiol. 3:109. PMC3873502.
Faron, M., J.A. Fletcher, J.R. Rasmussen, M.E. Long, L.-A.H. Allen and B.D. Jones. 2013. The Francisella tularensis migR, trmE and cphA genes contribute to FPI gene regulation and intracellular growth by modulation of the stress alarmone ppGpp. Infect. Immun. 81:2800-2811 PMC3719569.
Allen, L.-A.H. 2013. Editorial: Leukocytes in tularemia – so many cells, so little time. J. Leukoc. Biol. 93:641-643. PMC3629439.
Long, M.E., S.R. Lindemann, J.A. Rasmussen, B.D. Jones and L.-A.H. Allen. 2013. Disruption of Francisella tularensis Schu S4 iglI, iglJ and pdpC results in attenuation for growth in human macrophages and in vivo in mice, and reveals a unique phenotype for pdpC. Infect. Immun. 81:850-861. Epub on-line Dec. 28, 2012. PMC3584877.
Schwartz, J.T., S. Bandyopadhyay, S.D. Kobayashi, J. McCracken, A.R. Whitney, F.R. DeLeo, and L.-A.H. Allen. 2013. Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis. J. Innate Immun. 5:5124-5136 (published on-line 9-14-12). PMC3703778.
Schwartz, J.T., J.H. Barker, M.E. Long, J. Kaufman, J. McCracken, and L.-A.H. Allen. 2012. Natural IgM mediates complement-dependent uptake of Francisella tularensis by human neutrophils via Complement Receptors 1 and 3 in nonimmune serum. J. Immunol. 189:3064-3077. PMC3436988.
Casbon, A.J., M.E. Long, K.W. Dunn, L.-A.H. Allen and M.C. Dinauer. 2012. Effects of IFNg on intracellular trafficking of macrophage NADPH oxidase flavocytochrome b558. J. Leukoc. Biol. 92:869-882. (Cover article). PMC3441311.
Schwartz, J.T., J.H. Barker, J. Kaufman, D.C. Fayram, J.M. McCracken and L.-A.H. Allen. 2012. Francisella tularensis inhibits the intrinsic and extrinsic pathways to delay constitutive apoptosis and prolong human neutrophil lifespan. J. Immunol. 188:3351-3363. (featured “In this issue” JI 188:2927). PMC3311780.
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.
Rodriguez, N.E., U. Guar-Dixit, L.-A.H. Allen, and M.E. Wilson. 2011. Stage-specific pathways of Leishmania infantum chagasi entry and phagosome maturation in macrophages. PLoS One, 6(4):e19000.
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. 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. PMC2974429.