A5052141070- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Infant Nutrition and Health
- Neonatal Respiratory Health Research
- Occupational exposure and asthma
- Clinical Nutrition and Gastroenterology
- Autophagy in Disease and Therapy
- Occupational and environmental lung diseases
- RNA modifications and cancer
- Cancer Diagnosis and Treatment
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric Hepatobiliary Diseases and Treatments
- Medical Imaging and Pathology Studies
- Cell Adhesion Molecules Research
- Connective Tissue Growth Factor Research
- Mechanical Circulatory Support Devices
- Child Nutrition and Feeding Issues
- Sirtuins and Resveratrol in Medicine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sphingolipid Metabolism and Signaling
- SARS-CoV-2 and COVID-19 Research
- TGF-β signaling in diseases
- Barrier Structure and Function Studies
- Advanced Glycation End Products research
- Sarcoidosis and Beryllium Toxicity Research
- Metabolism and Genetic Disorders
University of Alabama at Birmingham
2014-2023
Medical University of South Carolina
2021
University of Alabama
2020
Pulmonary and Allergy Associates
2015
Emory University
2011
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.
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...
An immature intestinal epithelial barrier may predispose infants and children to many inflammatory diseases, such as infectious enteritis, bowel disease, necrotizing enterocolitis. Understanding the factors that regulate gut maturation yield insight into strategies prevent these diseases. The claudin family of tight junction proteins plays an important role in regulating paracellular permeability. Previous reports demonstrate rodent function matures during first 3 weeks life. We show murine...
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...
Abstract Matrix stiffening is a prominent feature of pulmonary fibrosis. In this study, we demonstrate that matrix stiffness regulates the ability fibrotic lung myofibroblasts to invade basement membrane (BM). We identify α 6 -integrin as mechanosensing integrin subunit mediates stiffness-regulated myofibroblast invasion. Increasing -expression, specifically B isoform (α B), couples β 1 mediate MMP-2-dependent pericellular proteolysis BM collagen IV, leading Human idiopathic fibrosis express...
Acute lung injury (ALI) is characterized by exuberant proinflammatory responses and mitochondrial dysfunction. However, the link between dysfunction inflammation in ALI not well understood. In this report, we demonstrate a critical role for NAD+-dependent deacetylase, sirtuin-3 (SIRT3), regulating macrophage bioenergetics, ROS formation, responses. We found that SIRT3 expression was significantly diminished lungs of mice subjected to LPS-induced ALI. SIRT3-deficient (SIRT3-/-) develop more...
HDL and its major protein component apolipoprotein A-I (apoA-I) exert anti-inflammatory effects, inhibit monocyte chemotaxis/adhesion, reduce vascular macrophage content in inflammatory conditions. In this study, we tested the hypothesis that apoA-I mimetic 4F modulates function of monocyte-derived macrophages (MDMs) by regulating expression key cell surface receptors on MDMs. Primary human monocytes THP-1 cells were treated with 4F, apoA-I, or vehicle for 7 days analyzed markers, adhesion...
Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics NEC represent common injury response the gastrointestinal tract to variety insults at specific stage gut development. To evaluate developmental changes in mucosal response, used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as...
Matricellular proteins mediate pleiotropic effects during tissue injury and repair. CCN1 is a matricellular protein that has been implicated in angiogenesis, inflammation, wound In this study, we identified as gene differentially up-regulated alveolar mesenchymal cells of human subjects with rapidly progressive idiopathic pulmonary fibrosis (IPF). Elevated levels mRNA were confirmed lung tissues IPF undergoing transplantation, was predominantly localized to fibroblastic foci. expression ex...
Mitochondrial dysfunction has been associated with age-related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein-2 (UCP2), in increased generation reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, induction myofibroblast senescence. This pro-oxidant senescence reprogramming occurs concert conventional actions UCP2 as...
Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Epidermal growth factor (EGF) one the most promising candidates in NEC prophylaxis. Autophagy regulates cell homeostasis, but uncontrolled activation autophagy may lead to cellular injury. The aim was evaluate effects EGF on epithelial cells and rat model measure patients. Intestinal (IEC-6) were used study effect autophagy. Protein levels Beclin 1 LC3II measured epithelium both vivo vitro models....
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...
Macrophages are first seen in the fetal intestine at 11–12 wk and rapidly increase number during 12- to 22-wk period of gestation. The development macrophage populations precedes appearance lymphocytes neutrophils does not require presence dietary or microbial antigens. In this study, we investigated role chemerin, a recently discovered, relatively selective chemoattractant for macrophages, recruitment precursors intestine. Chemerin mRNA/protein expression was measured jejunoileal tissue...
Abstract Organ transplant recipients (OTRs) develop multiple aggressive and metastatic non‐melanoma skin cancers (NMSCs). Yet, the underlying mechanism remains elusive. Employing a variety of immune‐compromised murine models, immunoblotting, immunohistochemical immunofluorescence techniques, we show that human squamous xenograft tumors in nude mice grow faster become significantly larger size following treatment with immunosuppressive drug, cyclosporine A (CsA). Re‐injected tumor cells...
Transforming growth factor-β (TGF-β) mediates growth-inhibitory effects on most target cells via activation of the canonical SMAD signaling pathway. This activity may be coupled with cellular differentiation. Our studies demonstrate that TGF-β1 inhibits proliferation primary, non-transformed human lung fibroblasts in association induction myofibroblast Differentiated myofibroblasts maintain capacity to proliferate response exogenous mitogenic stimuli and are resistant serum...
Neonates and young infants exposed to extracorporeal circulation during membrane oxygenation (ECMO) cardiopulmonary bypass are at risk of developing a systemic inflammatory response syndrome with multi-organ dysfunction. We used piglet model ECMO investigate the hypothesis that epithelial apoptosis is an early event precedes villous damage ECMO-related bowel injury. Healthy 3-week-old piglets were subjected for up 8 h. Epithelial was measured in histopathological analysis, nuclear imaging,...
Alveolar epithelial cell (AEC) injury and apoptosis are prominent pathological features of idiopathic pulmonary fibrosis (IPF). There is evidence AEC plasticity in lung repair response IPF. In this report, we explore the role focal adhesion kinase (FAK) signaling determining fate cells to transforming growth factor-β1 (TGF-β1). Rat type II alveolar (RLE-6TN) were treated with or without TGF-β1, expressions mesenchymal markers, phenotype, function analyzed. Pharmacological protein inhibitors...
Genetic polymorphism along mitochondrial DNA (mtDNA) defines population-specific signatures called mtDNA haplogroups. Estimation of haplogroup distribution may be prone to errors, notably if the study sample is not drawn from a multicenter cohort. Here, we report on diversity in African American individuals (n = 343) enrolled Sequencing hypervariable regions I and II D-loop control region showed that most common variants are 73G, 146C, 150T, 152C, 189G, 16278T, 16311C. In agreement with...
Cross-linking of fibronectin occurs under inflammatory and profibrotic conditions impairs cell migration.