17 results match your criteria: "University of Wisconsin-Madison School of Medicine and Public Health (SMPH)[Affiliation]"
Front Immunol
July 2024
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Front Immunol
April 2024
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, United States.
Introduction: The human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic lung diseases. In immune competent hosts, RSV productively infects highly differentiated epithelial cells, where it elicits robust anti-viral, cytokine and remodeling programs. By contrast, basal cells are relatively resistant to RSV infection, in part, because of constitutive expression of an intrinsic innate immune response (IIR) consisting of a subgroup of interferon (IFN) responsive genes.
View Article and Find Full Text PDFJ Am Geriatr Soc
March 2024
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, Wisconsin, USA.
Background: Despite research demonstrating the risks of using feeding tubes in persons with advanced dementia, they continue to be placed. The natural history of dysphagia among patients with advanced dementia has not been examined. We conducted a secondary analysis of a national cohort of persons with advanced dementia staying at a nursing home stay before hospitalization to examine (1) pre-hospitalization dysphagia prevalence and (2) risk of feeding tube placement during hospitalization based on preexisting dysphagia.
View Article and Find Full Text PDFFront Immunol
August 2023
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States.
Recent advances have uncovered the non-random distribution of 7, 8-dihydro-8-oxoguanine (8-oxoGua) induced by reactive oxygen species, which is believed to have epigenetic effects. Its cognate repair protein, 8-oxoguanine DNA glycosylase 1 (OGG1), reads oxidative substrates and participates in transcriptional initiation. When redox signaling is activated in small airway epithelial cells, the DNA repair function of OGG1 is repurposed to transmit acute inflammatory signals accompanied by cell state transitions and modification of the extracellular matrix.
View Article and Find Full Text PDFFront Immunol
August 2023
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, United States.
Introduction: The unfolded protein response (UPR) has emerged as an important signaling pathway mediating anti-viral defenses to Respiratory Syncytial Virus (RSV) infection. Earlier we found that RSV replication predominantly activates the evolutionarily conserved Inositol Requiring Enzyme 1α (IRE1α)-X-Box Binding Protein 1 spliced (XBP1s) arm of the Unfolded Protein Response (UPR) producing inflammation, metabolic adaptation and cellular plasticity, yet the mechanisms how the UPR potentiates inflammation are not well understood.
Methods: To understand this process better, we examined the genomic response integrating RNA-seq and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) analyses.
J Am Med Dir Assoc
September 2023
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, USA; Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Electronic address:
Nucleic Acids Res
May 2023
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI 53705, USA.
Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. Recently we observed the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)-X-box-binding protein 1 spliced (XBP1s) axis, enhancing glucose shunting to protein N glycosylation. To better understand the genomic targets of XBP1s, we identified its genomic targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1s in RSV infection.
View Article and Find Full Text PDFNucleic Acids Res
February 2023
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Reactive oxygen species (ROS) are implicated in epithelial cell-state transition and deposition of extracellular matrix upon airway injury. Of the many cellular targets of ROS, oxidative DNA modification is a major driving signal. However, the role of oxidative DNA damage in modulation profibrotic processes has not been fully delineated.
View Article and Find Full Text PDFClin Proteomics
May 2022
Institute for Clinical and Translational Research (ICTR), University of Wisconsin-Madison, 715 Highland Ave, Madison, WI, 53705, USA.
Background: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway.
View Article and Find Full Text PDFFront Pharmacol
December 2021
Department of Internal Medicine, University of Texas Medical Branch Galveston, Galveston, TX, United States.
Disruption of the lower airway epithelial barrier plays a major role in the initiation and progression of chronic lung disease. Here, repetitive environmental insults produced by viral and allergens triggers metabolic adaptations, epithelial-mesenchymal plasticity (EMP) and airway remodeling. Epithelial plasticity disrupts epithelial barrier function, stimulates release of fibroblastic growth factors, and remodels the extracellular matrix (ECM).
View Article and Find Full Text PDFFront Mol Biosci
October 2021
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, United States.
Bromodomain-containing protein 4 plays a central role in coordinating the complex epigenetic component of the innate immune response. Previous studies implicated BRD4 as a component of a chromatin-modifying complex that is dynamically recruited to a network of protective cytokines by binding activated transcription factors, polymerases, and histones to trigger their rapid expression via transcriptional elongation. Our previous study extended our understanding of the airway epithelial BRD4 interactome by identifying over 100 functionally important coactivators and transcription factors, whose association is induced by respiratory syncytial virus (RSV) infection.
View Article and Find Full Text PDFExpert Rev Proteomics
May 2021
Department of Internal Medicine and Institute for Clinical and Translational Research (ICTR), University of Wisconsin-Madison, Madison, WI, USA.
: Respiratory syncytial virus (RSV) is a major human pathogen associated with long term morbidity. RSV replication occurs primarily in the epithelium, producing a complex cellular response associated with acute inflammation and long-lived changes in pulmonary function and allergic disease. Proteomics approaches provide important insights into post-transcriptional regulatory processes including alterations in cellular complexes regulating the coordinated innate response and epigenome.
View Article and Find Full Text PDFViruses
March 2021
Institute for Clinical and Translational Research (ICTR), University of Wisconsin-Madison, Madison, WI 53705, USA.
Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-κB transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain-containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators.
View Article and Find Full Text PDFFront Immunol
September 2021
Department of Internal Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, United States.
Epigenetics plays an important role in the priming the dynamic response of airway epithelial cells to infectious and environmental stressors. Here, we examine the epigenetic role of the SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin A4 (SMARCA4) in the epithelial response to RSV infection. Depletion of SMARCA4 destabilized the abundance of the SMARCE1/ARID1A SWI/SNF subunits, disrupting the innate response and triggering a hybrid epithelial/mesenchymal (E/M) state.
View Article and Find Full Text PDFViruses
January 2021
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI 53705, USA.
The innate immune response (IIR) involves rapid genomic expression of protective interferons (IFNs) and inflammatory cytokines triggered by intracellular viral replication. Although the transcriptional control of the innate pathway is known in substantial detail, little is understood about the complexity of alternative splicing (AS) and alternative polyadenylation (APA) of mRNAs underlying the cellular IIR. In this study, we applied single-molecule, real-time (SMRT) sequencing with mRNA quantitation using short-read mRNA sequencing to characterize changes in mRNA processing in the epithelial response to respiratory syncytial virus (RSV) replication.
View Article and Find Full Text PDFFront Pharmacol
December 2020
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI, United States.
Idiopathic Pulmonary Fibrosis (IPF) is a chronically progressive interstitial lung that affects over 3 M people worldwide and rising in incidence. With a median survival of 2-3 years, IPF is consequently associated with high morbidity, mortality, and healthcare burden. Although two antifibrotic therapies, pirfenidone and nintedanib, are approved for human use, these agents reduce the rate of decline of pulmonary function but are not curative and do not reverse established fibrosis.
View Article and Find Full Text PDFViruses
July 2020
Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health (SMPH), Madison, WI 53705, USA.
Lower respiratory tract infection (LRTI) with respiratory syncytial virus (RSV) is associated with reduced lung function through unclear mechanisms. In this study, we test the hypothesis that RSV infection induces genomic reprogramming of extracellular matrix remodeling pathways. For this purpose, we sought to identify transcriptionally active open chromatin domains using assay for transposase-accessible-next generation sequencing (ATAC-Seq) in highly differentiated lower airway epithelial cells.
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