Emmanuel Osei - Academia.edu (original) (raw)

Papers by Emmanuel Osei

Research paper thumbnail of Modeling Extracellular Matrix-Cell Interactions in Lung Repair and Chronic Disease

Cells, 2021

The lung extracellular matrix (ECM) is a complex and dynamic mixture of fibrous proteins (collage... more The lung extracellular matrix (ECM) is a complex and dynamic mixture of fibrous proteins (collagen, elastin), glycoproteins (fibronectin, laminin), glycosaminoglycans (heparin, hyaluronic acid) and proteoglycans (perlecan, versican), that are essential for normal lung development and organ health [...]

Research paper thumbnail of The Role Of Interleukin-1 In Driving Inflammation And Remodeling In The Asthmatic Emtu

American Journal of Respiratory and Critical Care Medicine, 2017

Research paper thumbnail of What Have In Vitro Co-Culture Models Taught Us about the Contribution of Epithelial-Mesenchymal Interactions to Airway Inflammation and Remodeling in Asthma?

Cells, 2020

As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental process... more As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental processes that drive cell proliferation, differentiation, and extracellular matrix (ECM) production within the lung epithelial-mesenchymal trophic unit (EMTU). In asthma, a number of the lung EMTU developmental signals have been associated with airway inflammation and remodeling, which has led to the hypothesis that aberrant activation of the asthmatic EMTU may lead to disease pathogenesis. Monoculture studies have aided in the understanding of the altered phenotype of airway epithelial and mesenchymal cells and their contribution to the pathogenesis of asthma. However, 3-dimensional (3D) co-culture models are needed to enable the study of epithelial-mesenchymal crosstalk in the setting of the in vivo environment. In this review, we summarize studies using 3D co-culture models to assess how defective epithelial-mesenchymal communication contributes to chronic airway inflammation and remodeling ...

Research paper thumbnail of Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma

Scientific Reports, 2020

In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role i... more In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to control...

Research paper thumbnail of An In-Situ Single Cell Atlas of the Terminal Bronchioles in Chronic Obstructive Pulmonary Disease by Imaging Mass Cytometry

C18. IMAGING MECHANISMS OF LUNG DISEASE, 2020

Research paper thumbnail of Super resolution measurement of collagen fibers in biological samples: Validation of a commercial solution for multiphoton microscopy

PLOS ONE, 2020

Multiphoton microscopy is a powerful, non-invasive technique to image biological specimens. One c... more Multiphoton microscopy is a powerful, non-invasive technique to image biological specimens. One current limitation of multiphoton microscopy is resolution as many of the biological molecules and structures investigated by research groups are similar in size or smaller than the diffraction limit. To date, the combination of multiphoton and super-resolution imaging has proved technically challenging for biology focused laboratories to implement. Here we validate that the commercial super-resolution Airyscan detector from ZEISS, which is based on image scanning microscopy, can be integrated under warranty with a pulsed multi-photon laser to enable multiphoton microscopy with super-resolution. We demonstrate its biological application in two different imaging modalities, second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), to measure the fibre thicknesses of collagen and elastin molecules surpassing the diffraction limit by a factor of 1.7±0.3x and 1.4±0.3x respectively, in human heart and lung tissues, and 3-dimensional in vitro models. We show that enhanced resolution and signal-to-noise of SHG using the Airyscan compared to traditional GaAs detectors allows for automated and precise measurement of collagen fibres using texture analysis in biological tissues.

Research paper thumbnail of Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD

European Respiratory Journal, 2019

Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality... more Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide. In the context of disease pathogenesis, both asthma and COPD involve chronic inflammation of the lung and are characterised by the abnormal release of inflammatory cytokines, dysregulated immune cell activity and remodelling of the airways. To date, current treatments still only manage symptoms and do not reverse the primary disease processes. In recent work, interleukin (IL)-1α and IL-1β have been suggested to play important roles in both asthma and COPD. In this review, we summarise overwhelming pre-clinical evidence for dysregulated signalling of IL-1α and IL-1β contributing to disease pathogenesis and discuss the paradox of IL-1 therapeutic studies in asthma and COPD. This is particularly important given recent completed and ongoing clinical trials with IL-1 biologics that have had varying degrees of failure and success as therapeutics for disease modification in asthma a...

Research paper thumbnail of miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD

The European respiratory journal, 2017

We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived infl... more We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial-mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreas...

Research paper thumbnail of Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD

European Respiratory Journal, 2016

Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesench... more Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-...

Research paper thumbnail of Unravelling the complexity of COPD by microRNAs: it's a small world after all

European Respiratory Journal, 2015

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the f... more Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking.In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future...

Research paper thumbnail of Department of Administration and Organization Theory

A scan through available political science and public administration literature points to a globa... more A scan through available political science and public administration literature points to a global upsurge in studies on bureaucratic autonomy. The predominant focus of most of these studies have been to either establish a framework for conceptualizing the theory of autonomy or to delve into the professionalism and autonomy of certain bureaucrats. This current study seeks to apply the Principal Agency Theory and the Bureaucrat Professionalism Theory to ascertain the independence of the ECOWAS donor funded bureaucrat. The study was qualitative in nature, adopted an exploratory research design and a purposive sampling approach. Structured interviews were administered to 10 respondents comprising 7 donor funded bureaucrat and 3 senior members of ECOWAS who were 'purposively' drawn for the study. The results of the study revealed that even though the autonomy of the ECOWAS donor funded bureaucrat is not absolute, they wield a certain level of autonomy that fits both into 'autonomy of will' and 'autonomy of action'. In much the same way, the study established that the ECOWAS donor funded bureaucrat satisfies a significant portion of professionalism standards. Additionally, this study found that Communication flaws, Economic development disparities amongst member countries and Change management are the various impediments to the professionalism of the ECOWAS donor funded bureaucrat. The study, therefore, recommends that ECOWAS should review its 12 months chairmanship tenure which tends to introduce frequent modifications into the management of ECOWAS. Again, the study recommends the establishment of a robust research unit to remedy the situation where bureaucrats struggle to access relevant data to aid decision making. To add to this, ECOWAS should commence negotiations with the professional bodies of the various donor funded bureaucrats to ensure that they implement legislations permitting the application of sanctions to professionals whose conduct falls short of acceptable standards. Purposive sampling (non-probability sampling) was employed in selecting respondents, hence the sampling frame would not have equal chance of being selected. Therefore, the findings of this study cannot be generalized to wider population of donor funded bureaucrats globally. Future research should focus on other unions using different sampling methods. Furthermore, this study employed the Principal Agent Theory (main) and Bureaucratic Professionalism Theory (Supporting) in assessing the autonomy of the ECOWAS donor funded bureaucrats. Future research should also focus on ii| P a g e the application of other models to understand the level of autonomy of the ECOWAS donor funded bureaucrat. iii| P a g e DEDICATION This thesis is dedicated to God and My Family especially My Son, Oheneba Afriyie Osei, My Wife, Barbara Obi Asante and My mum, Madam Esther Sarfo for their support and encouragement. God richly bless you all. iv| P a g e ACKNOWLEDGEMENT Am extremely grateful to the Almighty God for bringing me this far. I also wish to express my appreciation to my supervisors, Prof. Zuzana Murdoch for her mentorship and guidance throughout this study. Someway, am grateful to Prof. Ishtiaq Jamil, his guidance throughout this Master Thesis. My profound and deepest gratitude also goes to my very good friend Samuel Dobbin whose support is not measurable, Mrs.

Research paper thumbnail of Modeling Extracellular Matrix-Cell Interactions in Lung Repair and Chronic Disease

Cells, 2021

The lung extracellular matrix (ECM) is a complex and dynamic mixture of fibrous proteins (collage... more The lung extracellular matrix (ECM) is a complex and dynamic mixture of fibrous proteins (collagen, elastin), glycoproteins (fibronectin, laminin), glycosaminoglycans (heparin, hyaluronic acid) and proteoglycans (perlecan, versican), that are essential for normal lung development and organ health [...]

Research paper thumbnail of The Role Of Interleukin-1 In Driving Inflammation And Remodeling In The Asthmatic Emtu

American Journal of Respiratory and Critical Care Medicine, 2017

Research paper thumbnail of What Have In Vitro Co-Culture Models Taught Us about the Contribution of Epithelial-Mesenchymal Interactions to Airway Inflammation and Remodeling in Asthma?

Cells, 2020

As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental process... more As the lung develops, epithelial-mesenchymal crosstalk is essential for the developmental processes that drive cell proliferation, differentiation, and extracellular matrix (ECM) production within the lung epithelial-mesenchymal trophic unit (EMTU). In asthma, a number of the lung EMTU developmental signals have been associated with airway inflammation and remodeling, which has led to the hypothesis that aberrant activation of the asthmatic EMTU may lead to disease pathogenesis. Monoculture studies have aided in the understanding of the altered phenotype of airway epithelial and mesenchymal cells and their contribution to the pathogenesis of asthma. However, 3-dimensional (3D) co-culture models are needed to enable the study of epithelial-mesenchymal crosstalk in the setting of the in vivo environment. In this review, we summarize studies using 3D co-culture models to assess how defective epithelial-mesenchymal communication contributes to chronic airway inflammation and remodeling ...

Research paper thumbnail of Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma

Scientific Reports, 2020

In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role i... more In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to control...

Research paper thumbnail of An In-Situ Single Cell Atlas of the Terminal Bronchioles in Chronic Obstructive Pulmonary Disease by Imaging Mass Cytometry

C18. IMAGING MECHANISMS OF LUNG DISEASE, 2020

Research paper thumbnail of Super resolution measurement of collagen fibers in biological samples: Validation of a commercial solution for multiphoton microscopy

PLOS ONE, 2020

Multiphoton microscopy is a powerful, non-invasive technique to image biological specimens. One c... more Multiphoton microscopy is a powerful, non-invasive technique to image biological specimens. One current limitation of multiphoton microscopy is resolution as many of the biological molecules and structures investigated by research groups are similar in size or smaller than the diffraction limit. To date, the combination of multiphoton and super-resolution imaging has proved technically challenging for biology focused laboratories to implement. Here we validate that the commercial super-resolution Airyscan detector from ZEISS, which is based on image scanning microscopy, can be integrated under warranty with a pulsed multi-photon laser to enable multiphoton microscopy with super-resolution. We demonstrate its biological application in two different imaging modalities, second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), to measure the fibre thicknesses of collagen and elastin molecules surpassing the diffraction limit by a factor of 1.7±0.3x and 1.4±0.3x respectively, in human heart and lung tissues, and 3-dimensional in vitro models. We show that enhanced resolution and signal-to-noise of SHG using the Airyscan compared to traditional GaAs detectors allows for automated and precise measurement of collagen fibres using texture analysis in biological tissues.

Research paper thumbnail of Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD

European Respiratory Journal, 2019

Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality... more Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide. In the context of disease pathogenesis, both asthma and COPD involve chronic inflammation of the lung and are characterised by the abnormal release of inflammatory cytokines, dysregulated immune cell activity and remodelling of the airways. To date, current treatments still only manage symptoms and do not reverse the primary disease processes. In recent work, interleukin (IL)-1α and IL-1β have been suggested to play important roles in both asthma and COPD. In this review, we summarise overwhelming pre-clinical evidence for dysregulated signalling of IL-1α and IL-1β contributing to disease pathogenesis and discuss the paradox of IL-1 therapeutic studies in asthma and COPD. This is particularly important given recent completed and ongoing clinical trials with IL-1 biologics that have had varying degrees of failure and success as therapeutics for disease modification in asthma a...

Research paper thumbnail of miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD

The European respiratory journal, 2017

We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived infl... more We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial-mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreas...

Research paper thumbnail of Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD

European Respiratory Journal, 2016

Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesench... more Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-...

Research paper thumbnail of Unravelling the complexity of COPD by microRNAs: it's a small world after all

European Respiratory Journal, 2015

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the f... more Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking.In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future...

Research paper thumbnail of Department of Administration and Organization Theory

A scan through available political science and public administration literature points to a globa... more A scan through available political science and public administration literature points to a global upsurge in studies on bureaucratic autonomy. The predominant focus of most of these studies have been to either establish a framework for conceptualizing the theory of autonomy or to delve into the professionalism and autonomy of certain bureaucrats. This current study seeks to apply the Principal Agency Theory and the Bureaucrat Professionalism Theory to ascertain the independence of the ECOWAS donor funded bureaucrat. The study was qualitative in nature, adopted an exploratory research design and a purposive sampling approach. Structured interviews were administered to 10 respondents comprising 7 donor funded bureaucrat and 3 senior members of ECOWAS who were 'purposively' drawn for the study. The results of the study revealed that even though the autonomy of the ECOWAS donor funded bureaucrat is not absolute, they wield a certain level of autonomy that fits both into 'autonomy of will' and 'autonomy of action'. In much the same way, the study established that the ECOWAS donor funded bureaucrat satisfies a significant portion of professionalism standards. Additionally, this study found that Communication flaws, Economic development disparities amongst member countries and Change management are the various impediments to the professionalism of the ECOWAS donor funded bureaucrat. The study, therefore, recommends that ECOWAS should review its 12 months chairmanship tenure which tends to introduce frequent modifications into the management of ECOWAS. Again, the study recommends the establishment of a robust research unit to remedy the situation where bureaucrats struggle to access relevant data to aid decision making. To add to this, ECOWAS should commence negotiations with the professional bodies of the various donor funded bureaucrats to ensure that they implement legislations permitting the application of sanctions to professionals whose conduct falls short of acceptable standards. Purposive sampling (non-probability sampling) was employed in selecting respondents, hence the sampling frame would not have equal chance of being selected. Therefore, the findings of this study cannot be generalized to wider population of donor funded bureaucrats globally. Future research should focus on other unions using different sampling methods. Furthermore, this study employed the Principal Agent Theory (main) and Bureaucratic Professionalism Theory (Supporting) in assessing the autonomy of the ECOWAS donor funded bureaucrats. Future research should also focus on ii| P a g e the application of other models to understand the level of autonomy of the ECOWAS donor funded bureaucrat. iii| P a g e DEDICATION This thesis is dedicated to God and My Family especially My Son, Oheneba Afriyie Osei, My Wife, Barbara Obi Asante and My mum, Madam Esther Sarfo for their support and encouragement. God richly bless you all. iv| P a g e ACKNOWLEDGEMENT Am extremely grateful to the Almighty God for bringing me this far. I also wish to express my appreciation to my supervisors, Prof. Zuzana Murdoch for her mentorship and guidance throughout this study. Someway, am grateful to Prof. Ishtiaq Jamil, his guidance throughout this Master Thesis. My profound and deepest gratitude also goes to my very good friend Samuel Dobbin whose support is not measurable, Mrs.