Research Topics
Genomes and Genes
| Michael J HoltzmanSummaryAffiliation: Washington University School of Medicine Country: USA Publications
Research Grants
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Detail Information
Publications
Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergensMichael J Holtzman
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, USA
J Clin Invest 122:2741-8. 2012..A particular challenge will be to understand and balance the innate as well as the adaptive immune responses to defend the host against acute infection as well as chronic inflammatory disease...- Host epithelial-viral interactions as cause and cure for asthmaMichael J Holtzman
Drug Discovery Program, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA
Curr Opin Immunol 23:487-94. 2011..We also introduce a rationale for how antiviral performance at the epithelial cell level might be improved to prevent acute infectious illness and chronic inflammatory disease caused by respiratory viruses... - Persistent activation of an innate immune response translates respiratory viral infection into chronic lung diseaseEdy Y Kim
Department of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Nat Med 14:633-40. 2008.... - Immune pathways for translating viral infection into chronic airway diseaseMichael J Holtzman
Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
Adv Immunol 102:245-76. 2009..Together, the findings identify an adaptive immune response that mediates acute disease and an innate immune response that drives chronic inflammatory lung disease in experimental and clinical settings... - Macrophage chitinase 1 stratifies chronic obstructive lung diseaseEugene Agapov
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St Louis, MO 63110, USA
Am J Respir Cell Mol Biol 41:379-84. 2009..The findings provide a means to noninvasively track alternatively activated macrophages in chronic lung disease and thereby better differentiate molecular phenotypes in heterogeneous patient populations... 
Airway epithelial versus immune cell Stat1 function for innate defense against respiratory viral infectionLaurie P Shornick
Department of Biology and Department of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 63103, USA
J Immunol 180:3319-28. 2008..These findings provide some of the most definitive evidence to date for the critical role of barrier epithelial cells in innate immunity to common pathogens, particularly in controlling viral replication...- Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasiaMitchell H Grayson
Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
J Exp Med 204:2759-69. 2007..Therefore, lung DC expression of FcepsilonRIalpha is part of the antiviral response that recruits CD4(+) T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses... - Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cellsBrian T Edelson
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
J Exp Med 207:823-36. 2010..These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs... - Controls for lung dendritic cell maturation and migration during respiratory viral infectionMitchell H Grayson
Division of Allergy and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
J Immunol 179:1438-48. 2007..Our results indicate that pDCs and cDCs respond distinctly to respiratory paramyxoviral infection with patterns of movement that should serve to coordinate the innate and adaptive immune responses, respectively... - CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infectionJeffrey W Tyner
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Nat Med 11:1180-7. 2005..The antiapoptotic action of chemokine signaling may therefore allow scavengers to finally stop the host cell-to-cell infectious process... - Cigarette smoke induces nucleic-acid oxidation in lung fibroblastsGaetan Deslee
Division of Pulmonary and Critical Care Medicine, School of Medicine, Washington University, St Louis, Missouri 63110, USA
Am J Respir Cell Mol Biol 43:576-84. 2010..Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema... - "Hit-and-run" effects of paramyxoviruses as a basis for chronic respiratory diseaseMichael J Holtzman
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
Pediatr Infect Dis J 23:S235-45. 2004..Here we question whether the innate immune system, including airway epithelial cells, and the adaptive one may manifest an aberrant antiviral response as an additional basis for chronic inflammatory diseases, including asthma... - Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illnessKaharu C Sumino
Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
Thorax 65:639-44. 2010..A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers... - Dipeptidyl peptidase I-dependent neutrophil recruitment modulates the inflammatory response to Sendai virus infectionAntonina M Akk
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
J Immunol 180:3535-42. 2008..These results indicate that DPPI and neutrophils play a critical role in Sendai virus-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine response... - Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family membersAnand C Patel
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
Physiol Genomics 25:502-13. 2006.... - IL-13-induced airway mucus production is attenuated by MAPK13 inhibitionYael G Alevy
Drug Discovery Program, Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 122:4555-68. 2012..These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases... - Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signalsJeffrey W Tyner
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 116:309-21. 2006.... - Defining and adjusting divergent host responses to viral infectionMichael J Holtzman
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Immunol Res 32:123-41. 2005.... - Acute and chronic airway responses to viral infection: implications for asthma and chronic obstructive pulmonary diseaseMichael J Holtzman
Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St Louis, MO 63110, USA
Proc Am Thorac Soc 2:132-40. 2005..Identifying specific components of the mucosal immune system that manifest an aberrant antiviral response may thereby allow for adjusting this response to improve acute and chronic outcomes after viral infection... - A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cellsYong Zhang
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110 1093, USA
Am J Respir Cell Mol Biol 36:515-9. 2007..It should prove extremely useful for defining ciliated cell function in airway mucosal immunity as well as development and reproduction... - Melanoma differentiation-associated gene 5 (MDA5) is involved in the innate immune response to Paramyxoviridae infection in vivoLeonid Gitlin
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS Pathog 6:e1000734. 2010.... - Emerging role of dendritic cells in respiratory viral infectionMitchell H Grayson
Department of Internal Medicine, Washington University School of Medicine, Campus Box 8122, 660 South Euclid Avenue, Saint Louis, MO 63110, USA
J Mol Med (Berl) 85:1057-68. 2007..Finally, we identify potential targets for future therapeutic strategies to ameliorate disease caused by respiratory virus infection... - New immune pathways from chronic post-viral lung diseaseLoralyn A Benoit
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
Ann N Y Acad Sci 1183:195-210. 2010..These findings extend our understanding of the complex mechanisms that underlie chronic obstructive lung disease and provide useful targets for diagnosis and therapy of this common disorder... - Viral induction of a chronic asthma phenotype and genetic segregation from the acute responseMichael J Walter
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 110:165-75. 2002..These two phenotypes can be segregated by their dependence on the ICAM-1 gene and so depend on distinct controls that appear critical for the development of lifelong airway diseases such as asthma... - Monitoring in vivo changes in lung microstructure with ³He MRI in Sendai virus-infected miceWei Wang
Department of Physics, Washington Univ Box 8131, Dept of Radiology, 510 S Kingshighway, St Louis, MO 63110, USA
J Appl Physiol 112:1593-9. 2012..Our results indicate that (3)He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and that the Sendai mouse model has the potential to be a valid murine model of COPD... 
The role of CLCA proteins in inflammatory airway diseaseAnand C Patel
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
Annu Rev Physiol 71:425-49. 2009....- Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cellsAida Ibricevic
Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
J Virol 80:7469-80. 2006.... - Genetic variability of human metapneumovirus infection: evidence of a shift in viral genotype without a change in illnessEugene Agapov
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
J Infect Dis 193:396-403. 2006..These findings suggest that hMPV may vary in genetic structure, to allow for a seasonal shift in predominant genotype and the maintenance of infection rates... - Alternatively activated macrophages and airway diseaseDerek E Byers
Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Chest 140:768-74. 2011..Here, we review basic and clinical research studies that highlight the importance of AAMs in the pathogenesis of asthma, COPD, and other chronic airway diseases... - Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activationZeynep Yurtsever
Biochemistry Program, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 287:42138-49. 2012..These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface... - Apoptosis in the airways: another balancing act in the epithelial programJeffrey W Tyner
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Am J Respir Cell Mol Biol 29:3-7. 2003 - Developing the epithelial, viral, and allergic paradigm for asthma: Giles F. Filley lectureMichael J Holtzman
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Chest 123:377S-84S. 2003 - High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next-generation antiviral drug discoveryDhara A Patel
Drug Discovery Program, Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America
PLoS ONE 7:e36594. 2012.... - Oxidative damage to nucleic acids in severe emphysemaGaetan Deslee
Washington University School of Medicine, Division of Pulmonary and Critical Care Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Chest 135:965-74. 2009..Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs... - Epithelial cell proliferation contributes to airway remodeling in severe asthmaLance Cohen
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St Louis, MO 63110 1093, USA
Am J Respir Crit Care Med 176:138-45. 2007..Despite long-term therapy with corticosteroids, patients with severe asthma develop irreversible airway obstruction... - Immunogenetic programs for viral induction of mucous cell metaplasiaMichael J Holtzman
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Am J Respir Cell Mol Biol 35:29-39. 2006 - Antigen-nonspecific recruitment of Th2 cells to the lung as a mechanism for viral infection-induced allergic asthmaRobin Stephens
Center for Immunology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
J Immunol 169:5458-67. 2002..This implies that circulating Th2 cells in allergic individuals could enter the lungs in response to infection or inflammation and become activated to trigger allergy... - Chemokine signaling regulates apoptosis as well as immune cell traffic in host defenseMitchell H Grayson
Department of Medicine and Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri, USA
Cell Cycle 5:380-3. 2006..In addition, we introduce new work to support the more traditional role of CCL5 in mediating adaptive immune cell traffic and activation in this same setting... - Cutting edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammationChristine Deppong
Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
J Immunol 176:3909-13. 2006..Thus, these receptors are critical determinants of the duration of allergic airway inflammation... - Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airwayMario Castro
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110 1093, USA
Am J Respir Crit Care Med 169:842-9. 2004.... - Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of lifeKaharu Sumino
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
J Allergy Clin Immunol 129:1267-1273.e1. 2012..However, the determinants of susceptibility to acute respiratory tract infections still need to be defined... - Intravital microscopy comparing T lymphocyte trafficking to the spleen and the mesenteric lymph nodeMitchell H Grayson
Division of Allergy and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Am J Physiol Heart Circ Physiol 284:H2213-26. 2003.... - Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessmentKaharu C Sumino
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Infect Dis 192:1052-60. 2005.... - Modification of the Stat1 SH2 domain broadly improves interferon efficacy in proportion to p300/CREB-binding protein coactivator recruitmentYong Zhang
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Biol Chem 280:34306-15. 2005..Thus, SH2 domain determinants may be modified to direct better Stat1 phosphorylation, DNA binding, and coactivator recruitment to fully improve IFN efficacy... - Drug development for asthmaMichael J Holtzman
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St Louis, MO 63110, USA
Am J Respir Cell Mol Biol 29:163-71. 2003..Each of these considerations may provide an alternative strategy for further drug development for asthma and other complex diseases... - A centennial history of research on asthma pathogenesisMichael J Walter
Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Am J Respir Cell Mol Biol 32:483-9. 2005 - Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha/beta interferon responsivenessMindy S Lo
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110, USA
J Virol 79:9315-9. 2005..RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion... - Immunity, inflammation, and remodeling in the airway epithelial barrier: epithelial-viral-allergic paradigmMichael J Holtzman
Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
Physiol Rev 82:19-46. 2002.... - Molecular heterogeneity in the choroid plexus epithelium: the 22-member γ-protocadherin family is differentially expressed, apically localized, and implicated in CSF regulationMark A Lobas
Department of Biology, The University of Iowa, Iowa City, Iowa, USA
J Neurochem 120:913-27. 2012..Together, these results suggest an unsuspected role for the γ-Pcdhs in CSF production and demonstrate a surprising molecular heterogeneity in the CP epithelium...
Research Grants
- BASIS OF CHRONIC MUCOUS CELL METAPLASIAMichael J Holtzman; Fiscal Year: 2010..Our work will thereby provide new therapeutic strategies to restore normal lung architecture and correct mucus production to a level that is helpful rather than harmful for lung function. ..