A5062224123- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- Tracheal and airway disorders
- Tissue Engineering and Regenerative Medicine
- Neuroscience of respiration and sleep
- Renal and related cancers
- Pharmacogenetics and Drug Metabolism
- Cancer Cells and Metastasis
- Infant Nutrition and Health
- Respiratory Support and Mechanisms
- Respiratory viral infections research
- Fibroblast Growth Factor Research
- Single-cell and spatial transcriptomics
- Pregnancy and preeclampsia studies
- Cystic Fibrosis Research Advances
- Hormonal and reproductive studies
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Hippo pathway signaling and YAP/TAZ
- Asthma and respiratory diseases
- Extracellular vesicles in disease
- RNA modifications and cancer
Cedars-Sinai Medical Center
2016-2025
Lung Institute
1975-2024
Institute for Women's Policy Research
2020-2024
Regenerative Medicine Institute
2015-2022
Pulmonary and Critical Care Associates
2022
Duke University
2008-2021
California Institute for Regenerative Medicine
2021
University College London
2021
Institute of Biomedical Science
2019
Duke Medical Center
2008-2016
Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and 1 epithelial cells (AEC2s AEC1s), capillaries, various resident mesenchymal cells. Here, we use a combination vivo clonal lineage analysis, different injury/repair systems, vitro culture purified cell populations to obtain new information about contribution AEC2s alveolar maintenance repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) self renew...
Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic that enhances the spreading and stability of surfactant phospholipids in alveolus. To further assess role SP-B lung function, gene was disrupted by homologous recombination murine mouse embryonic stem cells. Mice with a single mutated allele (+/-) were unaffected, whereas homozygous -/- offspring died respiratory failure immediately after birth. Lungs mice developed normally but remained atelectatic spite postnatal efforts. mRNA...
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...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Fibroblast heterogeneity has long been recognized in mouse and human lungs, homeostasis, disease states. However, there is no common consensus on fibroblast subtypes, lineages, biological properties, signaling, plasticity, which severely hampers our understanding of the mechanisms fibrosis. To comprehensively classify populations lung using an unbiased approach, single-cell RNA sequencing was performed with mesenchymal preparations from either uninjured or bleomycin-treated lungs....
Remodeling of the conducting airway epithelium is a common finding in chronically injured lung and has been associated with increased risk for developing cancer. Pulmonary neuroendocrine cells clusters these termed neuroepithelial bodies (NEBs) play central role each processes. We previously developed an adult mouse model injury repair which epithelial regeneration after naphthalene-induced Clara cell ablation occurred preferentially at branch points gave rise to nascent cells. Continued was...
The surfactant protein A (SP-A) gene was disrupted by homologous recombination in embryonic stem cells that were used to generate homozygous SP-A-deficient mice. SP-A mRNA and not detectable the lungs of SP-A(-/-) mice, perinatal survival mice altered compared with wild-type Lung morphology, proteins B-D, lung tissue, alveolar phospholipid pool sizes composition, compliance unaltered. At highest concentration tested, from produced same surface tension as (+/+) lower concentrations, minimum...
The composition of the conducting airway epithelium varies significantly along proximal to distal axis, with that tracheal exhibiting greatest complexity. A number progenitor cells have been proposed contribute maintenance this cellular diversity both in steady state and response injury. However, individual roles for each cell type are poorly defined vivo. present study was undertaken investigate hypothesis basal represent a multipotent renewal injured epithelium. To understand their...
Rationale: Idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining function. Accelerated aging, loss of epithelial progenitor cell function and/or numbers, cellular senescence are implicated in the pathogenies IPF. Objectives: We sought to investigate role alveolar type 2 (AT2) initiation progression therapeutic potential targeting senescence-related pathways senescent cells. Methods: Epithelial cells 9 control donor proximal distal...
The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size stem/progenitor behavior. Following airway injury, Yap was dynamically regulated in regenerating epithelial cells. To determine the role of Hippo lung, mammalian kinases, Mst1 Mst2, were deleted cells embryonic mature mouse lung. Mst1/2 deletion fetal lung enhanced inhibited sacculation differentiation. transcriptional inhibition activation during normal...
Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies CF. However, a full characterization expression in normal human airway epithelia missing. Objectives: To identify that contribute to and function within proximal–distal axis lung. Methods: Single-cell RNA (scRNA) sequencing (scRNA-seq) was performed on freshly isolated large small epithelial cells. scRNA situ...
Recent studies have demonstrated immunologic dysfunction in severely ill coronavirus disease 2019 (COVID-19) patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) from healthy (n = 3) and COVID-19 patients with moderate 5), acute respiratory distress syndrome (ARDS, n 6), or recovering ARDS 6). Our data reveal transcriptomic profiles indicative defective antigen presentation interferon (IFN) responsiveness monocytes...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the system can progress to a multisystemic disease with aberrant inflammatory response. Cellular senescence promotes chronic inflammation, named senescence-associated secretory phenotype (SASP). We investigated whether 2019 (COVID-19) is associated cellular and SASP.Autopsy lung tissue samples from 11 COVID-19 patients 43 age-matched non-COVID-19 controls similar comorbidities were analysed by immunohistochemistry for...
To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in vivo and explore directly its relationship reactivity, we created transgenic mice which murine cDNA for IL-4 was regulated by rat Clara cell 10 protein promoter. Expression detected only lung not thymus, heart, liver, spleen, kidney, or uterus. The expression elicited hypertrophy epithelial cells trachea, bronchi, bronchioles. Hypertrophy is due, at least part, accumulation mucus glycoprotein. Histologic...
Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype mouse airway mucous cells. In naive mice, ciliated (approximately 40%) nonciliated 60%) epithelial cells line airways, > 95% are Clara that contain cell secretory protein (CCSP). Mucous comprise < 5% After sensitization single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive numbers increase dramatically, appearing 6 h after...