A5036151111- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- Respiratory viral infections research
- Medical Imaging and Pathology Studies
- Influenza Virus Research Studies
- IL-33, ST2, and ILC Pathways
- Bone health and treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Respiratory and Cough-Related Research
- Eosinophilic Esophagitis
- Antimicrobial Peptides and Activities
- Parathyroid Disorders and Treatments
- Tracheal and airway disorders
- Bone and Dental Protein Studies
- Fibroblast Growth Factor Research
- Occupational and environmental lung diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Biomarkers in Disease Mechanisms
- Pediatric health and respiratory diseases
- Immune Response and Inflammation
- Ion Transport and Channel Regulation
- Adenosine and Purinergic Signaling
- Bone Metabolism and Diseases
- Hemoglobin structure and function
University of Cincinnati
2005-2024
University of Cincinnati Medical Center
2005-2023
Washington University in St. Louis
2021
Cincinnati Children's Hospital Medical Center
2003-2006
ENT and Allergy
2004
Abbott Fund
1999
Pulmonary eosinophilia, a hallmark pathologic feature of allergic lung disease, is regulated by interleukin-13 (IL-13) as well the eotaxin chemokines, but specific role these cytokines and their cooperative interaction are only partially understood. First, we elucidated essential IL-13 in induction eotaxins comparing gene-targeted mice with wild type control using an ovalbumin-induced model airway inflammation. Notably, expressions eotaxin-1 eotaxin-2 mRNA lungs were almost completely...
The analysis of polygenic diseases such as asthma poses a challenging problem. In an effort to provide unbiased insight into disease pathogenesis, we took empirical approach involving transcript expression profiling lung tissue from mice with experimental asthma. Asthmatic responses were found involve sequential induction 4.7% the tested genome; notably, there was ectopic series genes not previously implicated in allergic or pulmonary responses. Genes widely distributed throughout all...
IL-13 overexpression in the lung induces inflammatory and remodeling responses that are prominent features of asthma. Whereas most studies have concentrated on development IL-13-induced disease, far fewer focused reversibility pathologies. This is particularly important because current asthma therapy appears to be poor at reversing remodeling. In this manuscript, we used an externally regulatable transgenic system targets expression with aim characterizing process. After 4 wk doxycycline...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Resistin-like molecule (RELM)-beta is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-beta has role promoting airway inflammation lung remodeling the mouse lung. strongly induced by diverse allergens T helper type 2 (Th2) cytokines IL-13- STAT6-dependent mechanism. To understand vivo of RELM-beta, we delivered recombinant murine intratracheally to naïve mice. dose-dependent leukocyte accumulation...
Epithelial deletion of Npt2b results in a tractable mimic pulmonary alveolar microlithiasis.
Asthma is a complex inflammatory pulmonary disorder that on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered involvement two members small proline-rich protein (SPRR) family, SPRR2a SPRR2b, known be epithelial differentiation but not allergic disease. In situ hybridization revealed induction SPRR2 signal subset bronchial...
Significance Influenza is a recurring global health threat that preferentially targets vulnerable groups such as the very young, pregnant, elderly, and infirm. The spread of influenza A virus (IAV) from epithelium conducting airway to alveolar pivotal event in pathogenesis primary viral pneumonia. Host susceptibility IAV pneumonia often attributed altered immunity, cell autonomous vulnerability states epithelium, proliferative tone, are rarely considered. Here we demonstrate mitogenic...
Abstract Traumatic injury is generally considered to have a suppressive effect on the immune system, resulting in increased susceptibility infection. Paradoxically, we found that thermal skin induced robust time-dependent protection of mice from lethal Klebsiella pneumoniae pulmonary challenge. The protective response was neutrophil dependent and temporally associated with systemic increase neutrophils reprioritization hematopoiesis toward myeloid lineages. A prominent specific activation...
Abstract Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results accumulation of phosphate and formation hydroxyapatite microliths space. The single cell transcriptomic analysis explant showing robust osteoclast gene signature monocytes finding calcium contain rich protein lipid matrix includes bone resorbing enzymes other proteins suggested role for osteoclast-like cells...
The Ron receptor tyrosine kinase (TK) plays a regulatory role in the inflammatory response to acute lung injury induced by intranasal administration of bacterial LPS. Previously, we have shown that mice with targeted deletion TK signaling domain exhibited more severe LPS as evidenced an increased leakage albumin lungs and greater thickening alveolar septa compared wild-type mice. In addition, TK-deficient (TK(-/-)) was associated activation transcription factor, nuclear factor-kappaB...
The recognition of influenza A virus (IAV) by surfactant protein D (SP-D) is mediated interactions between the SP-D carbohydrate domains (CRD) and glycans displayed on envelope glycoproteins. Although native human shows potent antiviral aggregating activity, trimeric recombinant neck+CRDs (NCRDs) show little or no capacity to influence IAV infection. mutant NCRD, D325A/R343V, showed marked hemagglutination inhibition viral neutralization, with aggregation aggregation-dependent uptake...
Asthma, a complex chronic inflammatory pulmonary disorder, is on the rise despite intense ongoing research, underscoring need for new scientific inquiry. In an effort to provide unbiased insight into pathogenesis of this disease, we took empirical approach involving transcript expression profiling lung tissue from mice with experimental asthma. Employing asthma models induced by different allergens (ovalbumin [OVA] and Aspergillus fumigatus), found strong induction trefoil factor-2 (TFF2),...
Keratinocyte growth factor (KGF) is an epithelial mitogen that has been reported to protect the lungs from a variety of toxic and infectious insults. In prior studies we found recombinant human KGF accelerates clearance bacteria murine lung by augmenting function alveolar macrophages (AM). this study tested hypothesis endogenous plays role in maintenance innate pulmonary defense against gram-negative bacterial infections. KGF-deficient mice exhibited delayed Escherichia coli lungs,...
The pathophysiology of silicosis is poorly understood, limiting development therapies for those who have been exposed to the respirable particle. We explored mechanisms silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure silica and a longitudinal mouse model using multiple modalities including whole-lung single-cell RNA sequencing histological, biochemical, physiologic assessments. In addition inflammation fibrosis, intratracheal...
We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), host defense lectin, with combinatorial substitutions at the 325 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains influenza A virus (IAV). The NCRD binds to glycan-rich viral envelope proteins including hemagglutinin (HA). now show replacement D325 serine create D325S+R343V provided equal or neutralizing compared...
Abstract The pathophysiology of silicosis is poorly understood, limiting development therapies for those who have been exposed to the respirable particle. We explored mechanisms silica-induced pulmonary fibrosis in a mouse model using multiple modalities including wholelung single-nucleus RNA sequencing. These analyses revealed that addition inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation alveolar macrophages recruited monocytes, driven by...
Previous studies have shown that the Ron receptor tyrosine kinase is an important regulator of acute lung inflammatory response induced by intranasal administration bacterial LPS. Compared to wild-type mice, complete loss in all cell types vivo was associated with increased damage as determined histological analyses and several markers injury including increases pro-inflammatory cytokines such TNF-α. Tumor-necrosis factor-α a multifunctional cytokine secreted macrophages, which plays major...
Asthma is a complex pulmonary disorder characterized by reversible airflow obstruction, airway hyperresponsiveness, mucus cell metaplasia, and inflammation. Employing animal models of inflammation induced different allergens Th2 cytokines, the authors have previously described up-regulation trefoil factor 2 (TFF2) in lung. Given known biological role factors epithelial restitution, it has been postulated that allergen-induced TFF2 might an important asthmatic responses. Here show early...
Lung surfactant proteins (SPs) play critical roles in function and innate immunity. SP-A SP-D, members of the collectin family C-type lectins, exhibit distinct ligand specificities, effects on structure, host defense functions despite extensive structural homology. binds to dipalmitoylphosphatidylcholine (DPPC), major lipid component, but not phosphatidylinositol (PI), whereas SP-D shows opposite preference. Additionally, recognize widely divergent pathogen-associated molecular patterns....
Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV are largely resistant lectins, likely contributing increased spread worse outcomes. this paper, we evaluated inhibition by mannose-binding human, bacterial, fungal origin understand possibly increase activity IAV. modified version human surfactant protein D (SP-D) neck carbohydrate recognition domain (NCRD) with...