Christine E. Bear
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View article: A technique for evaluating calcium flux in primary airway tissue at single cell resolution
A technique for evaluating calcium flux in primary airway tissue at single cell resolution Open
Calcium signaling is critical in a multitude of biological processes, reinforcing the need to develop methods to study calcium flux in primary tissue. The study of live calcium mobilization into the cytosol is commonly studied by intracell…
View article: An Update on Single-Cell RNA Sequencing in Illuminating Disease Mechanisms of Cutaneous T-Cell Lymphoma
An Update on Single-Cell RNA Sequencing in Illuminating Disease Mechanisms of Cutaneous T-Cell Lymphoma Open
Cutaneous T-cell Lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas that currently have an incompletely understood pathophysiology and several challenges in both diagnosis and management. Single-cell RNA sequencing (scRNA…
View article: Nasal cells as a bronchial cell surrogate for pre-clinical assessment of drug response in cystic fibrosis
Nasal cells as a bronchial cell surrogate for pre-clinical assessment of drug response in cystic fibrosis Open
Patient-derived airway cell cultures are used in personalized medicine strategies for people with cystic fibrosis (pwCF) to predict potential clinical response to cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs. …
View article: Case Study of an Atypical Presentation of a Large Undiagnosed Empyema in the Setting of Hyperglycemia
Case Study of an Atypical Presentation of a Large Undiagnosed Empyema in the Setting of Hyperglycemia Open
A 58-year-old man with a history of type 2 diabetes mellitus was hospitalized for hyperglycemia. During a review of systems, the patient reported additional symptoms of mild, right-sided pleuritic chest pain. Further investigation revealed…
View article: Impact of Early Procedural Exposure on Pre-clinical Medical Students’ Confidence
Impact of Early Procedural Exposure on Pre-clinical Medical Students’ Confidence Open
Procedural exposure and training early in medical school can promote student confidence and success during clinical clerkships.
View article: Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs
Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs Open
Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rec…
View article: Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells
Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells Open
Background Cystic Fibrosis causing mutations in the gene CFTR , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-o…
View article: Benchmarking organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs
Benchmarking organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs Open
Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rec…
View article: Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells
Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells Open
Background Cystic Fibrosis causing mutations in the gene CFTR , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-o…
View article: Collagen Tubular Airway‐on‐Chip for Extended Epithelial Culture and Investigation of Ventilation Dynamics
Collagen Tubular Airway‐on‐Chip for Extended Epithelial Culture and Investigation of Ventilation Dynamics Open
The lower respiratory tract is a hierarchical network of compliant tubular structures that are made from extracellular matrix proteins with a wall lined by an epithelium. While microfluidic airway‐on‐a‐chip models incorporate the effects o…
View article: Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity
Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity Open
While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease s…
View article: Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity
Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity Open
While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease s…
View article: Collagen Tubular Airway-on-Chip for Extended Epithelial Culture and Investigation of Ventilation Dynamics
Collagen Tubular Airway-on-Chip for Extended Epithelial Culture and Investigation of Ventilation Dynamics Open
The lower respiratory tract is a hierarchical network of compliant tubular structures that are made from extracellular matrix proteins with a wall lined by an epithelium. While microfluidic airway-on-a-chip models incorporate the effects o…
View article: A Cell-Based Optimised Approach for Rapid and Efficient Gene Editing of Human Pluripotent Stem Cells
A Cell-Based Optimised Approach for Rapid and Efficient Gene Editing of Human Pluripotent Stem Cells Open
Introducing or correcting disease-causing mutations through genome editing in human pluripotent stem cells (hPSCs) followed by tissue-specific differentiation provide sustainable models of multiorgan diseases, such as cystic fibrosis (CF).…
View article: Correlation of Electrophysiological and Fluorescence-Based Measurements of Modulator Efficacy in Nasal Epithelial Cultures Derived from People with Cystic Fibrosis
Correlation of Electrophysiological and Fluorescence-Based Measurements of Modulator Efficacy in Nasal Epithelial Cultures Derived from People with Cystic Fibrosis Open
It has been suggested that in vitro studies of the rescue effect of CFTR modulator drugs in nasal epithelial cultures derived from people with cystic fibrosis have the potential to predict clinical responses to the same drugs. Hence, there…
View article: Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis
Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis Open
Highly effective drugs modulating the defective protein encoded by the CFTR gene have revolutionized cystic fibrosis (CF) therapy. Preclinical drug-testing on human nasal epithelial (HNE) cell cultures and 3-dimensional human intestinal or…
View article: A Fluorescence-based Assay of Membrane Potential for High-throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines
A Fluorescence-based Assay of Membrane Potential for High-throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines Open
Fluorescence-based studies are suitable for high-throughput plate reader assays of cells in culture. They have been commonly employed for drug discovery campaigns targeting recombinant ion channel proteins overexpressed in cells such as HE…
View article: Viscoelastic Notch Signaling Hydrogel Induces Liver Bile Duct Organoid Growth and Morphogenesis
Viscoelastic Notch Signaling Hydrogel Induces Liver Bile Duct Organoid Growth and Morphogenesis Open
Cholangiocyte organoids can be used to model liver biliary disease; however, both a defined matrix in which to emulate cholangiocyte self-assembly and the mechano-transduction pathways involved therein remain elusive. We designed a series …
View article: A protocol for identifying the binding sites of small molecules on the cystic fibrosis transmembrane conductance regulator (CFTR) protein
A protocol for identifying the binding sites of small molecules on the cystic fibrosis transmembrane conductance regulator (CFTR) protein Open
We describe a protocol to identify the binding site(s) for a drug called ivacaftor that potentiates the CFTR chloride channel. We use photoaffinity probes-based on the structure of ivacaftor-to covalently modify the CFTR protein at the reg…
View article: CFTR interactome mapping using the mammalian membrane two‐hybrid high‐throughput screening system
CFTR interactome mapping using the mammalian membrane two‐hybrid high‐throughput screening system Open
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the …
View article: Stage‐Specific Generation of Human Pluripotent Stem Cell Derived Lung Models to Measure CFTR Function
Stage‐Specific Generation of Human Pluripotent Stem Cell Derived Lung Models to Measure CFTR Function Open
Human embryonic stem cells (ES) and induced pluripotent stem cells (iPSC) are powerful tools that have the potential to generate in vitro human lung epithelial cells. However, challenges in efficiency and reproducibility remain in utilizin…
View article: Antisense oligonucleotide splicing modulation as a novel Cystic Fibrosis therapeutic approach for the W1282X nonsense mutation
Antisense oligonucleotide splicing modulation as a novel Cystic Fibrosis therapeutic approach for the W1282X nonsense mutation Open
The highly efficient exon 23 skipping induced by free uptake of the lead ASO and the resulting levels of mature CFTR protein exhibiting channel function in the presence of modulators, demonstrate the ASO therapeutic potential benefit for C…
View article: High-Throughput Functional Analysis of CFTR and Other Apically Localized Proteins in iPSC-Derived Human Intestinal Organoids
High-Throughput Functional Analysis of CFTR and Other Apically Localized Proteins in iPSC-Derived Human Intestinal Organoids Open
Induced Pluripotent Stem Cells (iPSCs) can be differentiated into epithelial organoids that recapitulate the relevant context for CFTR and enable testing of therapies targeting Cystic Fibrosis (CF)-causing mutant proteins. However, to date…