A5014703407- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Pediatric health and respiratory diseases
- Infant Nutrition and Health
- IL-33, ST2, and ILC Pathways
- Gut microbiota and health
- Immune Response and Inflammation
- Preterm Birth and Chorioamnionitis
- Antimicrobial Resistance in Staphylococcus
- Asthma and respiratory diseases
- Neonatal and Maternal Infections
- Reproductive System and Pregnancy
- Diabetes and associated disorders
- Systemic Lupus Erythematosus Research
- Glycosylation and Glycoproteins Research
- Airway Management and Intubation Techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pulmonary Hypertension Research and Treatments
- Medical Imaging and Pathology Studies
- NF-κB Signaling Pathways
- Polysaccharides and Plant Cell Walls
- Blood disorders and treatments
- Tracheal and airway disorders
Cincinnati Children's Hospital Medical Center
2005-2024
University of Cincinnati Medical Center
2005-2024
University of Cincinnati
2007-2024
United States University
2023
Children's Hospital & Medical Center
2020-2022
Children’s Institute
2019
University of Pennsylvania
2013-2014
Children's Hospital of Philadelphia
2013-2014
Georgia Institute of Technology
2014
Emory University
2014
CRISPR/Cas9 systems are a versatile tool for genome editing due to the highly efficient targeting of DNA sequences complementary their RNA guide strands. However, it has been shown that RNA-guided Cas9 nuclease cleaves genomic containing mismatches strand. A better understanding specificity is needed minimize off-target cleavage in large mammalian genomes. Here we show sites could be cleaved by when contain insertions (‘DNA bulge’) or deletions (‘RNA compared strand, and nickases used paired...
The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth. To identify the heterogeneity pulmonary cell types dynamic in gene expression mediating respiration, here we perform single RNA analyses mouse lung on postnatal day 1. Using an iterative type identification strategy unbiasedly murine types. We distinct populations epithelial, endothelial, mesenchymal, immune cells, each containing subpopulations....
Postnatal colonization by intestinal commensal bacteria directs migration of innate lymphoid cells to the lungs and promotes resistance newborn mice pneumonia.
The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing genetic lineage tracing have revealed novel cell types enriched functional properties of existing lung. time has come to take a new census. Initiated by members the NHLBI-funded LungMAP Consortium aided experts biology community, we synthesized current data into comprehensive practical cellular census Identities normal are captured...
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder the lung defined by constellation characteristic histopathological features. Nonpulmonary anomalies involving organs gastrointestinal, cardiovascular, genitourinary systems have been identified in approximately 80% patients ACD/MPV. We collected DNA pathological samples from more than 90 infants ACD/MPV their family members. Since publication our initial report four point...
The impact of bacterial genetic characteristics on the outcome patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between genotype and clinical using isolates collected as part an international phase 2 trial (FAST II) evaluating telavancin for treatment complicated skin structure (cSSSI). Ninety S. from microbiologically evaluable cSSSI enrolled in FAST II 11 sites United States (56 isolates, or 62%) 7 South Africa (34 38%) were...
Chronic obstructive pulmonary disease is marked by alveolar enlargement and excess production of airway mucus. Acrolein, a component cigarette smoke, increases mucin 5AC (MUC5AC), prevalent in NCI-H292 cells transcriptional activation, but the signal transduction pathways involved acrolein-induced MUC5AC expression are unknown. Acrolein depleted cellular glutathione at doses 10 muM or greater, higher than those sufficient (0.03 muM) to increase mRNA, suggesting that was independent oxidative...
NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role the response Staphylococcus aureus infection unknown. NOD2-deficient (Nod2(-/-)) mice and wild-type (WT) littermate controls were injected intraperitoneally with S. suspension (10(7) bacteria/g body weight), their survival was monitored. Cultured bone marrow-derived neutrophils harvested from Nod2(-/-) WT tested for cytokine production...
Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially the small airways. Acrolein, constituent of cigarette smoke and an endogenous mediator oxidative stress, increases airway 5, subtypes A C (MUC5AC) production; however, mechanism remains unclear. In this study, mMUC5AC transcripts protein were associated lung matrix metalloproteinase 9 (mMMP9) transcripts, protein,...
We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an between SLE or ITGAM-ITGAX region. The primary objectives this study are to assess whether single multiple causal variants from same any nearby gene(s) involved confirm robust across nine...
Objective Late onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from gut, distortions gut microbial community increases subsequent risk of LOS. Study Design examined prospectively collected stool samples infants with an equal number age-matched controls at two sites (Cincinnati, OH Birmingham, AL), by sequencing bacterial 16S rDNA. confirmed our findings a subset whole genome shotgun sequencing,...
Although modern clinical practices such as cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum alters intestinal microbiota causes dysbiosis. Infants exposed to an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how the gut sculpt pulmonary immune responses, promoting recovery resolution infection in newborn rhesus macaques. Early-life antibiotic exposure interrupted maturation commensal...
Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared C57BL/6J, the specific genes responsible for this differential phenotype unknown. Using chromosome substitution strains (CSS), we found loci on chromosomes 8, 11, and 18 influence susceptibility S. in mice. We then used two candidate gene selection strategies identify these three associated with susceptibility, targeted identified by both strategies. First, whole genome...
Induced mainly by cigarette smoking, chronic obstructive pulmonary disease (COPD) is a global public health problem characterized progressive difficulty in breathing and increased mucin production. Previously, we reported that acrolein levels found COPD sputum could activate matrix metalloproteinase-9 (MMP9).To determine whether increases expression activity of MMP14, critical membrane-bound endopeptidase can initial MMP-activation cascade.MMP14 adduct formation were measured following...
We have previously demonstrated that the circadian clock regulates host response to influenza A virus (IAV) infection, conferring a time-of-day-specific protection; infection at dawn resulted in threefold increase survival and reduced immunopathology compared dusk. While IL–10 is well-known for its immunoregulatory function, role IAV remains unclear, with studies reporting both protective detrimental effects. Given diurnal rhythmicity of receptor (Il10ra) expression lung, we investigated...
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Using A/J mice, which are susceptible to Staphylococcus aureus, we sought identify genetic determinants of susceptibility S. and evaluate their function with regard aureus infection. One QTL region on chromosome 11 containing 422 genes was found be significantly associated Of these genes, whole genome transcription profiling identified five (Dcaf7, Dusp3, Fam134c, Psme3, Slc4a1) that were differentially expressed in a) –infected (A/J) vs. resistant (C57BL/6J) mice b) humans blood stream...
Perinatal inflammatory stress is associated with early life morbidity and lifelong consequences for pulmonary health. Chorioamnionitis, an condition affecting the placenta fluid surrounding developing fetus, affects 25 to 40% of preterm births. Severe chorioamnionitis birth significantly increased risk disease secondary infections in childhood, suggesting that fetal inflammation may markedly alter development lung. Here, we used intra-amniotic lipopolysaccharide (LPS) challenge induce...