Michael F. Beers
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View article: Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms
Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms Open
Surfactant Protein C (SP-C), a hydrophobic protein exclusively synthesized and secreted by alveolar type II (AT2) cells, is important for reducing alveolar surface tension in the distal lung. Chronic interstitial pulmonary diseases have be…
View article: REGULATORY T CELLS PROTECT AGAINST ABERRANT REMODELING IN A MOUSE MODEL OF PULMONARY FIBROSIS
REGULATORY T CELLS PROTECT AGAINST ABERRANT REMODELING IN A MOUSE MODEL OF PULMONARY FIBROSIS Open
Regulatory T (Treg) cells are well recognized for their role in immune regulation; however, their role in tissue regeneration is not fully understood. This study demonstrates such a role of Tregs in a published preclinical murine model of …
View article: Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis
Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis Open
Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously demonstrated that expression of an AT2 cell-exclusive disease-associated prote…
View article: Stem cells, cell therapies, and bioengineering in lung biology and diseases 2023
Stem cells, cell therapies, and bioengineering in lung biology and diseases 2023 Open
Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade, increasing evidence from preclinical mode…
View article: Impaired AMPK Control of Alveolar Epithelial Cell Metabolism Promotes Pulmonary Fibrosis
Impaired AMPK Control of Alveolar Epithelial Cell Metabolism Promotes Pulmonary Fibrosis Open
Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously described that expression of an AT2 cell exclusive disease-associated protein …
View article: Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report
Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report Open
Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung …
View article: PGF2α signaling drives fibrotic remodeling and fibroblast population dynamics in mice
PGF2α signaling drives fibrotic remodeling and fibroblast population dynamics in mice Open
Idiopathic pulmonary fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effect…
View article: Disruption of Prostaglandin F<sub>2α</sub>Receptor Signaling Attenuates Fibrotic Remodeling and Alters Fibroblast Population Dynamics in A Preclinical Murine Model of Idiopathic Pulmonary Fibrosis
Disruption of Prostaglandin F<sub>2α</sub>Receptor Signaling Attenuates Fibrotic Remodeling and Alters Fibroblast Population Dynamics in A Preclinical Murine Model of Idiopathic Pulmonary Fibrosis Open
Idiopathic Pulmonary Fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effect…
View article: Regulatory T cells in the fibrotic milieu: ontological characterization from initiation through remodeling in a murine model of spontaneous pulmonary fibrosis
Regulatory T cells in the fibrotic milieu: ontological characterization from initiation through remodeling in a murine model of spontaneous pulmonary fibrosis Open
Using exogenous injury models, regulatory T cells (Tregs) have been shown to have both tissue protective (immunosuppressive) as well as deleterious (pro-fibrotic) effects on the lung. The goal of this study was to define the ontogeny of Tr…
View article: Chronic Expression of a Clinical <i>SFTPC</i> Mutation Causes Murine Lung Fibrosis with Idiopathic Pulmonary Fibrosis Features
Chronic Expression of a Clinical <i>SFTPC</i> Mutation Causes Murine Lung Fibrosis with Idiopathic Pulmonary Fibrosis Features Open
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease. A barrier to developing more effective therapies for IPF is the dearth of preclinical models that recapitulate the early pathobiology of this …
View article: Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells
Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells Open
Dysfunction of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, is implicated in pulmonary disease pathogenesis, highlighting the importance of human in vitro models. However, AEC2-like cells in cultur…
View article: Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells
Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells Open
Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutati…
View article: SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells
SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells Open
SARS-CoV-2 is the third lethal respiratory coronavirus, after MERS-CoV and SARS-CoV, to emerge this century, causing millions of deaths worldwide. Other common coronaviruses such as HCoV-OC43 cause less severe respiratory disease.
View article: Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features
Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features Open
Background/Objective Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goa…
View article: Microstructured Hydrogels to Guide Self‐Assembly and Function of Lung Alveolospheres
Microstructured Hydrogels to Guide Self‐Assembly and Function of Lung Alveolospheres Open
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro and for therapeutic cell transplantation. Despite their potential, current protocols to grow these organoids almost exclus…
View article: Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils
Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils Open
Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulatio…
View article: Methodological caveats regarding “Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant”
Methodological caveats regarding “Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant” Open
The manuscript by Dickens and co-workers examines biosynthesis of surfactant protein C (SP-C). However, limitations in the model system used and bioproperties of SP-C necessitate further studies to support many of the stated conclusions…
View article: SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells
SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells Open
SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available, or its citizens are hesitant to become v…
View article: Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis
Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis Open
View article: Microstructured hydrogels to guide self-assembly and function of lung alveolospheres
Microstructured hydrogels to guide self-assembly and function of lung alveolospheres Open
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro and for therapeutic cell transplantation. Despite their potential, current protocols to grow these organoids almost exclus…
View article: Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease
Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease Open
View article: Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2
Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion of Nedd4-2 Open
Our previous study showed that in adult mice, conditional Nedd4-2-deficiency in club and alveolar epithelial type II (AE2) cells results in impaired mucociliary clearance, accumulation of Muc5b and progressive, terminal pulmonary fibrosis …
View article: The common ABCA3<sup>E292V</sup> variant disrupts AT2 cell quality control and increases susceptibility to lung injury and aberrant remodeling
The common ABCA3<sup>E292V</sup> variant disrupts AT2 cell quality control and increases susceptibility to lung injury and aberrant remodeling Open
ATP-binding cassette class A3 (ABCA3) is a lipid transporter that plays a critical role in pulmonary surfactant function. The substitution of valine for glutamic acid at codon 292 (E292V) produces a hypomorphic variant that accounts for a …
View article: Heterogeneity in Human Induced Pluripotent Stem Cell–derived Alveolar Epithelial Type II Cells Revealed with ABCA3/SFTPC Reporters
Heterogeneity in Human Induced Pluripotent Stem Cell–derived Alveolar Epithelial Type II Cells Revealed with ABCA3/SFTPC Reporters Open
Alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, are typically identified through the use of the canonical markers, SFTPC and ABCA3. Self-renewing AEC2-like cells have been generated from human induced…
View article: Congenital Deletion of Nedd4-2 in Lung Epithelial Cells Causes Progressive Alveolitis and Pulmonary Fibrosis in Neonatal Mice
Congenital Deletion of Nedd4-2 in Lung Epithelial Cells Causes Progressive Alveolitis and Pulmonary Fibrosis in Neonatal Mice Open
Recent studies found that expression of NEDD4-2 is reduced in lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and that the conditional deletion of Nedd4-2 in lung epithelial cells causes IPF-like disease in adult mice vi…
View article: Patient-Specific iPSCs Carrying an SFTPC Mutation Reveal the Intrinsic Alveolar Epithelial Dysfunction at the Inception of Interstitial Lung Disease
Patient-Specific iPSCs Carrying an SFTPC Mutation Reveal the Intrinsic Alveolar Epithelial Dysfunction at the Inception of Interstitial Lung Disease Open
The incompletely understood pathogenesis of pulmonary fibrosis (PF) and lack of reliable preclinical disease models have limited development of effective therapies. An emerging literature now implicates alveolar epithelial type 2 cell (AEC…
View article: Role of CCR2+ Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium
Role of CCR2+ Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium Open
Acute inflammatory exacerbations (AIE) represent precipitous deteriorations of a number of chronic lung conditions, including pulmonary fibrosis (PF), chronic obstructive pulmonary disease and asthma. AIEs are marked by diffuse and persist…
View article: Additional file 1 of Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis
Additional file 1 of Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis Open
Additional file 1. Differential protein expression in plasma of IPF patients compared to healthy controls.
View article: Patient-specific iPSCs carrying an<i>SFTPC</i>mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease
Patient-specific iPSCs carrying an<i>SFTPC</i>mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease Open
Summary The incompletely understood pathogenesis of pulmonary fibrosis (PF) and lack of reliable preclinical disease models have limited development of effective therapies. An emerging literature now implicates alveolar epithelial type 2 c…
View article: mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline
mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline Open