A5052181964- Immune Response and Inflammation
- Asthma and respiratory diseases
- Genomics, phytochemicals, and oxidative stress
- Immune cells in cancer
- Extracellular vesicles in disease
- NF-κB Signaling Pathways
- Sirtuins and Resveratrol in Medicine
- IL-33, ST2, and ILC Pathways
- Signaling Pathways in Disease
- Neonatal Respiratory Health Research
- Inflammasome and immune disorders
- MicroRNA in disease regulation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Pulmonary Hypertension Research and Treatments
- Circular RNAs in diseases
- Air Quality and Health Impacts
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Heme Oxygenase-1 and Carbon Monoxide
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Renal and related cancers
- PARP inhibition in cancer therapy
The Ohio State University Wexner Medical Center
2014-2025
The Ohio State University
2014-2025
University of Illinois Chicago
2013
University of Rochester Medical Center
2009-2012
University of Rochester
2010
Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD+-dependent protein/histone deacetylase, reduced in lungs of patients with COPD. However, the molecular signals underlying aging lungs, whether SIRT1 protects against cellular senescence various pathophysiological alterations emphysema, remain unknown. Here, we showed increased COPD patients. activation both genetic...
Sirtuinl (SIRT1) deacetylase levels are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. We determined the mechanism of SIRT1 redox post-translational modifications leading to its degradation. Human lung epithelial cells exposed hydrogen peroxide (150–250 µM), aldehyde-acrolein (10–30 cigarette smoke extract (CSE;0.1–1.5%) presence intracellular glutathione-modulating agents at 1–24 h, were assayed cells, as well lungs mice lacking overexpressing...
Extracellular superoxide dismutase (ECSOD or SOD3) is highly expressed in lungs and functions as a scavenger of O(2)(*-). ECM fragmentation, which can be triggered by oxidative stress, participates the pathogenesis chronic obstructive pulmonary disease (COPD) through attracting inflammatory cells into lungs. The level SOD3 significantly decreased patients with COPD. However, role endogenous development/progression emphysema unknown. We hypothesized that protects against attenuating...
Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal study was define mechanisms that control AM phenotypic and functional response acute allergic airway inflammation. phenotype characteristics AMs obtained human subjects after subsegmental bronchoprovocation allergen studied. Using macrophage-depleted mice, role...
Forkhead box class O 3a (FOXO3) is a member of the FoxO transcription factor subfamily, which regulates expression target genes not only through DNA binding as factor, but also protein-protein interaction. Although FoxO3 well-known involved in diverse biological processes, role cigarette smoke (CS)-induced lung inflammation and injury has been studied. It is, therefore, hypothesized that deficiency leads to increased susceptibility CS-induced inflammatory response airspace enlargement. In...
Rationale: Bioactive lipid mediators, derived from membrane precursors, are released into the airway and airspace where they bind high-affinity cognate receptors may mediate asthma pathogenesis. Lysophosphatidic acid (LPA), a bioactive mediator generated by enzymatic activity of extracellular autotaxin (ATX), binds LPA receptors, resulting in an array biological actions on cell proliferation, migration, survival, differentiation, motility, therefore could pathogenesis.Objectives: To define...
The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role alternatively activated (AAM) asthmatic inflammation has yet been investigated. Here we report that serves as a critical regulator AAM polarization promotes pathological progress airway inflammation. In response to challenge DRA (dust mite, ragweed, Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic inflammation, including...
Abstract Macrophages are a heterogeneous population of immune cells that essential for the initiation and containment inflammation. There 2 well-established populations inflammatory macrophages: classically activated M1 alternatively M2 macrophages. The FoxO family transcription factors plays key roles in number cellular processes, including cell growth, metabolism, survival, In this study, we determined whether expression FoxO1 contributes polarization macrophages toward M2-like phenotype...
Abstract Renal tubular epithelial cells (RTECs) perform the essential function of maintaining constancy body fluid composition and volume. Toxic, inflammatory, or hypoxic-insults to RTECs can cause systemic imbalance, electrolyte abnormalities metabolic waste accumulation- manifesting as acute kidney injury (AKI), a common disorder associated with adverse long-term sequelae high mortality. Here we report results kinome-wide RNAi screen for cellular pathways involved in AKI-associated...
// Sangwoon Chung 1 , Tae Jin Lee 2 Brenda F. Reader Ji Young Kim Yong Gyu Gye Park 3 Manjula Karpurapu Megan N. Ballinger Feng Qian Luiza Rusu Hae 4 Terry G. Unterman 5 Carlo M. Croce and John W. Christman Pulmonary, Allergy, Critical Care Sleep Medicine, Ohio State University Wexner Medical Center, Davis Heart Lung Research Institute, Columbus, Ohio, USA Department of Molecular Virology, Immunology Genetics Comprehensive Cancer University, Section Care, Illinois at Chicago, Illinois,...
Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that aberrantly regulated cancer cells. This study aimed to determine therapeutic potential putative tumor miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one significantly downregulated miRNAs with an inverse correlation CD44 expression. Transient...
Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role CS-induced pro-inflammatory gene transcription by chromatin modifications; however, underlying downstream signaling not known. Mitogen- and stress-activated 1 (MSK1) serves as specific NF-κB RelA/p65 kinase, mediating transcriptional activation NF-κB-dependent...
Nuclear factor (NF)-κB inducing kinase (NIK) is a central player in the non-canonical NF κB pathway, which phosphorylates IκB α (IKKα) resulting enhancement of target gene expression. We have recently shown that IKKα responds to variety stimuli including oxidants and cigarette smoke (CS) regulating histone modification addition its role NF-κB activation. However, primary signaling mechanism linking CS-mediated oxidative stress TNFα with acetylation pro-inflammatory transcription not well...
Abstract Background The pathogenesis of asthma and airway obstruction is the result an abnormal response to different environmental exposures. scientific premise our study was based on finding that FoxO1 expression increased in lung macrophages mice after allergen exposure human asthmatic patients. Macrophages are capable switching from one functional phenotype another, it important understand mechanisms involved transformation how their cellular function affects peribronchial stromal...
NF-κB-mediated proinflammatory response to cigarette smoke (CS) plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The heterodimer RelA/p65-p50 (subunits NF-κB) is involved transactivation NF-κB-dependent genes, but interestingly p50 has no domain. endogenous subunit, particularly regulation CS-mediated inflammation vivo, not known. We therefore hypothesized that subunit regulatory on RelA/p65, and genetic ablation (p50 −/− ) leads increased lung...
Glutaredoxin 1 (Glrx1) is a small dithiol protein that regulates the cellular redox state and redox-dependent signaling pathways via modulation of glutathionylation. IkappaB kinase (IKK), an essential enzyme for NF-kappaB activation, can be subjected to S-glutathionylation leading alteration its activity. However, role Glrx1 in cigarette smoke (CS)-induced lung inflammation chromatin modifications are not known. We hypothesized CS-induced differential regulation IKKs by mouse lung. knockout...
Allergic eosinophilic asthma is a chronic condition causing airway remodeling resulting in lung dysfunction. We observed that expression of sirtuin 2 (Sirt2), histone deacetylase, regulates the recruitment eosinophils after sensitization and challenge with triple antigen: dust mite, ragweed, Aspergillus fumigatus (DRA). Our data demonstrate IL-4 Sirt2 isoform 3/5. Pharmacological inhibition by AGK2 resulted diminished cellular recruitment, decreased CCL17/TARC, reduced goblet cell...
Mitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, is linked to nuclear methylation gene expression. Increased mtCN in the blood associated with smoking respiratory disease, but has received little attention for target organ effects or electronic cigarette (EC) use.Bronchoscopy biospecimens from healthy EC users, smokers (SM), never-smokers (NS) were assessed associations of mtDNA point mutations, immune responses, expression using linear regression. Ingenuity...