A5069180601- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Congenital heart defects research
- Renal and related cancers
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Tracheal and airway disorders
- Hippo pathway signaling and YAP/TAZ
- Proteoglycans and glycosaminoglycans research
- Neuroscience of respiration and sleep
- Tissue Engineering and Regenerative Medicine
- Developmental Biology and Gene Regulation
- Respiratory Support and Mechanisms
- Congenital Anomalies and Fetal Surgery
- Pulmonary Hypertension Research and Treatments
- Inhalation and Respiratory Drug Delivery
- Wnt/β-catenin signaling in development and cancer
- Glycosylation and Glycoproteins Research
- Retinoids in leukemia and cellular processes
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Genetic and Kidney Cyst Diseases
- Infant Nutrition and Health
- Pediatric health and respiratory diseases
- Cancer-related gene regulation
Columbia University Irving Medical Center
2016-2025
Columbia University
2014-2023
Pulmonary and Allergy Associates
2021
Boston University
2007-2017
Washington Center
2016
University of Washington
2016
American Thoracic Society
2016
University of Vermont
2016
Cystic Fibrosis Foundation
2016
European Respiratory Society
2016
We assessed the capacity of plastic-adherent cultured bone marrow cells to serve as precursors differentiated parenchymal lung. By intravenously delivering lacZ-labeled into wild-type recipient mice after bleomycin-induced lung injury, we detected marrow-derived engrafted in parenchyma with morphological and molecular phenotype type I pneumocytes alveolar epithelium. At no time cell injection, did detect any engraftment II pneumocytes. In addition, found that fresh aspirates can express...
Section:ChooseTop of pageAbstract <<MATERIALS AND METHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Although there is accumulated evidence of a role for Notch in the developing lung, it still unclear how disruption signaling affects lung progenitor cell fate and differentiation events airway epithelium. To address this issue, we inactivated conditionally endoderm using Shh-Cre deleter mouse line mice carrying floxed alleles Pofut1 gene, which encodes an O-fucosyltransferase essential Notch-ligand binding. We also took same conditional approach to inactivate expression Rbpjk,...
Highlights•Yap regulates proximal-distal patterning of the developing lung•Yap specifies a transcriptional program crucial to generate airways•Yap is required render airway progenitors responsive TGF-β and induce Sox2•Yap phosphorylation key for differentiation during embryonic adult lifeSummaryHow epithelial progenitor cells integrate local signals balance expansion with organogenesis still little understood. Here, we provide evidence that Hippo pathway effector Yap regulator this process...
Fibroblast growth factor (FGF) signaling is required for normal epithelial branching in the respiratory system of several species. Recent studies have shown that FGF-10 may be a key regulator lung morphogenesis, based on its pattern expression early and ability to induce buddingin vitro.In this study we investigate whether able direct buds proper positions during development . We maintained localized high levels cultured lungs using FGF-10-soaked heparin beads. exerts powerful...
Little is known about how retinoic acid (RA) synthesis, utilization and metabolism are regulated in the embryonic lung these activities relate to pattern formation. Here we report that early bud formation subsequent branching morphogenesis characterized by distinct stages of RA signaling. At onset development signaling ubiquitously activated primary buds, as shown expression major RA-synthesizing enzyme, RALDH-2 activation a RARE-lacZ transgene. Nevertheless, further airway appears require...
Cellular activities that lead to organogenesis are mediated by epithelial-mesenchymal interactions, which ultimately result from local activation of complex gene networks. Fibroblast growth factor (FGF) signaling is an essential component the regulatory network present in embryonic lung, controlling proliferation, differentiation and pattern formation . However, little known about how FGFs interact with other molecules these processes. By using cell organ culture systems, we provide evidence...
The purpose of the workshop was to identify still obscure or novel cellular components lung, determine cell function in lung development and health that impacts on disease, decide promising avenues for future research extract phenotype these cells. Since robust technologies are now available identify, sort, purify, culture, cells, progress is within sight unravel origins functional capabilities cells developmental stages disease. Workshop's agenda first discuss lung's embryologic...
Establishment of anteroposterior (AP) polarity is one the earliest decisions in cardiogenesis and plays an important role coupling between heart blood vessels. Recent research implicated retinoic acid (RA) communication AP to heart. We utilized embryo culture, situ hybridization, morphometry, fate mapping treatment with RA pan-antagonist BMS493 investigate relationship cardiac precursors signalling. describe two phases signalling by RA, reflected RALDH2 expression. The first phase (HH4-7)...
Reduced expression of miR-129 has been reported in multiple tumor cell lines and primary tumors including medulloblastoma, undifferentiated gastric cancers, lung adenocarcinoma, endometrial cancer colorectal carcinoma. There is also recent evidence an antiproliferative activity lines. Still, little known about how regulates proliferation. Here we found that lentiviral-mediated over-expression mouse epithelial cells (E10 cells) results significant G1 phase arrest eventually leads to death....
Disruption of retinoic acid (RA) signaling during early development results in severe respiratory tract abnormalities, including lung agenesis. Previous studies suggest that this might result from failure to selectively induce fibroblast growth factor 10 (Fgf10) the prospective region foregut. Little is known about RA-dependent pathways present foregut may be crucial for formation. By performing global gene expression analysis RA-deficient foreguts a genetic [retinaldehyde dehydrogenase 2...
Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor expand transition to differentiation form pseudostratified epithelium in developing adult lung. Here, we show by genetic pharmacological approaches endogenous activation Notch3 signaling selectively controls pool undifferentiated upper airways available differentiation. This mechanism depends...
Clara cells of mammalian airways have multiple functions and are morphologically heterogeneous. Although Notch signaling is essential for the development these cells, it unclear how influences cell specification if diversity established among precursors. Here we identify expression secretoglobin Scgb3a2 activation as early events in a program secretory fate determination developing murine airways. We show that vivo Notch-dependent at stages ectopically induced by constitutive Notch1...
The developmental abnormalities associated with disruption of signaling by retinoic acid (RA), the biologically active form vitamin A, have been known for decades from studies in animal models and humans. These include defects respiratory system, such as lung hypoplasia agenesis. However, molecular events controlled RA that lead to formation primordium primitive foregut remain unclear. Here, we present evidence endogenous acts a major regulatory signal integrating Wnt Tgfbeta pathways...
Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known regulate airway branch development. We demonstrate that in vivo central present 26.5% of the general population, unchanged over 10 y, and exhibit strong familial aggregation. The most common variant two cohorts (n = 5,054), greater bifurcation density, emphysema throughout lung. second among smokers, narrower...
Significance Formation of the gas-exchange region lung occurs largely postnatally through a process called alveologenesis. Alveolar abnormalities are hallmark neonatal and adult chronic diseases. Here we report that disruption Notch signaling in mice, particularly by Notch2, results abnormal enlargement alveolar spaces reminiscent seen We provide evidence is crucial to mediate cross-talk between different cell layers, including signals such as PDGF for formation alveoli maintenance integrity...
Highlights•U-CCs are located in the intrapulmonary airways and enriched neuroepithelial bodies•These cells contribute toward airway maintenance long-term post-injury repair•U-CCs have a higher propensity to generate ciliated than non-U-CCs•They also alveolar repair after bleomycin injurySummaryThere is evidence that certain club (CCs) murine associated with bodies (NEBs) terminal bronchioles resistant xenobiotic naphthalene (Nap) repopulate Nap injury. The identity significance of these...
Studies of collagen and elastin in pulmonary emphysema have been controversial. The problems involve methodologic differences; often whole lungs sampled the types not classified. Quantification is important since increase supports inflammatory-repair hypothesis emphysema, which has recently revived. On other hand, loss protease-antiprotease hypothesis. Accordingly, we measured (hydroxy-proline) (desmosine) 147 small samples human removed for cancer. amount type were also assessed...