A5051159353- Sphingolipid Metabolism and Signaling
- Extracellular vesicles in disease
- Hearing, Cochlea, Tinnitus, Genetics
- Autophagy in Disease and Therapy
- Marine animal studies overview
- MicroRNA in disease regulation
- Complement system in diseases
- Neonatal Respiratory Health Research
- Erythrocyte Function and Pathophysiology
- Lysosomal Storage Disorders Research
- Respiratory Support and Mechanisms
- Proteoglycans and glycosaminoglycans research
- Mesenchymal stem cell research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cytokine Signaling Pathways and Interactions
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Inhalation and Respiratory Drug Delivery
- Autoimmune and Inflammatory Disorders Research
- Air Quality and Health Impacts
- Immune cells in cancer
- Antimicrobial Peptides and Activities
- Hemoglobin structure and function
- Acoustic Wave Phenomena Research
National Jewish Health
2016-2023
University of Colorado Denver
2016-2023
Indiana University School of Medicine
2013-2016
Indiana University
2016
Indiana University – Purdue University Indianapolis
2013-2016
Abstract Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism release and function remain unknown. We assessed biochemical functional characteristics EMPs circulating (cMPs) released by CS. CS exposure was sufficient increase microparticle levels plasma humans mice supernatants primary human lung microvascular cells. CS-released contained predominantly...
Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian do not regenerate and are limited in number. Here we investigate potential generate from mouse embryonic stem a three-dimensional (3D) culture system. The system faithfully recapitulates inner induction followed by self-guided development into organoids morphologically resemble vestibular organs. We find organoid acquire mechanosensitivity...
MicroRNA-126-3p (miR-126) is required for angiogenesis during organismal development or the repair of injured arterial vasculature. The role miR-126 in lung microvascular endothelial cells, which are essential gas exchange and injury regeneration, remains poorly understood. Considering significant heterogeneity cells from different vascular beds, we aimed to determine regulating cell function elucidate its downstream signaling pathways. Approach Results: Overexpression knockdown primary...
Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens. This global deficit AM engulfment may explain why active smokers have worse outcomes exacerbations, episodes characterized by airway infection inflammation that carry high morbidity healthcare cost. When administered as intravenous supplementation, acute phase-reactant alpha-1...
The loss of pulmonary endothelial cells in emphysema is associated with increased lung ceramide. Ceramide perturbations may cause adaptive alterations other bioactive sphingolipids, pathogenic implications. We previously reported a negative correlation between and circulating glycosphingolipids (GSLs). Glucosylceramide (GlcCer), the initial GSL synthesized from ceramide by GCS (GlcCer synthase), required for embryonic survival, but its role unknown.
Several inflammatory lung diseases display abundant presence of hyaluronic acid (HA) bound to heavy chains (HC) serum protein inter-alpha-inhibitor (IαI) in the extracellular matrix. The HC-HA modification is critical neutrophil sequestration liver sinusoids and survival during experimental lipopolysaccharide (LPS)-induced sepsis. Therefore, covalent binding, which exclusively mediated by tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6), may play an important role onset or resolution...
Studies of chronic obstructive pulmonary disease (COPD) using animal models and patient plasma indicate dysregulation sphingolipid metabolism, but data in COPD lungs are sparse. Mass spectrometric immunostaining measurements from 69 COPD, 16 smokers without 13 subjects with interstitial lung identified decoupling ceramide sphingosine-1 phosphate (S1P) levels decreased sphingosine kinase-1 (SphK1) activity COPD. The correlation abundance distal apoptosis the inverse between SphK1 presence...
Deficiency of ASM (acid sphingomyelinase) causes the lysosomal storage Niemann-Pick disease (NPD). Patients with NPD type B may develop progressive interstitial lung frequent respiratory infections. Although several investigations using ASM-deficient (ASMKO) mouse model revealed inflammation and foamy macrophages, there is little insight into pathogenesis NPD-associated disease. Using ASMKO mice, we report that deficiency associated a complex inflammatory phenotype characterized by marked...
Chronic obstructive pulmonary disease (COPD) is characterized by nonresolving inflammation fueled breach in the endothelial barrier and leukocyte recruitment into airspaces. Among ligand-receptor axes that control recruitment, full-length fractalkine ligand (CX3CL1)-receptor (CX3CR1) ensures homeostatic endothelial-leukocyte interactions. Cigarette smoke (CS) exposure respiratory pathogens increase expression of sheddases, such as a-disintegrin-and-metalloproteinase-domain 17 (ADAM17, TACE),...
Proapoptotic and monocyte chemotactic endothelial monocyte-activating protein 2 (EMAPII) is released extracellularly during cigarette smoke (CS) exposure. We have previously demonstrated that, when administered intratracheally chronic CS exposures, neutralizing rat antibodies to EMAPII inhibited cell apoptosis lung inflammation reduced airspace enlargement in mice (DBA/2J strain). Here we report further preclinical evaluation of targeting using anti-EMAPII via either nebulization or...
RationaleThe clinical syndrome associated with SARS-CoV2, known as COVID-19 is characterized by a spectrum of hypercoagulability and complement-mediated microvascular injury in severe but also mild disease(1-4). Studies have demonstrated that lectin complement pathway (driven MBL/MASP2 complex) responsible for the via MBL binding SARS-CoV virion(5) deposition MBL, MASP-2, C4 seen skin lung specimens individuals, where SARS-CoV-2 spike protein (SP) co-localized C4(4, 6). We hypothesize...
RATIONALE: Niemann-Pick disease (A and B), caused by SMPD1 gene mutations is characterized progressive often fatal multiple organ dysfunction, including interstitial lung disease.SMPD1 encodes acid sphingomyelinase (ASM), an essential lysosomal enzyme that catabolizes sphingomyelin to ceramide.Previous studies of ASM deficient (ASMKO) mice, a model NPD, revealed age-dependent inflammation with increased foamy macrophages monocyte-chemoattractant cytokines.Nonetheless, the pathobiology...