A5060011923- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Phagocytosis and Immune Regulation
- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Histiocytic Disorders and Treatments
- Immune cells in cancer
- Occupational and environmental lung diseases
- IL-33, ST2, and ILC Pathways
- Caveolin-1 and cellular processes
- Occupational exposure and asthma
- Extracellular vesicles in disease
- Chemokine receptors and signaling
- Lung Cancer Treatments and Mutations
- Systemic Sclerosis and Related Diseases
- Microbial metabolism and enzyme function
- NF-κB Signaling Pathways
- Oral and Maxillofacial Pathology
- Cytokine Signaling Pathways and Interactions
- Polyomavirus and related diseases
- Macrophage Migration Inhibitory Factor
- Eosinophilic Disorders and Syndromes
Cedars-Sinai Medical Center
2016-2025
Lung Institute
2016-2025
Howard Hughes Medical Institute
2017
National Institutes of Health
2017
United States Congress
2017
Universidade Nova de Lisboa
2017
University of Lisbon
2017
Instituto Português de Oncologia Francisco Gentil
2017
Nova Medical (United States)
2017
University of Michigan
2005-2014
Although cellular senescence may be a protective mechanism in modulating proliferative capacity, fibroblast is now recognized as key pathogenic idiopathic pulmonary fibrosis (IPF). In aged mice, abundance and persistence of apoptosis-resistant senescent fibroblasts play central role nonresolving lung after bleomycin challenge. Therefore, we investigated whether quercetin can restore the susceptibility IPF to proapoptotic stimuli mitigate bleomycin-induced mice. Unlike normal fibroblasts,...
Idiopathic pulmonary fibrosis is characterized by diffuse alveolar damage and severe fibrosis, resulting in a steady worsening of lung function gas exchange. Because idiopathic generally progressive disorder with highly heterogeneous disease progression, we classified affected patients as either rapid or slow progressors over the first year follow-up then identified differences between two groups to investigate mechanism governing progression. Previous work from our laboratory has...
Background Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but molecular basis for varying rates is poorly understood. The aim present study was to ascertain whether miRNA expression might provide one explanation rapidly versus slowly progressing forms IPF. Methodology and Principal Findings mRNA were isolated surgical lung biopsies IPF patients with a clinically documented rapid or slow course disease over first year after diagnosis. A quantitative...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unremitting extracellular matrix deposition, leading to distortion of architecture and impaired gas exchange. Fibroblasts from IPF patients acquire an invasive phenotype that essential for fibrosis. Here, we performed RNA sequencing analysis on noninvasive fibroblasts found the immune checkpoint ligand CD274 (also known as PD-L1) was upregulated lung required fibroblasts, regulated by p53 FAK, drives in humanized model mice....
The gastrointestinal microbiota influences immune function throughout the body. gut-lung axis refers to concept that alterations of gut commensal microorganisms can have a distant effect on in lung. Overgrowth intestinal Candida albicans has been previously observed exacerbate allergic airways disease mice, but whether subtler changes fungal affect is less clear. In this study we investigated effects population expansion fungus Wallemia mellicola without overgrowth total community. spp. are...
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein kinase 3), and Axl (anexelekto) expression activity are increased IPF.To determine if targeting these pathways would inhibit fibroblast activation the development of fibrosis.Quantitative genomic, proteomic, functional analyses were used to Gas6/TAM (Tyro3,...
The chronic progressive decline in lung function observed idiopathic pulmonary fibrosis (IPF) appears to result from persistent nonresolving injury the epithelium, impaired restitution of epithelial barrier lung, and enhanced fibroblast activation. Thus, understanding these key mechanisms pathways modulating both is essential greater IPF pathogenesis. We examined association VEGF with disease state preclinical models vivo vitro. Tissue circulating levels were significantly reduced patients...
Rationale: The role of the innate immune system in idiopathic pulmonary fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, as well mediate responses against pathogens. Aberrant macrophage activity has been described patients with post-acute sequelae COVID (PASC-F), caveolin scaffolding domain (CSD) peptides have found attenuate inflammation mouse lung injury models. Therefore, we examined, for first time,...
Viruses use Tyro3, Axl, and Mertk (TAM) receptor tyrosine kinases to infect modulate the immune properties of various cell types, which led us investigate whether TAM activation affected primary viral infection exacerbation asthma in experimental models. In these lung-specific models, we observed that Axl was most abundantly induced protein. During respiratory syncytial virus (RSV) infection, anti-Axl mAb treatment significantly increased number IFN-γ-producing T cells NK suppressed RSV...
Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T-cell numbers CD28
Progressive tissue fibrosis, including idiopathic pulmonary fibrosis (IPF), is characterized by excessive recruitment of fibroblasts to sites injury and unremitting extracellular matrix deposition associated with severe morbidity mortality. However, the molecular mechanisms that control progressive IPF have yet be fully determined. Previous studies suggested invasive drive disease progression in IPF. Here, we report profiling noninvasive from patients healthy donors. Pathway analysis...
Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles tissue damage through immunity fibrotic remodeling, respectively. In the present study, we addressed following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation activation? To this end, analyzed bone marrow-derived macrophages from mice with...
Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease of unknown etiology and limited therapeutic options. In this report, we characterize what believe novel CCR10+ epithelial cell population in IPF lungs. There was significant increase the percentage cells relative to normal explants their numbers significantly correlated remodeling humanized NSG mice. Cultured CCR10-enriched promoted fibroblast invasion collagen 1 secretion. Single-cell RNA sequencing analysis showed...
Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted cell apoptosis whereas intracellular maintained epithelium viability during repair. Unlike normal COPD lungs, IPF lungs were significantly increased inverse was evident for Clusterin. In vitro in vivo studies demonstrated while intercellular modulated expression DNA repair proteins, MSH2, MSH6, OGG1 BRCA1. The...
Rationale: Aberrant lung remodeling in idiopathic pulmonary fibrosis (IPF) is characterized by elevated MMP9 (matrix metalloproteinase 9) expression, but the precise role of this matrix disease has yet to be fully elucidated.Objectives: To evaluate antifibrotic effects inhibition on IPF.Methods: Quantitative genomic, proteomic, and functional analyses both vitro vivo were used determine expression IPF cells profibrotic mechanisms.Measurements Main Results: In present study, we demonstrate...
Abstract Interleukin (IL)-33 is an important cytokine in the tumour microenvironment; it known to promote growth and metastasis of solid cancers, such as gastric, colorectal, ovarian breast cancer. Our group demonstrated that IL-33/ST2 pathway enhances development squamous cell carcinoma (SCC). Conversely, other researchers have reported IL-33 inhibits progression. In addition, crosstalk between IL-33, cancer cells immune SCC remains unknown. The aim this study was investigate effect on...
Toll-like receptor (TLR) activation has been implicated in acetaminophen (APAP)-induced hepatotoxicity. Herein, we hypothesize that TLR3 significantly contributed to APAP-induced liver injury. In fasted wildtype (WT) mice, APAP caused significant cellular necrosis, edema, and inflammation the liver, de novo expression of was found be necessary for failure. Specifically, tissues from similarly TLR3-deficient (tlr3(-/-) ) mice exhibited less histological biochemical evidence injury after...
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant repair that diminishes lung function via mechanisms remain poorly understood. CC chemokine receptor (CCR10) and its ligand CCL28 were both elevated in IPF compared with normal donors. CCR10 was highly expressed various cells from lungs, most notably stage-specific embryonic antigen-4-positive mesenchymal progenitor (MPCs). In vitro, promoted the proliferation of CCR10+ MPCs while CRISPR/Cas9-mediated targeting resulted death...