A5001813162- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Neuroscience of respiration and sleep
- Respiratory Support and Mechanisms
- Inhalation and Respiratory Drug Delivery
- Renal and related cancers
- Epigenetics and DNA Methylation
- Infant Nutrition and Health
- Immune Response and Inflammation
- Congenital heart defects research
- Fibroblast Growth Factor Research
- Cystic Fibrosis Research Advances
- Respiratory viral infections research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Asthma and respiratory diseases
- Cancer-related gene regulation
- RNA modifications and cancer
- Virus-based gene therapy research
- Pediatric health and respiratory diseases
- FOXO transcription factor regulation
- Single-cell and spatial transcriptomics
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Kruppel-like factors research
- Medical Imaging and Pathology Studies
- Pulmonary Hypertension Research and Treatments
Cincinnati Children's Hospital Medical Center
2016-2025
Cincinnati Sportsmedicine and Orthopaedic Center
2025
University of Cincinnati
2015-2024
University of Cincinnati Medical Center
2010-2024
Perinatal Institute
2011-2023
Pulmonary Associates
2001-2021
The University of Texas Health Science Center at San Antonio
1995-2020
Children's Hospital of Los Angeles
2020
Boston Medical Center
2020
Boston University
2020
Interstitial lung diseases are a heterogeneous group of disorders that poorly understood at molecular level.1,2 The cause is often unknown, and the histologic diagnoses used in adults may represent different disease processes children.3–5 For example, cases desquamative interstitial pneumonitis reported infants more severe refractory to treatment than those adults.6,7 Many these probably chronic infancy.8,9 lungs patients with infancy characterized by thickening mesenchymal cells, rather an...
The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated mice, carrying a null allele the GM-CSF gene, that were generated by gene targeting techniques embryonic stem cells. Although steady-state hematopoiesis unimpaired homozygous mutant animals, all animals developed progressive accumulation surfactant lipids and proteins alveolar space, defining characteristic idiopathic human disorder pulmonary proteinosis. Extensive lymphoid hyperplasia...
Pulmonary surfactant forms a lipid-rich monolayer that coats the airways of lung and is essential for proper inflation function lung. Surfactant produced by alveolar type II cells, stored intracellularly in organelles known as lamellar bodies, secreted exocytosis. The gene ATP-binding cassette transporter A3 (ABCA3) expressed protein localized to suggesting it has an important role metabolism.We sequenced each coding exons ABCA3 blood DNA from 21 racially ethnically diverse infants with...
Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought determine if endogenous surfactant altered in ARDS. Bronchoalveolar lavage was performed patients at-risk develop ARDS (AR, n = 20), with (A, 66) normal subjects (N, 29). The crude pellet analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, minimum surface tension (STmin). PL decreased both AR A (3.48 +/- 0.61 2.47 0.40 mumol/ml,...
We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In previous study, we showed that SPB specifically activated expression linked reporter continuous H441 cell line and nuclear proteins protected region this from bp -111 -73. further show is complex binding site for thyroid transcription factor 1 (TTF-1) hepatocyte 3 (HNF-3). Whereas TTF-1 bound two...
To establish the timing of lineage restriction among endodermal derivatives, we developed a method to label permanently subsets lung precursor cells at defined times during development by using Cre recombinase activate floxed alkaline phosphatase or green fluorescent protein genes under control doxycycline-dependent surfactant C promoter. Extensive complete labeling peripheral lung, thyroid, and thymic epithelia, but not trachea, bronchi, gastrointestinal tract occurred when mice were...
Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis normal human cells defined gene expression patterns with highly differentiated type 2 (AT2) cells, indicated enrichment RNAs critical for surfactant...
The goal of this study was to determine the changes that occur in surfactant-associated proteins bronchoalveolar lavage fluid (BAL) and serum patients at risk for ARDS during course ARDS. We found concentrations SP-A SP-B were low BAL before onset clinically defined lung injury, whereas concentration SP-D normal. In with established ARDS, entire 14-d observation period, but median remained normal range. Immunoreactive not increased both after a maximum on Day 3 elevated as long 14 d....
The production of the inflammatory cytokine interleukin (IL)-1 is increased in lungs patients with chronic obstructive pulmonary disease (COPD) or asthma. To characterize vivo actions IL-1 lung, transgenic mice were generated which human IL-1beta was expressed lung epithelium a doxycycline-inducible system controlled by rat Clara cell secretory protein (CCSP) promoter. Induction expression adult caused inflammation characterized neutrophil and macrophage infiltrates. distal airspace...
Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in lungs SP-D (−/−) mice. Although lung morphology was unperturbed during first 2 weeks life, airspace enlargement observed by 3 progressed with advancing age. Inflammation consisted hypertrophic alveolar macrophages peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated increased activity matrix metalloproteinases, MMP2 MMP9, immunostaining for MMP9...
Various acute and chronic inflammatory stimuli increase the number activity of pulmonary mucus-producing goblet cells, cell hyperplasia excess mucus production are central to pathogenesis diseases. However, little is known about transcriptional programs that regulate differentiation. Here, we show SAM-pointed domain–containing Ets-like factor (SPDEF) controls a program critical for differentiation in mice. Initial cell-lineage–tracing analysis identified nonciliated secretory epithelial as...
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with...
A major challenge in developmental biology is to understand the genetic and cellular processes/programs driving organ formation differentiation of diverse cell types that comprise embryo. While recent studies using single transcriptome analysis illustrate power measure heterogeneity complex biological systems, processing large amounts RNA-seq data from heterogeneous populations creates need for readily accessible tools single-cell (scRNA-seq) profiles. The present study presents a generally...