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Am J Respir Cell Mol Biol 2022 May 25. Epub 2022 May 25.

Université Paris Cité, Inserm, PHERE, Paris, France;

Am J Respir Cell Mol Biol 2022 May 25. Epub 2022 May 25.

Université de Sherbrooke, 7321, Department of Immunology and Cell Biology, Sherbrooke, Quebec, Canada;

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with no curative pharmacological treatment. Current preclinical models fail to accurately reproduce human pathophysiology and are therefore poor predictors of clinical outcomes. Here, we investigated whether the chick embryo chorioallantoic membrane (CAM) assay supports the implantation of xenografts derived from IPF lung tissue and primary IPF lung fibroblasts and can be used to evaluate the efficacy of antifibrotic drugs. Read More

Am J Respir Cell Mol Biol 2022 May 24. Epub 2022 May 24.

University of Colorado, School of Medicine, Department of Medicine, Aurora, Colorado, United States.

We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis model. Read More

Am J Respir Cell Mol Biol 2022 May 18. Epub 2022 May 18.

Virginia Commonwealth University Department of Pediatrics, 466504, Richmond, Virginia, United States;

Am J Respir Cell Mol Biol 2022 May 18. Epub 2022 May 18.

Brown University, Molecular Microbiology and Immunology, Providence, Rhode Island, United States;

Idiopathic pulmonary fibrosis (IPF) is a particularly deadly form of pulmonary fibrosis with unknown reason. In patients with IPF, high serum and lung levels of CHI3L1 can be detected and are associated with poor survival. However, the roles of CHI3L1 in these diseases have not been fully elucidated. Read More

Am J Respir Cell Mol Biol 2022 May 17. Epub 2022 May 17.

University of Alabama at Birmingham, 9968, Birmingham, Alabama, United States;

Am J Respir Cell Mol Biol 2022 May 17. Epub 2022 May 17.

University of Wisconsin-Madison, 5228, Pediatrics, Madison, Wisconsin, United States.

Chromosome 17q12-q21 is the most replicated genetic locus for childhood-onset asthma. Polymorphisms in this locus containing approximately 10 genes interact with a variety of environmental exposures in the home and outdoors to modify asthma risk. However, the functional basis for these associations and their linkages to the environment have remained enigmatic. Read More

Am J Respir Cell Mol Biol 2022 May 17. Epub 2022 May 17.

Amsterdam UMC - Locatie VUMC, 1209, Pulmonary Diseases, Amsterdam, Netherlands.

Am J Respir Cell Mol Biol 2022 May 17. Epub 2022 May 17.

University of Pittsburgh, 6614, Division of PACCM, Department of Medicine, Pittsburgh, Pennsylvania, United States;

Am J Respir Cell Mol Biol 2022 May 13. Epub 2022 May 13.

Amsterdam UMC Locatie AMC, 26066, Pediatric Intensive Care Unit, Emma Children's Hospital, Amsterdam, Netherlands;

Am J Respir Cell Mol Biol 2022 May 13. Epub 2022 May 13.

University of Washington, 7284, Medicine, Seattle, Washington, United States.

Am J Respir Cell Mol Biol 2022 May 13. Epub 2022 May 13.

INSERM, 27102, UMR_S 999, Le Plessis-Robinson, France.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by the dysfunction of pulmonary endothelial cells (ECs) and obstructive vascular remodeling. The non-receptor tyrosine kinase c-Abelson (cAbl) plays central roles in regulating cell-cycle arrest, apoptosis, and senescence after cellular stress. We hypothesized that cAbl is down-activated in experimental and human PAH, thus leading to reduced DNA integrity and angiogenic capacity of pulmonary ECs from PAH patients (PAH-ECs). Read More

Am J Respir Cell Mol Biol 2022 May 12. Epub 2022 May 12.

AP-HP, Hôpital Bichat, Service de Pneumologie A, DHU FIRE, Université Paris Diderot, Paris, France;

IPF is a devastating lung disease with limited therapeutic possibilities. FGF19, an endocrine FGF, was recently shown to decrease liver fibrosis. To ask whether FGF19 had anti-fibrotic properties in the lung and decipher its effects on common features associated with lung fibrogenesis. Read More

Am J Respir Cell Mol Biol 2022 May 12. Epub 2022 May 12.

State Key Laboratory of Pharmaceutical Biotechnology, 384750, Medical School, Nanjing University, Nanjing, China.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children. Axl, a TAM family receptor tyrosine kinase (RTK), has been demonstrated as a receptor mediating enveloped virus infection. Here we show that Axl functions as a suppressor of antiviral response during RSV infection. Read More

Am J Respir Cell Mol Biol 2022 May 6. Epub 2022 May 6.

Imperial College London, 4615, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland;

Am J Respir Cell Mol Biol 2022 May 6. Epub 2022 May 6.

Ohio State University Wexner Medical Center, 12306, Internal Medicine, PCCS, Columbus, Ohio, United States.

Am J Respir Cell Mol Biol 2022 May 6. Epub 2022 May 6.

Liege University, 26658, GIGA Institute, Liege, Belgium;

Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity and whose diversity in health and disease is a subject of intense investigations. Yet, it remains unclear to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Here, we aimed to explore heterogeneity of human AM isolated from healthy non-smokers, non-COPD smokers and COPD smokers by analyzing bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell RNA-sequencing. Read More

Am J Respir Cell Mol Biol 2022 May 4. Epub 2022 May 4.

Nanjing Medical University, 12461, Nanjing, China;

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have been evaluated in many studies as promising therapeutic agents for pulmonary hypertension (PH). However, low yields and heterogeneity are a major barrier in the translational utility of EVs for clinical studies. To address these limitations, we fabricated MSCs derived nanovesicles (MSC-NVs) by serial extrusion through filters resulting in MSC-NVs with characteristics similar to conventional EVs but with much higher production yields. Read More

Am J Respir Cell Mol Biol 2022 May 4. Epub 2022 May 4.

Royal College of Surgeons in Ireland, Respiratory Research Division - Dept of Medicine, Dublin, Ireland;

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by neutrophil-dominated inflammation resulting in emphysema. The cholesterol-rich neutrophil outer plasma membrane plays a central role in adhesion and subsequent transmigration to underlying tissues. This study aimed to investigate mechanisms of increased neutrophil adhesion in AATD, and whether AAT augmentation therapy abrogates this effect. Read More

Am J Respir Cell Mol Biol 2022 May 3. Epub 2022 May 3.

Michigan State University, 3078, Pharmacology and Toxicology, East Lansing, Michigan, United States.

Am J Respir Cell Mol Biol 2022 Apr 29. Epub 2022 Apr 29.

University of North Carolina, Pathology and Laboratory Medicine , Chapel Hill, North Carolina, United States;

The dynamics describing the vicious cycle characteristic of CF lung disease, initiated by stagnant mucus and perpetuated by infection and inflammation, remain unclear. Here we determine the effect of the CF airway milieu, with persistent muco-obstruction, resident pathogens, and inflammation, on the mucin quantity/quality that govern lung disease pathogenesis/progression. The concentrations of MUC5AC and MUC5B, were measured and characterized in sputum samples from CF (N=44) and healthy (N=29) subjects with respect to their macromolecular properties, degree of proteolysis, and glycomics diversity. Read More

Am J Respir Cell Mol Biol 2022 May;66(5):ii

Am J Respir Cell Mol Biol 2022 May;66(5):580-581

University of Colorado Denver Aurora, Colorado.

Am J Respir Cell Mol Biol 2022 May;66(5):577-579

University of Washington Seattle, Washington.

Am J Respir Cell Mol Biol 2022 Apr 26. Epub 2022 Apr 26.

Sydney Children's Hospital, Department of Respiratory Medicine, Sydney, New South Wales, Australia.

A significant challenge to making targeted CFTR modulator therapies accessible to all individuals with cystic fibrosis (CF) are many mutations in the CFTR gene that can cause CF, most of which remain uncharacterized. Here, we characterized the structural and functional defects of the rare CFTR mutation R352Q - with potential role contributing to intrapore chloride ion permeation - in patient-derived cell models of the airway and gut. CFTR function in differentiated nasal epithelial cultures and matched intestinal organoids was assessed using ion transport assay and forskolin-induced swelling (FIS) assay respectively. Read More

Am J Respir Cell Mol Biol 2022 Apr 25. Epub 2022 Apr 25.

Vanderbilt University Medical Center, 12328, Medicine, Nashville, Tennessee, United States.

Immune cells have been implicated in Idiopathic Pulmonary Fibrosis (IPF), but the phenotypes and effector mechanisms of these cells remain incompletely characterized. We performed mass cytometry to quantify immune/inflammatory cell subsets in lungs of 12 patients with IPF and 15 organ donors without chronic lung disease and utilized existing single-cell RNA-sequencing (scRNA-seq) data to investigate transcriptional profiles of immune cells over-represented in IPF. Among myeloid cells, we found increased numbers of alveolar macrophages (AMØs) and dendritic cells (DCs) in IPF, as well as a subset of monocyte-derived DC. Read More

Am J Respir Cell Mol Biol 2022 Apr 21. Epub 2022 Apr 21.

Nationwide Children's Hospital, 2650, Perinatal, Columbus, Ohio, United States.

Am J Respir Cell Mol Biol 2022 Apr 20. Epub 2022 Apr 20.

Children's Hospital of Pittsburgh of UPMC, Pediatrics, Pittsburgh, Pennsylvania, United States;

Am J Respir Cell Mol Biol 2022 Apr 20. Epub 2022 Apr 20.

OHIO STATE UNIVERSITY, COLLEGE OF VETERINARY MEDICINE, Columbus, Ohio, United States;

Development of ARDS in influenza A virus (IAV)-infected mice is associated with inhibition of alveolar type II (ATII) epithelial cell de novo phosphatidylcholine synthesis and administration of the phosphatidylcholine precursor CDP-choline attenuates IAV-induced ARDS in mice. We hypothesized inhibition of phosphatidylcholine synthesis would also impact the function of ATII cell mitochondria. To test this hypothesis, adult C57BL/6 mice of both sexes were inoculated intranasally with 10,000 p. Read More

Am J Respir Cell Mol Biol 2022 Apr 6. Epub 2022 Apr 6.

Hospital of the Goethe University Frankfurt, 14984, KAIS, Frankfurt am Main, Germany;