The Experts below are selected from a list of 143403 Experts worldwide ranked by ideXlab platform
Bertram Klinger - One of the best experts on this subject based on the ideXlab platform.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy. KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
bioRxiv, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Gieseckethiel, Silvia SchulzeAbstract:Abstract Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative Network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Florian Uhlitz - One of the best experts on this subject based on the ideXlab platform.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy. KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
bioRxiv, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Gieseckethiel, Silvia SchulzeAbstract:Abstract Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative Network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Shane D Johnson - One of the best experts on this subject based on the ideXlab platform.
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examining the relationship between road structure and burglary risk via Quantitative Network analysis
Journal of Quantitative Criminology, 2015Co-Authors: Toby Davies, Shane D JohnsonAbstract:Objectives To test the hypothesis that the spatial distribution of residential burglary is shaped by the configuration of the street Network, as predicted by, for example, crime pattern theory. In particular, the study examines whether burglary risk is higher on street segments with higher usage potential.
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examining the relationship between road structure and burglary risk via Quantitative Network analysis
Journal of Quantitative Criminology, 2015Co-Authors: Toby Davies, Shane D JohnsonAbstract:To test the hypothesis that the spatial distribution of residential burglary is shaped by the configuration of the street Network, as predicted by, for example, crime pattern theory. In particular, the study examines whether burglary risk is higher on street segments with higher usage potential. Residential burglary data for Birmingham (UK) are examined at the street segment level using a hierarchical linear model. Estimates of the usage of street segments are derived from the graph theoretical metric of betweenness, which measures how frequently segments feature in the shortest paths (those most likely to be used) through the Network. Several variants of betweenness are considered. The geometry of street segments is also incorporated—via a measure of their linearity—as are several socio-demographic factors. As anticipated by theory, the measure of betweenness was found to be a highly-significant predictor of the burglary victimization count at the street segment level for all but one of the variants considered. The non-significant result was found for the most localized measure of betweenness considered. More linear streets were generally found to be at lower risk of victimization. Betweenness offers a more granular and objective means of measuring the street Network than categorical classifications previously used, and its meaning links more directly to theory. The results provide support for crime pattern theory, suggesting a higher risk of burglary for streets with more potential usage. The apparent negative effect of linearity suggests the need for further research into the visual component of target choice, and the role of guardianship.
Mareen Luthen - One of the best experts on this subject based on the ideXlab platform.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy. KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
bioRxiv, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Gieseckethiel, Silvia SchulzeAbstract:Abstract Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative Network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Thomas Sell - One of the best experts on this subject based on the ideXlab platform.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
Nature Communications, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram KlingerAbstract:Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRASG12V in mouse intestinal organoids, while transgenic BRAFV600E activates ERK in all cells. Quantitative Network modelling from perturbation data reveals that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identify dual-specificity phosphatases as candidate modulators of ERK in the intestine. Furthermore, we find that oncogenic KRAS, together with β-Catenin, favours expansion of crypt cells with high ERK activity. Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy. KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.
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cell type dependent differential activation of erk by oncogenic kras in colon cancer and intestinal epithelium
bioRxiv, 2019Co-Authors: Raphael Brandt, Thomas Sell, Mareen Luthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Gieseckethiel, Silvia SchulzeAbstract:Abstract Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative Network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
