A5036335582- Neonatal Respiratory Health Research
- Genetic and Kidney Cyst Diseases
- Cystic Fibrosis Research Advances
- Protist diversity and phylogeny
- Respiratory viral infections research
- Renal and related cancers
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Epigenetics and DNA Methylation
- Tracheal and airway disorders
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Microtubule and mitosis dynamics
- Inhalation and Respiratory Drug Delivery
- Transplantation: Methods and Outcomes
- RNA Interference and Gene Delivery
- SARS-CoV-2 and COVID-19 Research
- Medical Imaging and Pathology Studies
- Autophagy in Disease and Therapy
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
- Influenza Virus Research Studies
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Cerebrospinal fluid and hydrocephalus
Washington University in St. Louis
2016-2025
Mallinckrodt (United States)
1995-2023
Pulmonary and Critical Care Associates
2013-2021
MetroHealth Medical Center
2015
Case Western Reserve University
2015
University of Southern California
2013
University of California, Berkeley
2008-2009
Institute of Bioorganic Chemistry
2009
University of Ottawa
2009
Pulmonary Associates
1978-2007
Highly regulated programs for airway epithelial cell proliferation and differentiation during development repair are often disrupted in disease. These processes have been studied mouse models; however, it is difficult to isolate identify cell-specific responses vivo. To investigate these vitro, we characterized a model primary culture of tracheal cells. Small numbers cells seeded at low density (7.5 × 10 4 cells/cm 2 ) rapidly proliferated became polarized. Subsequently, supplemented media...
Recent human infections caused by the highly pathogenic avian influenza virus H5N1 strains emphasize an urgent need for assessment of factors that allow viral transmission, replication, and intra-airway spread. Important determinants infection are epithelial cell receptors identified as glycans terminated alpha2,3-linked sialic acid (SA) preferentially bind alpha2,6-linked SA strains. The mouse is often used a model study viruses, including recent strains; however, selectivity specific...
Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least part, infection. Analysis of parainfluenza virus infection mice revealed an unexpected role for innate cells IL-13–dependent chronic disease, but the upstream driver axis this model humans with similar was undefined. We demonstrate here levels IL-33 selectively increased postviral very severe pulmonary (COPD). In mouse model, IL-33/IL-33 receptor...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive infection despite complete absence angiotensin-converting enzyme (ACE2) expression. Remarkably, requires the E484D S variant; viruses expressing wild-type are not infectious. Anti-S monoclonal antibodies...
Abstract Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion protocols require prior treatment reactive anchoring chemicals to link specific labels biomolecule classes the gel. We describe strategy called Magnify, which uses mechanically sturdy gel that retains nucleic acids, proteins lipids without need for separate step. Magnify...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Neuronal specification occurs at the periventricular surface of embryonic central nervous system. During early postnatal periods, radial glial cells in various ventricular zones brain differentiate into ependymal and astrocytes. However, mechanisms that drive this time- cell-specific differentiation remain largely unknown. Here, we show expression forkhead transcription factor FoxJ1 mice is required for a small subset FoxJ1+ astrocytes lateral ventricles, where these form neural stem cell...
NIMELSTEIN, STEPHEN H. M.D.; BRODY, STEVEN MCSHANE, DENNIS HOLMAN, HALSTED R. M.D. Author Information
Programs that direct cellular differentiation are dependent on the strict temporal expression of regulatory factors can be provided by Rho GTPases. Ciliogenesis is a complex sequence events involving generation and docking basal bodies at apical membrane, followed ciliary axoneme generation. Although cilia proteome has been assembled, programs ciliated cell not well established, particularly in mammalian systems. Using mouse primary culture airway epithelial cells, we identified critical...
Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated are unknown. Cell ultrastructure analysis indicates activates multistage program involving synthesis cilia precursor proteins and assembly macromolecular complexes. Foxj1 is f-box transcription factor expressed in cells shown be formation by gene deletion mouse model. To identify specific role foxj1 directing the phenotype, we evaluated capacity induce ciliogenesis direct assembly. In primary culture...
Restenosis, a process characterized in part by excessive smooth muscle cell (SMC) proliferation areas of vascular injury, occurs up to 50% patients undergoing balloon angioplasty. In an effort develop treatment strategy for restenosis, we constructed replication-deficient recombinant adenovirus (AdMLP.HSTK) containing the herpes simplex virus thymidine kinase gene (HSV tk). This viral product phosphorylates prodrug ganciclovir form nucleoside analog that inhibits DNA synthesis. Cultured...
Motile cilia are essential components of the mucociliary escalator and central to respiratory-tract host defenses. Abnormalities in these evolutionarily conserved organelles cause primary ciliary dyskinesia (PCD). Despite recent strides characterizing ciliome sensory ciliopathies through exploration phenotype-genotype associations model organisms, genetic bases most cases PCD remain elusive. We identified nine related subjects with from geographically dispersed Amish communities performed...
Cilia are traditionally classified as motile or primary. Motile cilia restricted to specific populations of well-differentiated epithelial cells, including those in the airway, brain ventricles, and oviducts. Primary nonmotile, solitary structures that present many cell types, often have sensory functions such retina renal tubules. were also implicated regulation fundamental processes development. Rare depictions primary embryonic airways led us hypothesize airway cells temporally related...
Cytokine modulation of autophagy is increasingly recognized in disease pathogenesis, and current concepts suggest that type 1 cytokines activate autophagy, whereas 2 are inhibitory. However, this paradigm derives primarily from studies immune cells poorly characterized tissue cells, including sentinel epithelial regulate the response. In particular, cytokine IL13 (interleukin 13) drives formation airway goblet secrete excess mucus as a characteristic feature disease, but whether process...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Background Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by impaired function, leading to chronic sinopulmonary disease. The causes of PCD are still evolving, while the diagnosis often dependent on finding ultrastructural abnormality and immotile cilia. Here we report novel gene associated with but without abnormalities evident transmission electron microscopy, dyskinetic cilia beating. Methods Genetic linkage analysis was performed in family subject. Gene expression...
Paradigm shifting studies have revealed that the heart contains functionally diverse populations of macrophages derived from distinct embryonic and adult hematopoietic progenitors. Under steady-state conditions, is largely populated by CCR2- (C-C chemokine receptor type 2) descent. After tissue injury, a dramatic shift in macrophage composition occurs whereby CCR2+ monocytes are recruited to differentiate into inflammatory contribute failure progression. Currently, there no techniques...
Despite recent progress in defining the ciliome, genetic basis for many cases of primary ciliary dyskinesia (PCD) remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 one candidate was conserved organisms motile cilia. Sequencing novel mutation LRRC6...
Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of activity or treatment responses. Monocyte and interstitial macrophages that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF central to fibrosis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines primary airway cells grown at an air-liquid interface gain deeper understanding the translationally regulated events response virus replication. We found that SARS-CoV-2 mRNAs dominate cellular pool but are not more efficiently translated than mRNAs. utilized highly efficient...