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33 results on '"Bleck, Bertram"'

1. A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability

Author

Apostolou, Athanasia, Panchakshari, Rohit A., Banerjee, Antara, Manatakis, Dimitris V., Paraskevopoulou, Maria D., Luc, Raymond, Abu-Ali, Galeb, Dimitriou, Alexandra, Lucchesi, Carolina, Kulkarni, Gauri, Maulana, Tengku Ibrahim, Kasendra, Magdalena, Kerns, Jordan S., Bleck, Bertram, Ewart, Lorna, Manolakos, Elias S., Hamilton, Geraldine A., Giallourakis, Cosmas, and Karalis, Katia

Published
2021
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2. High-dimensional single-cell analysis identifies cellular signatures associated with response to vedolizumab therapy in ulcerative colitis

Author

Festen, Eleonora, primary, Sun, Shiqiang, additional, Pibiri, Paola, additional, Karmi, Naomi, additional, Oelen, Roy, additional, de Jong, Sofie, additional, Bangma, Amber, additional, Teunis, Johan, additional, Kats-Ugurlu, Gursah, additional, Paraskevopoulou, Maria, additional, Farahmand, Saman, additional, Juarez, Julius, additional, Bleck, Bertram, additional, Xia, Guliang, additional, Visschedijk, Marijn, additional, Faber, Klaas, additional, Hermoso, Marcela, additional, Weersma, Rinse, additional, and Bigaeva, Emilia, additional

Published
2023
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6. A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability

Author

Apostolou, Athanasia Panchakshari, Rohit A. Banerjee, Antara and Manatakis, V, Dimitris Paraskevopoulou, Maria D. Luc, Raymond and Abu-Ali, Galeb Dimitriou, Alexandra Lucchesi, Carolina and Kulkarni, Gauri Maulana, Tengku Ibrahim Kasendra, Magdalena and Kerns, Jordan S. Bleck, Bertram Ewart, Lorna Manolakos, Elias S. Hamilton, Geraldine A. Giallourakis, Cosmas and Karalis, Katia

Abstract

BACKGROUND & AIMS: The limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed to mimic properties of human intestinal epithelium leading to insights into barrier integrity. METHODS: We combined the human biopsy-derived leucine-rich repeat-containing G-protein-coupled receptor 5-positive organoids and Organ-on-Chip technologies to establish a micro-engineered human Colon Intestine-Chip (Emulate, Inc, Boston, MA). We characterized the proximity of the model to human tissue and organoids maintained in suspension by RNA sequencing analysis, and their differentiation to intestinal epithelial cells on the Colon Intestine-Chip under variable conditions. Furthermore, organoids from different donors were evaluated to understand variability in the system. Our system was applied to understanding the epithelial barrier and characterizing mechanisms driving the cytokine-induced barrier disruption. RESULTS: Our data highlight the importance of the endothelium and the in vivo tissue-relevant dynamic microenvironment in the Colon Intestine-Chip in the establishment of a tight monolayer of differentiated, polarized, organoid-derived intestinal epithelial cells. We confirmed the effect of interferon-gamma on the colonic barrier and identified reorganization of apical junctional complexes, and induction of apoptosis in the intestinal epithelial cells as mediating mechanisms. We show that in the human Colon Intestine-Chip exposure to interleukin 22 induces disruption of the barrier, unlike its described protective role in experimental colitis in mice. CONCLUSIONS: We developed a human Colon Intestine-Chip platform and showed its value in the characterization of the mechanism of action of interleukin 22 in the human epithelial barrier. This system can be used to elucidate, in a time- and challenge-dependent manner, the mechanism driving the development of leaky gut in human beings and to identify associated biomarkers.

Published
2021

9. A Micro-engineered Human Colon Intestine-Chip Platform to Study Leaky Barrier

Author

Apostolou, Athanasia, primary, Panchakshari, Rohit A., additional, Banerjee, Antara, additional, Manatakis, Dimitris V., additional, Paraskevopoulou, Maria D., additional, Luc, Raymond, additional, AbuAli, Galeb, additional, Dimitriou, Alexandra, additional, Lucchesi, Carolina, additional, Kulkarni, Gauri, additional, Maulana, Tengku Ibrahim, additional, Bleck, Bertram, additional, Manolakos, Elias S., additional, Hamilton, Geraldine A., additional, Giallourakis, Cosmas, additional, and Karalis, Katia, additional

Published
2020
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19. Genetic Variants of TSLP and Asthma in an Admixed Urban Population

Author

Liu, Mengling, primary, Rogers, Linda, additional, Cheng, Qinyi, additional, Shao, Yongzhao, additional, Fernandez-Beros, Maria Elena, additional, Hirschhorn, Joel N., additional, Lyon, Helen N., additional, Gajdos, Zofia K. Z., additional, Vedantam, Sailaja, additional, Gregersen, Peter, additional, Seldin, Michael F., additional, Bleck, Bertram, additional, Ramasamy, Adaikalavan, additional, Hartikainen, Anna-Liisa, additional, Jarvelin, Marjo-Riitta, additional, Kuokkanen, Mikko, additional, Laitinen, Tarja, additional, Eriksson, Johan, additional, Lehtimäki, Terho, additional, Raitakari, Olli T., additional, and Reibman, Joan, additional

Published
2011
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32. Genetic Variants of TSLP and Asthma in an Admixed Urban Population.

Author

Mengling Liu, Rogers, Linda, Qinyi Cheng, Yongzhao Shao, Fernandez-Beros, Maria Elena, Hirschhorn, Joel N., Lyon, Helen N., Gajdos, Zofia K. Z., Vedantam, Sailaja, Gregersen, Peter, Seldin, Michael F., Bleck, Bertram, Ramasamy, Adaikalavan, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Kuokkanen, Mikko, Laitinen, Tarja, Eriksson, Johan, Lehtimäki, Terho, and Raitakari, Olli T.

Subjects
ASTHMA diagnosis, CITY dwellers, THYMIC stromal lymphopoietin, CYTOKINES, ASTHMATICS, EPITHELIAL cells, GENETIC regulation
Abstract

Background: Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations. Objectives: To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. Methodology and Main Results: Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09-2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04-3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93-1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10-2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07-1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08-1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94-1.17, p = 0.33). Conclusions: Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction. [ABSTRACT FROM AUTHOR]

Published
2011
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33. Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs.

Author

Grunig G, Baghdassarian A, Park SH, Pylawka S, Bleck B, Reibman J, Berman-Rosenzweig E, and Durmus N

Abstract

This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling.

Published
2016
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