The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Deborah R Gill - One of the best experts on this subject based on the ideXlab platform.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2021Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells, which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days after air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus glycoproteins F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium, especially for the development of advanced therapy medicinal products targeting monogenic disorders.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2020Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Abstract Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder which leads to loss of life in infants due to alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days post air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium especially for the development of advanced therapy medicinal products targeting monogenic disorders.
Altar M Munis - One of the best experts on this subject based on the ideXlab platform.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2021Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells, which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days after air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus glycoproteins F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium, especially for the development of advanced therapy medicinal products targeting monogenic disorders.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2020Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Abstract Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder which leads to loss of life in infants due to alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days post air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium especially for the development of advanced therapy medicinal products targeting monogenic disorders.
Samuel W Hulbert - One of the best experts on this subject based on the ideXlab platform.
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altered mglur5 homer scaffolds and corticostriatal connectivity in a shank3 complete Knockout Model of autism
Nature Communications, 2016Co-Authors: Xiaoming Wang, Alexandra L Bey, Brittany M Katz, Alexandra Badea, Nam Soo Kim, Lisa K David, Lara J Duffney, Sunil Kumar, Stephen D Mague, Samuel W HulbertAbstract:SHANK3 mutations have been linked to autism spectrum disorders, although the underlying mechanisms remain unclear. Here, the authors generate a complete Knockout Shank3 mouse Model, identifying ASD-like behaviours associated with impaired mGluR5-Homer scaffolding and abnormal brain connectivity.
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altered mglur5 homer scaffolds and corticostriatal connectivity in a shank3 complete Knockout Model of autism
Nature Communications, 2016Co-Authors: Xiaoming Wang, Alexandra L Bey, Brittany M Katz, Alexandra Badea, Nam Soo Kim, Lisa K David, Lara J Duffney, Sunil Kumar, Stephen D Mague, Samuel W HulbertAbstract:Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete Knockout mouse Model of the autism-associated Shank3 gene, with a deletion of exons 4–22 (Δe4–22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4–22−/− mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs. SHANK3 mutations have been linked to autism spectrum disorders, although the underlying mechanisms remain unclear. Here, the authors generate a complete Knockout Shank3 mouse Model, identifying ASD-like behaviours associated with impaired mGluR5-Homer scaffolding and abnormal brain connectivity.
Stephen C Hyde - One of the best experts on this subject based on the ideXlab platform.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2021Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells, which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days after air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus glycoproteins F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium, especially for the development of advanced therapy medicinal products targeting monogenic disorders.
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a human surfactant b deficiency air liquid interface cell culture Model suitable for gene therapy applications
Molecular therapy. Methods & clinical development, 2020Co-Authors: Altar M Munis, Stephen C Hyde, Deborah R GillAbstract:Abstract Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder which leads to loss of life in infants due to alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized and physiologically relevant in vitro Models of human lung parenchyma. Here, we describe a new human surfactant air-liquid interface (SALI) culture Model based on H441 cells which successfully recapitulates the key characteristics of human alveolar cells in primary culture as evidenced by RNA and protein expression of alveolar cell markers. SALI cultures were able to develop stratified cellular layers with functional barrier properties that are stable for at least 28 days post air-lift. A SFTPB Knockout Model of SPB deficiency was generated via gene editing of SALI cultures. The SFTPB-edited SALI cultures lost expression of SPB completely and showed weaker functional barrier properties. We were able to correct this phenotype via delivery of a lentiviral vector pseudotyped with Sendai virus F/HN expressing SPB. We believe that SALI cultures can serve as an important in vitro research tool to study human alveolar epithelium especially for the development of advanced therapy medicinal products targeting monogenic disorders.
Xiaoming Wang - One of the best experts on this subject based on the ideXlab platform.
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altered mglur5 homer scaffolds and corticostriatal connectivity in a shank3 complete Knockout Model of autism
Nature Communications, 2016Co-Authors: Xiaoming Wang, Alexandra L Bey, Brittany M Katz, Alexandra Badea, Nam Soo Kim, Lisa K David, Lara J Duffney, Sunil Kumar, Stephen D Mague, Samuel W HulbertAbstract:SHANK3 mutations have been linked to autism spectrum disorders, although the underlying mechanisms remain unclear. Here, the authors generate a complete Knockout Shank3 mouse Model, identifying ASD-like behaviours associated with impaired mGluR5-Homer scaffolding and abnormal brain connectivity.
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altered mglur5 homer scaffolds and corticostriatal connectivity in a shank3 complete Knockout Model of autism
Nature Communications, 2016Co-Authors: Xiaoming Wang, Alexandra L Bey, Brittany M Katz, Alexandra Badea, Nam Soo Kim, Lisa K David, Lara J Duffney, Sunil Kumar, Stephen D Mague, Samuel W HulbertAbstract:Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete Knockout mouse Model of the autism-associated Shank3 gene, with a deletion of exons 4–22 (Δe4–22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4–22−/− mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs. SHANK3 mutations have been linked to autism spectrum disorders, although the underlying mechanisms remain unclear. Here, the authors generate a complete Knockout Shank3 mouse Model, identifying ASD-like behaviours associated with impaired mGluR5-Homer scaffolding and abnormal brain connectivity.
