A5001589979- Dermatology and Skin Diseases
- Food Allergy and Anaphylaxis Research
- Sphingolipid Metabolism and Signaling
- Allergic Rhinitis and Sensitization
- Urticaria and Related Conditions
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Contact Dermatitis and Allergies
- Eosinophilic Esophagitis
- Advancements in Transdermal Drug Delivery
- Exercise and Physiological Responses
- Long-Term Effects of COVID-19
- Lysosomal Storage Disorders Research
- Lipid Membrane Structure and Behavior
- Pharmacological Effects of Natural Compounds
- Caveolin-1 and cellular processes
- Skin Protection and Aging
- Asthma and respiratory diseases
- Liver physiology and pathology
- Eosinophilic Disorders and Syndromes
- Cellular transport and secretion
- Psoriasis: Treatment and Pathogenesis
- Heme Oxygenase-1 and Carbon Monoxide
- Neonatal Respiratory Health Research
- Fibroblast Growth Factor Research
National Jewish Health
2016-2025
University of Colorado Denver
2016-2025
University of Illinois Chicago
2016-2021
Lipids in the stratum corneum of atopic dermatitis (AD) patients differ substantially composition from healthy subjects. We hypothesized that hyperactivated type 2 immune response alters AD skin lipid metabolism. have analyzed lipids nonlesional and lesional subjects IL-13 skin-specific Tg mice. also directly examined effects IL-4/IL-13 on human keratinocytes vitro. Mass spectrometric analysis mice revealed an increased proportion short-chain (N-14:0 to N-24:0) NS ceramides, sphingomyelins,...
Patients with atopic dermatitis and food allergy have an immature epithelial barrier type 2 immune activation in their skin.
Abstract Background Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven hyperactivated type 2 immune responses. The antibody to the α‐subunit of interleukin (IL)‐4 receptor, dupilumab, was recently approved treat AD and demonstrated strong efficacy. However, role dupilumab therapy in regulation barrier structure function has not been fully explored. Methods We have evaluated content transepidermal water loss (TEWL) lesional non‐lesional adults adolescents...
The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, PM2.5 filaggrin (FLG) and were investigated in vitro vivo. levels FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), cis/trans-UCA, significantly decreased tape stripping samples study subjects when they moved from Denver, an area with low PM2.5, to Seoul, high count. Experimentally, collected Seoul...
Abstract Background Staphylococcus ( S ) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how . induces aberrant epidermal lipid composition and dysfunction. Methods Skin tape strips (STS) swabs were obtained from 24 children with AD (6.0 ± 4.4 years) 16 healthy (7.0 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. levels methicillin‐sensitive methicillin‐resistant (MSSA MRSA)...
The mechanisms by which lung structural cells survive toxic exposures to cigarette smoke (CS) are not well defined but may involve proper disposal of damaged mitochondria macro-autophagy (mitophagy), processes that be influenced pro-apoptotic ceramide (Cer) or its precursor dihydroceramide (DHC). Human epithelial and endothelial exposed CS exhibited mitochondrial damage, signaled phosphatase tensin homolog-induced putative kinase 1 (PINK1) phosphorylation, autophagy, necroptosis. Although...
Introduction Dysregulated sphingolipid metabolism has been implicated in the pathogenesis of various pulmonary disorders. Nuclear sphingosine-1-phosphate (S1P) shown to regulate histone acetylation, and therefore could mediate pro-inflammatory genes expression. Methods Profile species bronchoalveolar lavage fluids lung tissue mice challenged with Pseudomonas aeruginosa ( PA ) was investigated. The role nuclear sphingosine kinase (SPHK)2 S1P inflammatory injury by using genetically engineered...
Lysophosphatidic acid (LPA) is an important mediator of pulmonary fibrosis. In blood and multiple tumor types, autotaxin produces LPA from lysophosphatidylcholine (LPC) via lysophospholipase D activity, but alternative enzymatic pathways also exist for production. We examined the role (ATX) in production during fibrogenesis a bleomycin mouse model. found that injury increases bronchoalveolar lavage (BAL) fluid levels ATX protein 17-fold. However, LPC species increase BAL bleomycin-injured...
The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear. Implicated in pathophysiology diverse diseases characterized by endothelial damage, including ARDS and ischemic cardiovascular disease, ceramide particular palmitoyl (C16:0-ceramide) may be involved microvascular injury COVID-19. Using deidentified plasma lung samples from patients, profiling mass spectrometry was performed....
Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation of human lung microvascular cells (HLMVECs) PI3K/Akt signal transduction reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), receptor, S1P1, in...
Skin lipids are crucial components of the skin barrier. Individuals with atopic dermatitis (AD or eczema) have a different lipid profile from those without. However, whether altered precede and predict subsequent risk AD remained unclear, especially for phenotypes. We sought to examine relationship between phenotypes in infants. forearms 133 infants family history allergic disease were sampled using tape strips at age 6 weeks. Lipids quantified liquid chromatography-tandem mass spectrometry....
Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated autophagy. We set out to investigate role baseline ASM activity maintaining physiological functions lysosomes, focusing on nutrient-sensing complex (LYNUS), a membrane-anchored multiprotein that includes mammalian target rapamycin (mTOR) transcription factor EB (TFEB). inhibition with imipramine or sphingomyelin phosphodiesterase...
Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution the endocannabinoid signaling system in fibrogenesis not known. Using well-established mouse model RIF, we assessed involvement cannabinoid receptor-1 (CB1) onset progression fibrosis. Female C57BL/6 mice CB1 knockout generated on background received 20 Gy (2 Gy/min) single-dose irradiation resulted animal death within 15 to 18 weeks....
Mechanical ventilation (MV) performed in respiratory failure patients to maintain lung function leads ventilator-induced injury (VILI). This study investigates the role of sphingolipids and sphingolipid metabolizing enzymes VILI using a rodent model alveolar epithelial cells subjected cyclic stretch (CS). MV (0 PEEP (Positive End Expiratory Pressure), 30 mL/kg, 4 h) mice enhanced sphingosine-1-phosphate lyase (S1PL) expression, ceramide levels, decreased S1P levels tissue, thereby leading...
Activation of hepatic stellate cells (HSCs) in response to injury is a key step fibrosis, and characterized by trans-differentiation quiescent HSCs HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies directly inhibit fibrosis. We developed small molecule screen identify compounds that inactivate human myofibroblasts through quantification lipid droplets. screened 1600 identified 21 molecules induce inactivation....
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.