A5050796822- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric health and respiratory diseases
- Antimicrobial Peptides and Activities
- Cancer Cells and Metastasis
- Respiratory Support and Mechanisms
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- RNA modifications and cancer
- Cystic Fibrosis Research Advances
- Tracheal and airway disorders
- Cell Image Analysis Techniques
- AI in cancer detection
- Cancer-related molecular mechanisms research
- Congenital Diaphragmatic Hernia Studies
- Pluripotent Stem Cells Research
- Medical Imaging Techniques and Applications
- Neuropeptides and Animal Physiology
- Respiratory viral infections research
- Immune cells in cancer
- Protein Hydrolysis and Bioactive Peptides
- Nutritional Studies and Diet
- Lung Cancer Treatments and Mutations
- Asthma and respiratory diseases
- Biological Research and Disease Studies
Cornell University
2012-2022
Weill Cornell Medicine
2022
University of Southern Denmark
2018
New York Proton Center
2013
Memorial Sloan Kettering Cancer Center
2012
Universities of Giessen and Marburg Lung Center
2010
Universitätsklinikum Gießen und Marburg
2007-2010
Philipps University of Marburg
2005-2008
Abstract When exposed to a specific microenvironment, macrophages acquire either M1- or M2-polarized phenotypes associated with inflammation and tissue remodeling, respectively. Alveolar (AM) directly interact environmental stimuli such as cigarette smoke, the major risk factor for chronic obstructive pulmonary disease (COPD), characterized by lung remodeling. Transcriptional profiling of AM obtained bronchoalveolar lavage 24 healthy nonsmokers, 34 smokers, 12 COPD smokers was performed test...
Chronic obstructive pulmonary disease is a heterogeneous disorder with varying presentation and progression, but limited disease-modifying therapies.It increasingly evident that lung function trajectories in COPD differ significantly differences are detectable young adulthood.It important to distinguish "early disease" meaning the first signs of developing individual from "late mild may be severity an older have been present for decades.We propose operational definition early as occurring...
Rationale: Remodeling and loss of distal conducting airways, including preterminal terminal bronchioles (pre-TBs/TBs), underlie progressive airflow limitation in chronic obstructive pulmonary disease (COPD). The cellular basis these structural changes remains unknown. Objectives: To identify biological pre-TBs/TBs COPD at single-cell resolution determine their origin. Methods: We established a novel method airway dissection performed transcriptomic profiling 111,412 cells isolated from...
Antimicrobial peptides are endogenous antibiotics that directly inactivate microorganisms and in addition have a variety of receptor-mediated functions. LL-37/hCAP-18 is the only cathelicidin found humans involved angiogenesis regulation innate immune system. The aim present study was to characterize role peptide LL-37 wound closure airway epithelium cell line NCI-H292 primary epithelial cells. stimulated healing mechanically induced wounds monolayers differentiated epithelium. This effect...
Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover in response to injury, the cells function as stem/progenitor for other types. objective this study is better understand epithelial biology by defining gene expression signature population. Methodology/Principal Findings Bronchial brushing was used obtain from healthy nonsmokers. Microarrays were assess transcriptome purified comparison differentiated...
Human airway epithelial cells cultured in vitro at the air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, produces mucin. These are widely used models of differentiation, injury, repair. To assess how closely transcriptome ALI matches vivo cells, we microarrays to compare human large with obtained via bronchoscopy brushing. Gene expression profiling showed global gene correlated well between brushed but some differences. patterns mirrored...
The small airway epithelium (SAE), the cell population that covers human surface from 6th generation of branching to alveoli, is major site lung disease caused by smoking. focus this study provide quantitative assessment SAE transcriptome in resting state and response chronic cigarette smoking using massive parallel mRNA sequencing (RNA-Seq). data demonstrate 48% expressed genes are ubiquitous, shared with many tissues, 52% enriched population. most highly gene, SCGB1A1, characteristic Clara...
The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of the innate host defense system at surfaces body. Besides its direct activity, interacts with different cell types. Dendritic cells (DCs) play a central role in mucosal defense. It was aim study to determine whether LL-37 modulates response DCs pathogen-associated molecular patterns. Monocyte-derived were stimulated Toll-like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured classical...
The airway epithelium of smokers acquires pathological phenotypes, including basal cell (BC) and/or goblet hyperplasia, squamous metaplasia, structural and functional abnormalities ciliated cells, decreased number secretoglobin (SCGB1A1)-expressing secretory a disordered junctional barrier. In this study, we hypothesized that smoking alters epithelial structure through modification BC function via an EGF receptor (EGFR)-mediated mechanism. Analysis the revealed EGFR is enriched in BCs,...
Small airways are the primary site of pathologic changes in chronic obstructive pulmonary disease (COPD), major smoking-induced lung disorder.On basis concept proximal-distal patterning that determines regional specialization airway epithelium during development, we hypothesized a similar program operates adult human being altered by smoking, leading to decreased identity small (SAE).The proximal and distal signatures were identified comparing transcriptomes large samples obtained...
Genome-wide association studies (GWAS) and candidate gene have identified a number of risk loci associated with the smoking-related disease COPD, disorder that originates in airway epithelium. Since basal cell (BC) stem/progenitor cells exhibit earliest abnormalities smoking (hyperplasia, squamous metaplasia), we hypothesized smoker BC dysregulated transcriptome, enriched, part, at known GWAS/candidate loci. Massive parallel RNA sequencing was used to compare transcriptome purified from...
The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease lung cancer. In this study, we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) is induced by smoking in human as a result (EGF)-driven BC stem/progenitor cells. turn, AREG unique EGFR...
Epithelial cells (ECs) continuously interact with microorganisms and detect their presence via different pattern-recognition receptors (PRRs) including Toll-like (TLRs). Ligation of epithelial TLRs by pathogens is usually associated the induction pro-inflammatory mediators antimicrobial factors. In this study, using human airway ECs as a model, we found that detection microbial patterns directly regulates tissue homeostasis. Staphylococcus aureus (S. aureus) signaling TLR2 TLR5 induce set...
In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination epithelial samples obtained bronchoscopy and brushing was excluded immunohistochemistry staining, observation upregulation POU2AF1 purified basal stem/progenitor cells...
Abstract The cathepsin inhibitor Cystatin A (CSTA) has antiapoptotic properties linked with neoplastic changes in squamous cell epithelium, where it been proposed as a diagnostic and prognostic marker of lung cancer. Notably, cystatin is upregulated dysplastic prompting us to hypothesize that might be modulated chronic obstructive pulmonary disease (COPD), small airway epithelial (SAE) disorder risk factor for non–small cancer (NSCLC) subset smokers. Here we report genetic variation,...
CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) lung cancer are both smoking-related disorders associated with airway disorder inflammation, we hypothesized epithelium responds to cigarette smoking altered CXCL14 gene expression, contributing disease-relevant phenotype. Using genome-wide microarrays subsequent immunohistochemical analysis, data demonstrate...