A5044521727- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Sarcoidosis and Beryllium Toxicity Research
- Asthma and respiratory diseases
- Cancer, Hypoxia, and Metabolism
- Respiratory Support and Mechanisms
- Pulmonary Hypertension Research and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Fibroblast Growth Factor Research
- Immune Response and Inflammation
- Respiratory viral infections research
- Influenza Virus Research Studies
- Autophagy in Disease and Therapy
- Circular RNAs in diseases
- Systemic Sclerosis and Related Diseases
- MicroRNA in disease regulation
- Congenital Diaphragmatic Hernia Studies
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
- Bacteriophages and microbial interactions
- Sinusitis and nasal conditions
- Inhalation and Respiratory Drug Delivery
- IL-33, ST2, and ILC Pathways
- Macrophage Migration Inhibitory Factor
- Histiocytic Disorders and Treatments
Yale University
2008-2025
University of New Haven
2024
SleepMed
2016-2022
Pulmonary and Critical Care Associates
2017-2022
University of Alabama at Birmingham
2008
Chitinase 3–like 1 protects against lung injury but has a profibrotic role during the repair phase.
Abstract Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked centennial of Felix d’Hérelle’s first publication on clinical applications phages. At Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established offer safe potent phages single-patient investigational new drug while recognizing time constraints imposed by infection(s). This study provides...
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...
Bone marrow‐derived cells (BMDCs) can adopt an epithelial phenotype in the lung following bone marrow transplantation (BMT). This phenomenon has been assumed to result from injury that occurs with myeloablative radiation. To date, no study related degree of chimerism damage induced by preconditioning for BMT. Such a goal is crucial understanding local host factors promote engraftment BMDCs as epithelia. We undertook this aim performing sex‐mismatched using variety regimens and comparing...
Abstract IL-13 is a critical cytokine at sites of Th2 inflammation. In these locations it mediates its effects via receptor complex, which contains IL-4Rα and IL-13Rα1. A third, high-affinity receptor, IL-13Rα2, also exists. Although was initially felt to be decoy this has not been formally demonstrated the role(s) recently become controversial. To define IL-13Rα2 in IL-13-induced pulmonary inflammation remodeling, we compared lung-targeted transgenic mice with wild-type null loci. We...
Pulmonary fibrosis is a progressive and often fatal condition that believed to be partially orchestrated by macrophages. Mechanisms control migration of these cells into within the lung remain undefined. We evaluated contributions semaphorin receptor, plexin C1 (PLXNC1), exocytic calcium sensor, synaptotagmin 7 (Syt7), in processes. role PLXNC1 macrophage using Boyden chambers scratch tests, characterized its contribution experimentally induced mice, defined mechanism for our observations....
Background Sarcoidosis is a multisystem granulomatous disease of unknown origin with variable and often unpredictable course pattern organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative distinct phenotypic traits. Methods RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well-characterised patients pulmonary sarcoidosis enrolled in the multicentre Genomic Research Alpha-1...
Host response aimed at eliminating the infecting pathogen, as well pathogen itself, can cause tissue injury. Tissue injury leads to release of a myriad cellular components including mitochondrial DNA, which host senses through pattern recognition receptors. How sensing by shapes anti-pathogen remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), binds unmethylated CpG DNA sequences such those present bacterial and DNA. To avoid direct...
Cigarette smoke (CS) creates a "cancer field" in the lung that promotes malignant transformation. The molecular changes within this field are not fully characterized. We examined significance of microRNA-1 (miR-1) downregulation as one these changes. found tumor miR-1 levels three non-small cell cancer cohorts show inverse correlations with smoking burden. Lung MiR-1 follow spatial gradient, have prognostic significance, and correlate inversely markers injury. In CS-exposed lungs, is...
Staphylococcus aureus (SA), the most common cystic fibrosis (CF) lung pathogen, is uniquely capable of producing superantigen (SAg) exotoxins, which are potent activators immune system. Although proinflammatory roles SA-SAgs well-established, their role in immunopathogenesis CF disease unexplored. Herein, we demonstrate that 60-80% pediatric and adult SA isolates carried at least one SA-SAg gene, with former harboring (Staphylococcal enterotoxin A B) more frequently (30-60%). Biofilms...
Cell fusion is one mechanism by which bone marrow-derived cells (BMDCs) take on the gene expression pattern of nonhematopoietic cells. This process occurs in a number organs with postengraftment injury but has never been found lung. We performed marrow (BM) transplant murine model lung inflammation to test whether transplanted BMDCs develop lung-specific fusing diseased pneumocytes. Mice lacking protein surfactant C (Sp-C) were lethally irradiated, sex mismatched wild-type marrow, and...
Vascular endothelial growth factor down-regulates microRNA-1 (miR-1) in the lung endothelium, and cells play a critical role tumor progression angiogenesis. To examine clinical significance of miR-1 non-small cell cancer (NSCLC) its specific endothelium. levels were measured by Taqman assay. Endothelial isolated magnetic sorting. We used vascular cadherin promoter to create vascular-specific lentiviral vector an inducible transgenic mouse. KRASG12D mut/Trp53-/- (KP) mice, lung-specific Lewis...
The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association fibrotic stimuli and perturbed innate immunity. cytosolic DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated inflammation fibrosis, but its involvement SSc-ILD remains unknown. We examined cGAS expression, activity, therapeutic potential using human biospecimens, cultured fibroblasts, precision cut lung slices (PCLS), a...
The mechanisms by which excessive systemic activation of adaptive T lymphocytes, as in cytokine release syndrome (CRS), leads to innate immune cell-mediated acute lung injury (ALI) or respiratory distress syndrome, often the absence any infection, remains unknown. Here, we investigated roles IFN-γ and IL-17A, key T-cell cytokines significantly elevated patients with CRS, immunopathogenesis CRS-induced extrapulmonary ALI. CRS was induced wild-type (WT), IL-17A- knockout (KO) human leukocyte...
Sarcoidosis is an unpredictable granulomatous disease in which African Americans disproportionately experience aggressive phenotypes. Mitochondrial DNA (mtDNA) released by cells response to various stressors contributes tissue remodelling and inflammation. While extracellular mtDNA has emerged as a biomarker multiple diseases, its relevance sarcoidosis remains unknown. We aimed define association between clinical features of sarcoidosis. Extracellular concentrations were measured using...
Idiopathic pulmonary fibrosis is increasingly associated with nerve-driven processes and endogenous innate immune ligands such as mitochondrial DNA (mtDNA). Interestingly, a connection between these entities has not been explored. Here, we report that noradrenaline (NA) derived from the lung's adrenergic nerve supply drives α-smooth muscle actin (αSMA)-expressing fibroblast accumulation via mechanisms involving α1 adrenoreceptors mtDNA. Using bleomycin model, compared ablation of surgical...
Abstract Host response aimed at eliminating the infecting pathogen, as well pathogen itself, can cause tissue injury. Tissue injury leads to release of a myriad cellular components including mitochondrial DNA, which host senses through pattern recognition receptors. How sensing by shapes anti-pathogen remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), binds unmethylated CpG DNA sequences such those present bacterial and DNA. To avoid...
Introduction The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation abnormal extracellular matrix, which is partly result an imbalance in collagen synthesis, cross-linking and degradation. During this process, fragments or neoepitopes, are released into circulation. significance these circulating neoepitopes remains unknown. Methods We employed plasma samples from patients with enrolled A Case Control Etiologic Study Sarcoidosis (ACCESS) Genomic Research...
Asthma health disparities are widely recognized, with worse outcomes in children from low income families. In a Medical-Legal Partnership (MLP), an attorney is embedded healthcare setting to address social determinants of health. We studied whether MLP could impact asthma exacerbation rates vulnerable urban population at academic children's hospital.The study comprised who were referred the between 2013 and 2017. compared utilization for exacerbations managed primary care, emergency...
Aims. Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at levels (>95%). Results. Effects hyperoxia (100% oxygen) were studied mice genetically inhibited EGFR and wild-type littermates. Despite established repair, inhibition led improved survival reduced acute injury, which prompted an investigation into this...
Background Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that causes early onset pulmonary emphysema and airways obstruction. The complete mechanisms via which AATD lung disease are not fully understood. To improve our understanding of the pathogenesis AATD, we investigated gene expression profiles bronchoalveolar lavage (BAL) peripheral blood mononuclear cells (PBMCs) in individuals. Methods We performed RNA-Seq on RNA extracted from matched BAL PBMC samples isolated 89...