A5045287232- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tissue Engineering and Regenerative Medicine
- Electrospun Nanofibers in Biomedical Applications
- Pulmonary Hypertension Research and Treatments
- Hippo pathway signaling and YAP/TAZ
- Neonatal Respiratory Health Research
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Connective Tissue Growth Factor Research
- Electrohydrodynamics and Fluid Dynamics
- Respiratory Support and Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Occupational and environmental lung diseases
- Fibroblast Growth Factor Research
- Tracheal and airway disorders
- Retinal Diseases and Treatments
- Circular RNAs in diseases
- Molecular Biology Techniques and Applications
- Cardiovascular Effects of Exercise
- Mesenchymal stem cell research
- Statistical Methods in Clinical Trials
- Angiogenesis and VEGF in Cancer
- Periodontal Regeneration and Treatments
Mayo Clinic in Florida
2021-2024
Mayo Clinic
2020-2024
WinnMed
2020-2023
Virginia Commonwealth University
2016-2023
Mayo Clinic in Arizona
2020
University of California, Berkeley
1991
The complexity and rapid clearance mechanisms of lung tissue make it difficult to develop effective treatments for many chronic pathologies. We are investigating derived extracellular matrix (ECM) hydrogels as a novel approach delivery cellular therapies the pulmonary system. main objectives this study include decellularization porcine tissue, development hydrogel from ECM, characterization material's composition, mechanical properties, ability support growth. Our evaluation decellularized...
Hydrogels derived from decellularized lungs are promising materials for tissue engineering in the development of clinical therapies and modeling lung extracellular matrix (ECM) vitro. Characterizing controlling resulting physical, biochemical, mechanical, biologic properties ECM (dECM) after enzymatic solubilization gelation thus key interest. As role pepsin digestion effecting these has been understudied, we investigated time-dependency on parameters hydrogel. Using resolubilized,...
Abstract Vascular dysfunction is a hallmark of chronic diseases in elderly. The contribution the vasculature to lung repair and fibrosis not fully understood. Here, we performed an epigenetic transcriptional analysis endothelial cells (ECs) from young aged mice during resolution or progression bleomycin-induced fibrosis. We identified transcription factor ETS-related gene (ERG) as putative orchestrator capillary homeostasis repair, whose function dysregulated aging. ERG dysregulation...
Fibroblast activation is transient in successful wound repair but persistent fibrotic pathologies. Understanding fibroblast deactivation during healing may provide new approaches to therapeutically reverse activation. To characterize the gene programs that accompany and reversal lung fibrosis resolution, we used RNA sequencing analysis of flow sorted Col1α1-GFP–positive CD45-, CD31-, CD326-negative cells isolated from lungs young mice exposed bleomycin. We compared fibroblasts control with...
Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix to changes in phenotype are incompletely understood. Here, we evaluated effect on genome-wide chromatin accessibility freshly isolated lung fibroblasts using ATAC-seq. We found higher profoundly increased global relative lower stiffness, and these alterations were close genomic proximity known profibrotic gene programs. Motif analysis regulated loci identified ZNF416 as...
Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are transcription cofactors implicated in the contractile profibrotic activation of fibroblasts. Fibroblast function is important alveologenesis lung wound healing fibrosis. As paralogs, YAP TAZ may have independent or redundant roles regulating programs function. Using IMR-90 fibroblasts, microarray analysis, traction microscopy, we tested whether knockdown alone was sufficient to limit contraction...
Here we present a method for establishing multiple component cell culture hydrogels in vitro lung culture. Beginning with healthy en bloc tissue from porcine, rat, or mouse, the is perfused and submerged subsequent chemical detergents to remove cellular debris. Histological comparison of before after processing confirms removal over 95% double stranded DNA alpha galactosidase staining suggests majority debris removed. After decellularization, lyophilized then cryomilled into powder. The...
Matrix resorption is essential to the clearance of extracellular matrix (ECM) after normal wound healing. A disruption in these processes constitutes a main component fibrotic diseases, characterized by excess deposition and diminished fibrillar ECM proteins, such as collagen type I. The mechanisms stimuli regulating lung remain poorly understood. Recently, agonism dopamine receptor D1 (DRD1), which predominantly expressed on fibroblasts lung, has been shown accelerate tissue repair...
Yes-associated protein (YAP) and PDZ-binding motif (TAZ) have emerged as important regulators of pathologic fibroblast activation in fibrotic diseases. Agonism Gαs-coupled G coupled receptors (GPCRs) provides an attractive approach to inhibit the nuclear localization function YAP TAZ fibroblasts that inhibits or reverses their pathological activation. dopamine D1 GPCR has proven effective preclinical models lung liver fibrosis. However, molecular mechanisms coupling agonism inactivation...
Here we present a method for establishing multiple component cell culture hydrogels in vitro lung culture. Beginning with healthy en bloc tissue from porcine, rat, or mouse, the is perfused and submerged subsequent chemical detergents to remove cellular debris. Histological comparison of before after processing confirms removal over 95% double stranded DNA alpha galactosidase staining suggests majority debris removed. After decellularization, lyophilized then cryomilled into powder. The...
Decellularized extracellular matrix (ECM) is an effective tissue repair scaffold. Additionally, ECM has recently been shown to be protective the lungs. However, current processing inadequate for delivery of Processing methods, such as milling, produce large variability in particle sizes. The size variation produced ineffective at treating lung because only a small range sizes reach distal regions alveoli. aim this work formulate decellularized while retaining pro-regenerative effects ECM. We...
Retinal pigmented epithelial (RPE) cells play an important role in retinal fibrotic diseases such as proliferative vitreoretinopathy (PVR). The purpose of this study was to elucidate the involvement dopamine receptor signaling regulating activation RPE cells. Dopamine expression, effect on activity, and production were measured human cell line ARPE-19. evaluated response treatments with selective agonists antagonists by measuring gene migration, proliferation, fibronectin deposition. DRD2...
Abstract Pulmonary arterial hypertension (PAH) causes pulmonary vascular remodeling, increasing resistance (PVR) and leading to right heart failure death. Matrix stiffening early in the disease promotes remodeling artery smooth muscle cells (PASMCs), contributing PAH pathogenesis. Our research identified YAP TAZ as key drivers of mechanobiological feedback loop PASMCs, suggesting targeting them could mitigate remodeling. However, YAP/TAZ are ubiquitously expressed carry out diverse...
Abstract Pulmonary arterial hypertension (PAH) is a progressive, devastating disease, and its main histological manifestation an occlusive pulmonary arteriopathy. One important functional component of PAH aberrant endothelial cell (EC) function including apoptosis‐resistance, unchecked proliferation, impaired migration. The mechanisms leading to maintaining physiologic EC are not fully understood. Here, we tested the hypothesis that in PAH, ECs have increased expression transmembrane protein...
Pulmonary fibroblasts are the primary producers of extracellular matrix (ECM) in lungs, and their pathogenic activation drives scarring loss lung function idiopathic pulmonary fibrosis (IPF). This uncontrolled production ECM is stimulated by mechanosignaling TGF-β1 signaling which together promote transcriptional programs including Yes-associated protein (YAP) coactivator with PDZ-binding motif (TAZ). G protein-coupled receptors couple to alpha s have emerged as pharmacological targets...
A cell culture system has been developed that produces stable gastrointestinal (GI) polarized lines capable of maintaining hormone secretion. spontaneously transformed rat mucosal epithelial was selected for hypoxanthine/guanine phosphoribosyltransferase deficiency and transfected with a plasmid conferring hygromycin resistance (BRIE 291 cells). Fusion these cells dispersed small intestinal epithelia resulted in hybrid retained characteristic properties the native GI more effectively than...
Pulmonary arterial hypertension has characteristic changes to the mechanical environment, extracellular matrix, and cellular proliferation. In order develop a culture system investigate matrix (ECM) compositional-dependent in pulmonary hypertension, we decellularized characterized protein lipid profiles from healthy Sugen-Chronic Hypoxia rat lungs. Significant were observed intact Sugen-Hypoxia lungs compared with controls. Decellularized lung retained lipids measurable quantities both...
Aberrant vascular remodeling contributes to the progression of many aging-associated diseases, including idiopathic pulmonary fibrosis (IPF), where heterogeneous capillary density, endothelial transcriptional alterations, and increased permeability correlate with poor disease outcomes. Thus, identifying disease-driving mechanisms in vasculature may be a promising strategy limit IPF progression. Here, we identified
Idiopathic pulmonary fibrosis (IPF) is an aggressive and, thus far, incurable disease characterized by aberrant fibroblast-mediated extracellular matrix deposition. Our understanding of the etiology incomplete; however, there consensus that a reduction-oxidation (redox) imbalance plays role. In this study, we use autofluorescent properties two redox molecules, NAD(P)H and FAD, to quantify changes in their relative abundance living lung tissue mice with experimental freshly isolated cells...
Abstract Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix to changes in phenotype are incompletely understood. Here, we evaluated effect on genome-wide chromatin accessibility freshly-isolated lung fibroblasts using assay for transposase-accessible followed by sequencing (ATAC-seq). We found higher profoundly increased global relative lower stiffness, and these alterations were close genomic proximity known pro-fibrotic...