WorldCat Identities

Börries, Melanie 1971-

Overview
Works: 46 works in 62 publications in 2 languages and 177 library holdings
Roles: Author, dgs, Contributor, Other
Publication Timeline
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Most widely held works by Melanie Börries
Transcriptome dynamics to unravel PC12 cell fate decisions by Barbara Offermann( )

1 edition published in 2017 in English and held by 16 WorldCat member libraries worldwide

Abstract: The PC12 cell line is a well-established cell model system for analysing cell fate decisionmaking processes. When stimulated with the growth factor EGF the cells proliferate increasingly, when stimulated with the nerve growth factor NGF the cells differentiate into sympathetic-like neurons. Both processes are regulated via the ERK/MAPK pathway. In this context, signal duration of activated ERK seems to be the key mechanism for the emergence of the distinct cell fates. Whereas NGF stimulation results in sustained ERK activation and neuronal differentiation of the cell line, EGF stimulation activates ERK transiently and results in enhanced cell proliferation. How the temporal dynamics of ERK signalling are encoded and translated in order to specify cell fates has not been fully understood yet. <br>This thesis is the first comparison of the EGF and NGF induced transcriptome of PC12 cells on a time scale of 24 hours with high sample density. It was shown that the EGF and NGF stimulus activate a very similar set of genes, which initiates and modulates the cell fate decision. These genes' expression dynamics, however, were different depending on the stimulus used: EGF stimulation induced a short impulse-like gene expression pattern, whereas NGF stimulation resulted in a long-sustained response. In line with previous studies it was demonstrated, that immediate early genes such as Egr1, Fos and Junb show an increased stability in the case of NGF stimulation. It was shown, that this is most likely due to a delayed negative transcriptional feedback via Fosl1, Atf3, Maff, Klf2 und Zfp36l2. Moreover it was demonstrated, that both cell fates, proliferation as well as differentiation, are not solely dependent on the ERK/MAPK pathway. Within the first hour after stimulation with EGF cross-talk between the MAPK and PI3K pathways seems necessary in order to induce enhanced cell proliferation. After stimulation with NGF a more complex and sequential activation of different pathways was identified. In this context the activation of the Il6 pathway and the uPA/uPAR complex seems to be of special importance. The activation of these two pathways was exclusively seen after NGF-stimulation, which encourages further research to gain a deeper understanding of their function in the process of neuronal differentiation. Additionally, Dusp6 was identified as a potentially important modulator of the PC12 cell fate. In summary, this thesis analyses and compares the EGF and NGF induced transcriptome of PC12 cells from a systems biology perspective. Most importantly, it was shown, that the activation of a similar set of genes may result in distinctly different cellular behaviour depending on the genes' expression dynamics
LungSys - Systembiologie von Lungenkrebs: dynamische Eigenschaften früher Metastasierung und therapeutische Optionen Schlussbericht : 01.02.2012-31.07.2015 by Jens Timmer( )

2 editions published in 2016 in German and held by 14 WorldCat member libraries worldwide

Requirements Analysis and Specification for a Molecular Tumor Board Platform Based on cBioPortal by Philipp Buechner( )

3 editions published in 2020 in English and held by 5 WorldCat member libraries worldwide

CREBBP is a target of epigenetic, but not genetic, modification in juvenile myelomonocytic leukemia by Silvia Fluhr( )

3 editions published in 2016 in English and held by 5 WorldCat member libraries worldwide

Abstract: Background<br><br>Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm of childhood whose clinical heterogeneity is only poorly represented by gene sequence alterations. It was previously shown that aberrant DNA methylation of distinct target genes defines a more aggressive variant of JMML, but only few significant targets are known so far. To get a broader picture of disturbed CpG methylation patterns in JMML, we carried out a methylation screen of 34 candidate genes in 45 patients using quantitative mass spectrometry.<br>Findings<br><br>Five of 34 candidate genes analyzed showed recurrent hypermethylation in JMML. cAMP-responsive element-binding protein-binding protein (CREBBP) was the most frequent target of epigenetic modification (77 % of cases). However, no pathogenic mutations of CREBBP were identified in a genetic analysis of 64 patients. CREBBP hypermethylation correlated with clinical parameters known to predict poor outcome.<br>Conclusions<br><br>This study supports the relevance of epigenetic aberrations in JMML pathophysiology. Our data confirm that DNA hypermethylation in JMML is highly target-specific and associated with higher-risk features. These findings encourage the development of prognostic markers based on epigenetic alterations, which will be helpful in the difficult clinical management of this heterogeneous disease
From a traditional medicinal plant to a rational drug: understanding the clinically proven wound healing efficacy of birch bark extract by Sandra Ebeling( )

2 editions published in 2014 in English and held by 5 WorldCat member libraries worldwide

Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures by Dirk Schumacher( )

2 editions published in 2019 in English and held by 4 WorldCat member libraries worldwide

Abstract: Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. MAPK signaling, analyzed by targeted proteomics, shows unexpected heterogeneity irrespective of RAS mutations and is associated with variable responses to EGFR inhibition. In addition, we obtained evidence for intratumoral heterogeneity in drug response among parallel "sibling" 3D cultures established from a single KRAS-mutant CRC. Our results imply that separate testing of drug effects in multiple subpopulations may help to elucidate molecular correlates of tumor heterogeneity and to improve therapy response prediction in patients
RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia by Daniel B Lipka( )

2 editions published in 2017 in English and held by 4 WorldCat member libraries worldwide

Abstract: Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML
Personalized clinical decision making through implementation of a molecular tumor board: a German single-center experience by Rouven Höfflin( )

1 edition published in 2018 in English and held by 3 WorldCat member libraries worldwide

Abstract: Purpose<br>Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment.<br><br>Methods<br>This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials.<br><br>Results<br>The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments.<br><br>Conclusion<br>Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing
HIF-1[alpha] and HIF-2[alpha] differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice by Rouven Höfflin( )

1 edition published in 2020 in English and held by 3 WorldCat member libraries worldwide

Lack of electron acceptors contributes to redox stress and growth arrest in asparagine-starved sarcoma cells by Christoph Bauer( )

1 edition published in 2021 in English and held by 3 WorldCat member libraries worldwide

Abstract: Amino acids are integral components of cancer metabolism. The non-essential amino acid asparagine supports the growth and survival of various cancer cell types. Here, different mass spectrometry approaches were employed to identify lower aspartate levels, higher aspartate/glutamine ratios and lower tricarboxylic acid (TCA) cycle metabolite levels in asparagine-deprived sarcoma cells. Reduced nicotinamide adenine dinucleotide (NAD+)/nicotinamide adenine dinucleotide hydride (NADH) ratios were consistent with redirection of TCA cycle flux and relative electron acceptor deficiency. Elevated lactate/pyruvate ratios may be due to compensatory NAD+ regeneration through increased pyruvate to lactate conversion by lactate dehydrogenase. Supplementation with exogenous pyruvate, which serves as an electron acceptor, restored aspartate levels, NAD+/NADH ratios, lactate/pyruvate ratios and cell growth in asparagine-deprived cells. Chemicals disrupting NAD+ regeneration in the electron transport chain further enhanced the anti-proliferative and pro-apoptotic effects of asparagine depletion. We speculate that reductive stress may be a major contributor to the growth arrest observed in asparagine-starved cells
Boolean modeling reveals the necessity of transcriptional regulation for bistability in PC12 cell differentiation by Barbara Offermann( )

1 edition published in 2016 in English and held by 3 WorldCat member libraries worldwide

Abstract: The nerve growth factor NGF has been shown to cause cell fate decisions toward either differentiation or proliferation depending on the relative activity of downstream pERK, pAKT, or pJNK signaling. However, how these protein signals are translated into and fed back from transcriptional activity to complete cellular differentiation over a time span of hours to days is still an open question. Comparing the time-resolved transcriptome response of NGF- or EGF-stimulated PC12 cells over 24 h in combination with protein and phenotype data we inferred a dynamic Boolean model capturing the temporal sequence of protein signaling, transcriptional response and subsequent autocrine feedback. Network topology was optimized by fitting the model to time-resolved transcriptome data under MEK, PI3K, or JNK inhibition. The integrated model confirmed the parallel use of MAPK/ERK, PI3K/AKT, and JNK/JUN for PC12 cell differentiation. Redundancy of cell signaling is demonstrated from the inhibition of the different MAPK pathways. As suggested in silico and confirmed in vitro, differentiation was substantially suppressed under JNK inhibition, yet delayed only under MEK/ERK inhibition. Most importantly, we found that positive transcriptional feedback induces bistability in the cell fate switch. De novo gene expression was necessary to activate autocrine feedback that caused Urokinase-Type Plasminogen Activator (uPA) Receptor signaling to perpetuate the MAPK activity, finally resulting in the expression of late, differentiation related genes. Thus, the cellular decision toward differentiation depends on the establishment of a transcriptome-induced positive feedback between protein signaling and gene expression thereby constituting a robust control between proliferation and differentiation
SNAIL1 employs [beta]-Catenin-LEF1 complexes to control colorectal cancer cell invasion and proliferation by Vivien Freihen( )

2 editions published between 2019 and 2020 in English and held by 3 WorldCat member libraries worldwide

Genome-wide mapping of DNA-binding sites identifies stemness-related genes as directly repressed targets of SNAIL1 in colorectal cancer cells by Sven Beyes( )

2 editions published in 2019 in English and held by 3 WorldCat member libraries worldwide

Abstract: At the molecular level, epithelial-to-mesenchymal transition (EMT) necessitates extensive transcriptional reprogramming which is orchestrated by a small group of gene-regulatory factors that include the zinc-finger DNA-binding protein SNAIL1. Although SNAIL1 is a well-known master regulator of EMT, knowledge of its immediate target genes is incomplete. Here, we used ChIP-seq to identify genes directly regulated by SNAIL1 in colorectal adenocarcinoma cells. When comparing the genomic distribution of SNAIL1 to that of the intestinal stem cell (ISC) transcription factors ASCL2 and TCF7L2, we observed a significant overlap. Furthermore, SNAIL1 ChIP-seq peaks are associated with a substantial fraction of ISC signature genes. In two colorectal cancer cell lines, we verified that SNAIL1 decreases ISC marker expression. Likewise, SNAIL1 directly represses the proto-oncogene MYB, and the long noncoding RNA (lncRNA) WiNTRLINC1, a recently described regulator of ASCL2. SNAIL1 targets multiple regulatory elements at the MYB and WiNTRLINC1 loci, and displaces ASCL2 and TCF7L2 from their binding regions at a MYB downstream regulatory element. Correlation analyses and expression profiling showed antiparallel expression of SNAIL1 and MYB in colorectal and breast cancer cell lines and tumor transcriptomes, suggesting that SNAIL1 controls MYB expression in different tissues. MYB loss-of-function attenuated proliferation and impaired clonogenicity in two- and three-dimensional cell cultures. Therefore, SNAIL1-mediated downregulation of MYB and ISC markers like WiNTRLINC1 likely contributes to the decrease in proliferation known to be associated with EMT, while simultaneously abrogating stemness features of colorectal cancer cells. Apparently, the relationship between EMT and stemness varies in different tumor entities
Alteration of proteotranscriptomic landscape reveals the transcriptional regulatory circuits controlling key-signaling pathways and metabolic reprogramming during tumor evolution by Andrieux Geoffroy( )

1 edition published in 2020 in English and held by 3 WorldCat member libraries worldwide

Abstract: The proteotranscriptomic landscape depends on the transcription, mRNA-turnover, translation, and regulated-destruction of proteins. Gene-specific mRNA-to-protein correlation is the consequence of the dynamic interplays of the different regulatory processes of proteotranscriptomic landscape. So far, the critical impact of mRNA and protein stability on their subsequent correlation on a global scale remained unresolved. Whether the mRNA-to-protein correlations are constrained by their stability and conserved across mammalian species including human is unknown. Moreover, whether the stability-dependent correlation pattern is altered in the tumor has not been explored. To establish the quantitative relationship between stability and correlation between mRNA and protein levels, we performed a multi-omics data integration study across mammalian systems including diverse types of human tissues and cell lines in a genome-wide manner. The current study illuminated an important aspect of the mammalian proteotranscriptomic landscape by providing evidence that stability-constrained mRNA-to-protein correlation follows a hierarchical pattern that remains conserved across different tissues and mammalian species. By analyzing the tumor and non-tumor tissues, we further illustrated that mRNA-to-protein correlations deviate in tumor tissues. By gene-centric analysis, we harnessed the hierarchical correlation patterns to identify altered mRNA-to-protein correlation in tumors and characterized the tumor correlation-enhancing and -repressing genes. We elucidated the transcriptional regulatory circuits controlling the correlation-enhancing and -repressing genes that are associated with metabolic reprogramming and cancer-associated pathways in tumor tissue. By tightly controlling the mRNA-to-protein correlation of specific genes, the transcriptional regulatory circuits may enable the tumor cells to evolve in varying tumor microenvironment. The mRNA-to-protein correlation analysis thus can serve as a unique approach to identify the pathways prioritized by the tumor cells at different clinical stages. The component of transcriptional regulatory circuits identified by the current study can serve as potential candidates for stage-dependent anticancer therapy
Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer by Saskia Hussung( )

1 edition published in 2021 in English and held by 3 WorldCat member libraries worldwide

Abstract: Background<br>Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19-9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters.<br><br>Methods<br>Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19-9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020.<br><br>Results<br>Out of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19-9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19-9 levels outperformed either individual marker. cfKRASmut outperformed CA 19-9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS.<br><br>Conclusions<br>Integrated analysis of cfKRASmut and CA 19-9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker's specific potential
CCL5 mediates target-kinase independent resistance to FLT3 inhibitors in FLT3-ITD-positive AML by Silvia Waldeck( )

1 edition published in 2020 in English and held by 3 WorldCat member libraries worldwide

Cardiac regeneration and tumor growth - what do they have in common? by Severin Dicks( )

1 edition published in 2020 in English and held by 3 WorldCat member libraries worldwide

Abstract: Acute myocardial infarction is a leading cause of death. Unlike most adult mammals, zebrafish have the capability to almost fully regenerate their hearts after injury. In contrast, ischemic damage in adult human and mouse hearts usually results in scar tissue. mRNA-Sequencing (Seq) and miRNA-Seq analyses of heart regeneration in zebrafish over time showed that the process can be divided into three phases: the first phase represents dedifferentiation and proliferation of cells, the second phase is characterized by migration, and in the third phase cell signals indicate heart development and differentiation. The first two phases seem to share major similarities with tumor development and growth. To gain more insight into these similarities between cardiac regeneration and tumor development and growth, we used patient matched tumor normal ("healthy") RNA-Seq data for several tumor entities from The Cancer Genome Atlas (TCGA). Subsequently, RNA data were processed using the same pipeline for both the zebrafish samples and tumor datasets. Functional analysis showed that multiple Gene Ontology terms (GO terms) are involved in both early stage cardiac regeneration and tumor development/growth across multiple tumor entities. These GO terms are mostly associated with cell cycle processes. Further analysis showed that orthologous genes are the same key players that regulated these changes in both diseases. We also observed that GO terms associated with heart development in the third late phase of cardiac regeneration are downregulated in the tumor entities. Taken together, our analysis illustrates similarities between cardiac remodeling and tumor progression
Delineating the dynamic transcriptome response of mRNA and microRNA during zebrafish heart regeneration by Hagen Klett( )

1 edition published in 2019 in English and held by 3 WorldCat member libraries worldwide

Abstract: Heart diseases are the leading cause of death for the vast majority of people around the world, which is often due to the limited capability of human cardiac regeneration. In contrast, zebrafish have the capacity to fully regenerate their hearts after cardiac injury. Understanding and activating these mechanisms would improve health in patients suffering from long-term consequences of ischemia. Therefore, we monitored the dynamic transcriptome response of both mRNA and microRNA in zebrafish at 1-160 days post cryoinjury (dpi). Using a control model of sham-operated and healthy fish, we extracted the regeneration specific response and further delineated the spatio-temporal organization of regeneration processes such as cell cycle and heart function. In addition, we identified novel (miR-148/152, miR-218b and miR-19) and previously known microRNAs among the top regulators of heart regeneration by using theoretically predicted target sites and correlation of expression profiles from both mRNA and microRNA. In a cross-species effort, we validated our findings in the dynamic process of rat myoblasts differentiating into cardiomyocytes-like cells (H9c2 cell line). Concluding, we elucidated different phases of transcriptomic responses during zebrafish heart regeneration. Furthermore, microRNAs showed to be important regulators in cardiomyocyte proliferation over time
 
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Alternative Names
Boerries, Melanie 1971-

Melanie Boerries onderzoeker

Languages
English (26)

German (5)