A5103627020- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pain Management and Treatment
- Neonatal Respiratory Health Research
- Cardiac Imaging and Diagnostics
- Musculoskeletal pain and rehabilitation
- Pain Mechanisms and Treatments
- Medical Imaging and Pathology Studies
- Acute Myocardial Infarction Research
- Cardiac Health and Mental Health
- Cardiovascular Function and Risk Factors
- Pleural and Pulmonary Diseases
- Pulmonary Hypertension Research and Treatments
- Cardiac Arrest and Resuscitation
- Inhalation and Respiratory Drug Delivery
- Coronary Interventions and Diagnostics
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory Support and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Pediatric health and respiratory diseases
- Radiation Dose and Imaging
- Telomeres, Telomerase, and Senescence
- Antiplatelet Therapy and Cardiovascular Diseases
- Cardiac, Anesthesia and Surgical Outcomes
- Occupational and environmental lung diseases
Vanderbilt University Medical Center
2007-2025
VA Tennessee Valley Healthcare System
2005-2024
Stony Brook University Hospital
1996-2024
Stony Brook University
2014-2023
Vanderbilt University
2009-2019
State University of New York
2002-2016
Pulmonary and Allergy Associates
2009-2016
United States Department of Veterans Affairs
2015
Stony Brook Medicine
2005-2015
Immunovaccine (Canada)
2011
Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering the disease are unknown. Germ-line mutations in genes hTERT hTR, encoding telomerase reverse transcriptase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia fibrosis.To test hypothesis that idiopathic may be caused by short telomeres, we screened 73 probands Vanderbilt Familial Pulmonary Fibrosis Registry...
Recent evidence suggests that dysfunctional type II alveolar epithelial cells (AECs) contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Based on hypothesis disease-causing mutations in surfactant protein C (SFTPC) provide an important paradigm for studying IPF, we investigated a potential mechanism AEC dysfunction suggested result from mutant SFTPC expression: induction endoplasmic reticulum (ER) stress and unfolded response (UPR). We evaluated biopsies 23 IPF patients...
Rationale: Lung fibroblasts are key mediators of fibrosis resulting in accumulation excessive interstitial collagen and extracellular matrix, but their origins not well defined.Objectives: We aimed to elucidate the contribution lung epithelium–derived via epithelial–mesenchymal transition (EMT) intratracheal bleomycin model.Methods: Primary type II alveolar epithelial cells were cultured from Immortomice exposed transforming growth factor-β1 epidermal factor. Cell fate reporter mice that...
Evidence of endoplasmic reticulum (ER) stress has been found in lungs patients with familial and sporadic idiopathic pulmonary fibrosis. We tested whether ER causes or exacerbates lung fibrosis by ( i ) conditional expression a mutant form surfactant protein C (L188Q SFTPC interstitial pneumonia ii intratracheal treatment the misfolding agent tunicamycin. developed transgenic mice expressing L188Q exclusively type II alveolar epithelium using Tet-On system. Expression induced stress, as...
Single-dose intratracheal bleomycin has been instrumental for understanding fibrotic lung remodeling, but fails to recapitulate several features of idiopathic pulmonary fibrosis (IPF). Since IPF is thought result from recurrent alveolar injury, we aimed develop a repetitive model that results in with key characteristics human disease, including epithelial cell (AEC) hyperplasia. Wild-type and fate reporter mice expressing β-galactosidase cells lineage were given after intubation, lungs...
Section:ChooseTop of pageAbstract <<Biology Alveolar Injur...Role ECMPreclinical ModelingThe Role Inflammation ...Genetic, Epigenetic, and ...Translation Discoverie...SummaryReferencesCITING ARTICLES
Rationale: Up to 20% of cases idiopathic interstitial pneumonia cluster in families, comprising the syndrome familial (FIP); however, genetic basis FIP remains uncertain most families.Objectives: To determine if new disease-causing rare variants could be identified using whole-exome sequencing affected members from providing additional insights into disease pathogenesis.Methods: Affected subjects 25 kindreds were selected an ongoing registry for genomic DNA. Candidate confirmed by Sanger...
While idiopathic pulmonary fibrosis (IPF) is one of the most common forms interstitial lung disease, aetiology IPF poorly understood. Familial cases suggest a genetic basis for some disease. Recent reports have linked mutations in surfactant protein C (SFTPC) with familial fibrosis, including large family which number members were diagnosed usual pneumonitis (UIP), pathological correlate to IPF. Because this finding we searched SFTPC cohort sporadic UIP and non-specific (NSIP).The gene was...
Expression of mutant surfactant protein C (SFTPC) results in endoplasmic reticulum (ER) stress type II alveolar epithelial cells (AECs). AECs have been implicated as a source lung fibroblasts via epithelial-to-mesenchymal transition (EMT); therefore, we investigated whether ER contributes to EMT possible mechanism for fibrotic remodeling. was induced by tunicamyin administration or stable expression (L188Q) SFTPC AEC lines. Both tunicamycin treatment and the unfolded response. With...
Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form idiopathic pneumonia, carry increased risk for developing lung disease.Studying these at-risk individuals provides a unique opportunity to investigate early stages FIP pathogenesis and develop predictive models disease onset.Seventy-five asymptomatic first-degree (mean age, 50.8 yr) underwent blood sampling high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72...
Background Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical biopsy is frequently required. Recently new technique for bronchoscopic has been developed using flexible cryo-probes. In this study we describe our experience cryobiopsy disease. Methods A retrospective subjects who had undergone evaluation DPLD at an academic tertiary care center from January 1, 2012 through 15, 2013 was...
Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent are largely unknown.
The incidence of idiopathic pulmonary fibrosis (IPF) increases with age. mechanisms that underlie the age-dependent risk for IPF are unknown. Based on studies suggest an association and γherpesvirus infection, we infected young (2-3 mo) old (≥18 C57BL/6 mice murine 68. Acute 68 infection in aging resulted severe pneumonitis compared animals. Progressive clinical deterioration lung late chronic phase was observed exclusively diminution tidal volume. Infected showed higher expression...
Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes HPS, we investigated whether crosstalk between AECs macrophages determines susceptibility. We found that from HPS mice produce excessive MCP-1, which was lungs...
Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface the external environment; however, role system chronic lung diseases incompletely understood.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which repetitive epithelial injury and incomplete alveolar repair result accumulation of profibrotic intermediate/transitional “aberrant” cell states. The mechanisms leading to the emergence persistence aberrant populations distal remain incompletely understood. By interrogating single-cell RNA sequencing (scRNA-seq) data from patients with IPF mouse model repeated injury, we identified persistent activation...
Because fibroblasts produce collagen and other extracellular matrix components that are deposited during tissue fibrosis, defining the behavior of these cells is critical to understanding pathogenesis fibrotic diseases. We investigated utility fibroblast-specific protein 1 (FSP1), a member calmodulin S100 troponin C superfamily, for identifying lung in murine model pulmonary fibrosis induced by intratracheal administration bleomycin. Protein mRNA expression FSP1 was minimal untreated lungs,...