A5035915835- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- Medical Imaging and Pathology Studies
- Telomeres, Telomerase, and Senescence
- Cancer, Hypoxia, and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Advanced biosensing and bioanalysis techniques
- Nitric Oxide and Endothelin Effects
- Ion channel regulation and function
- Autophagy in Disease and Therapy
- Ion Transport and Channel Regulation
- Drug Transport and Resistance Mechanisms
- Pulmonary Hypertension Research and Treatments
- Mesenchymal stem cell research
- Protease and Inhibitor Mechanisms
- Occupational and environmental lung diseases
- Neuroscience of respiration and sleep
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- Infant Nutrition and Health
- Fibroblast Growth Factor Research
- Clusterin in disease pathology
University of Alabama at Birmingham
2013-2022
Pulmonary and Allergy Associates
2014-2021
University of Alabama
2020
London Borough Of Lewisham
2019
Children's Healthcare of Atlanta
2010-2013
Emory University
2010-2013
St. Vincent's Birmingham
2010
University of Iowa
2010
Laboratoire de physiologie cellulaire et moléculaire
2007
Université Côte d'Azur
2003-2005
Fibrosis resolution is impaired by aging and mediated altered cellular redox homeostasis because of a Nox4-Nrf2 imbalance that promotes an apoptosis-resistant myofibroblast phenotype.
Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role metabolic reprogramming is not well appreciated pathogenesis organ fibrosis.
Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics cellular signaling that sustain progressive fibrosis not well defined. In this study, we used ex vivo in approaches define a mechanotransduction pathway Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), coordinately...
Idiopathic pulmonary fibrosis (IPF) is a disease with relentless course and limited therapeutic options. Nintedanib (BIBF-1120) multiple tyrosine kinase inhibitor recently approved by the U.S. Food Drug Administration for treatment of IPF. The precise antifibrotic mechanism(s) action nintedanib, however, not known. Therefore, we studied effects nintedanib on fibroblasts isolated from lungs patients Protein gene expression profibrotic markers were assessed Western immunoblotting real-time...
Contraction is crucial in maintaining the differentiated phenotype of myofibroblasts. an energy-dependent mechanism that relies on production ATP by mitochondria and/or glycolysis. Although role mitochondrial biogenesis adaptive responses skeletal muscle to exercise well appreciated, mechanisms governing energetic adaptation myofibroblasts are not understood. Our study demonstrates induction and aerobic glycolysis response differentiation-inducing factor transforming growth β1 (TGF-β1). This...
Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast has been resistance, mechanisms for this have not well defined. In report, we studied epigenetic involving histone modifications confer resistance senescent human diploid fibroblasts (HDFs). HDFs undergo replicative display typical morphological features, express senescence-associated β-galactosidase, increased levels of the tumor...
Extracellular vesicles (EVs) are endosome and plasma membrane-derived nano-sized that participate in intercellular signaling. Although EV cargo may signal via multiple mechanisms, how signaling components on the surface of EVs mediate cellular is less well understood. In this study, we show fibroblast-derived carry fibronectin vesicular surface, as evidenced by mass spectrometry-based proteomics (Sequential Window Acquisition all Theoretical Mass Spectra) flow-cytometric analyses....
1. Effects of neuropeptides the vasopressin family on Cl(-) secretion have not yet been reported in lung. Using 16HBE14o- bronchial epithelial cell line, we investigated their action secretion. 2. In symmetrical solutions, basolateral application arginine vasotocin (AVT), oxytocin or isotocin induced a transient I(sc) stimulation (I(peak)), whereas (AVP) did not. The effects different channel blockers and protein kinase C (PKC) inhibitor suggest that CFTR is involved I(peak)....
Fibrotic responses involve multiple cellular processes, including epigenetic changes. Epigenetic changes are sensitive to alterations in the tissue microenvironment such as flux of tricarboxylic acid (TCA) cycle metabolites. TCA metabolites directly regulate states, part by regulating histone modification-related enzymes. Glutaminolysis is a critical metabolic process which glutamine converted glutamate glutaminase and then α-ketoglutarate (α-KG), metabolite. Idiopathic pulmonary fibrosis...
Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are essential mediators of salt transport across epithelia. Channel opening normally requires ATP binding to both nucleotide-binding domains (NBDs), probable dimerization the two NBDs, and phosphorylation R domain. How controls channel gating is unknown. Loss-of-function mutations in CFTR gene cause cystic fibrosis; thus, there considerable interest compounds that improve mutant function. Here we investigated...
Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator (CFTR) channel, an ATP binding cassette (ABC) transporter. CFTR gating linked to and dimerization of its two nucleotide domains (NBDs). Channel activation also requires phosphorylation R domain poorly understood mechanisms. Unlike conventional ligand-gated channels, ATPase for which ligand (ATP) release typically involves hydrolysis. The extent conforms classic allosteric schemes unclear. Here, we...
Abstract Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted for regeneration, humans with age-related chronic diseases, such as cancer fibrosis, show evidence recapitulation developmental gene programs. We have previously identified resident population mesenchymal stromal cells (MSCs) the terminal airways-alveoli by bronchoalveolar lavage (BAL) human adult lungs. In this study, we characterized MSCs...
Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). contrast L-MSCs from aged mice, young support efficient formation alveolospheres when co-cultured AEC2s. Aged demonstrated features cellular senescence,...
Significance: Fibrosis is a stereotypic, multicellular tissue response to diverse types of injuries that fundamentally result from failure cell/tissue regeneration. This complex remodeling disrupts cellular/matrix composition and homeostatic cell–cell interactions, leading loss normal architecture progressive organ structure/function. common feature chronic diseases may affect the lung, kidney, liver, heart. Recent Advances: There emerging evidence support combination genetic, environmental,...
Cystic fibrosis (CF) is caused by loss-of-function mutations in the CFTR chloride channel. Wild type and mutant channels can be activated curcumin, a well tolerated dietary compound with some appeal as prospective CF therapeutic. However, we show here that curcumin has unexpected effect of cross-linking polypeptides into SDS-resistant oligomers. This occurred for microsomes intact cells at same concentrations are effective promoting channel activity (5–50 μm). Both mature cell surface...
Excessive extra-cellular-matrix production and uncontrolled proliferation of the fibroblasts are characteristics many fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). The have enhanced glutaminolysis with up-regulated glutaminase, GLS1, which converts glutamine to glutamate. Here, we investigated role glutaminolysis-derived metabolite α-ketoglutarate (α-KG) on IPF fibroblast phenotype gene expression. Reduced conditions were carried out either using glutamine-free culture...
Cross-linking of fibronectin occurs under inflammatory and profibrotic conditions impairs cell migration.