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3. Supplemental Figure 6: Analysis of spleens from APCMin mice. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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4. Supplemental Figure 3: High MS-444 concentrations impede intestinal epithelial re-epithelialization and induce HuR nucleocytoplasmic shuttling in an acute colitis model. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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5. Supplemental Figure 4: CRISPR/Cas9 HuR ko in RAW 264.7 macrophage cells. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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6. Supplemental Figure 2: Small intestinal crypt-villus length and HuR subcellular distribution in tumors. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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7. Supplemental Figure 1: Weight curves, DSS water consumption, colonoscopy and tumor localization in APCMin mice. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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8. Supplemental Figure 7: Chao1 and Shannon richness estimates and indicator OTUs for AOM/DSS mice. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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9. Supplemental Figure 5: Immune cell infiltration in intestinal tumors and cytokine expression in small intestinal organoids upon MS-444. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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10. Supplemental methods and references from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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11. Supplemental tables 1-3 from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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12. Supplemental Figure 8: Chao1 and Shannon richness estimates and indicator OTUs for AOM/DSS mice. from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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13. Data from HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, primary, Passecker, Katharina, primary, Mesteri, Ildiko, primary, Bhuju, Sabin, primary, Ebner, Florian, primary, Sedlyarov, Vitaly, primary, Evstatiev, Rayko, primary, Dammann, Kyle, primary, Loy, Alexander, primary, Kuzyk, Orest, primary, Kovarik, Pavel, primary, Khare, Vineeta, primary, Beibel, Martin, primary, Roma, Guglielmo, primary, Meisner-Kober, Nicole, primary, and Gasche, Christoph, primary

Published
2023
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21. Complete Genome Sequencing of Isolates from Malaysia Reveals Massive Genome Rearrangement but High Conservation of Virulence-Associated Genes

Author

Ramli, Siti Roszilawati, Bunk, Boyke, Spröer, Cathrin, Geffers, Robert, Jarek, Michael, Bhuju, Sabin, Goris, Marga, Mustakim, Sahlawati, Pessler, Frank, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.

Subjects
Leptospira, genome rearrangement, virulence, classification, whole genome, biomarker, leptospirosis, genetics, Leptospira interrogans, rfb locus, genome
Abstract

The ability of Leptospirae to persist in environments and animal hosts but to cause clinically highly variable disease in humans has made leptospirosis the most common zoonotic disease. Considering the paucity of data on variation in complete genomes of human pathogenic Leptospirae, we have used a combination of Single Molecule Real-Time (SMRT) and Illumina sequencing to obtain complete genome sequences of six human clinical L. interrogans isolates from Malaysia. All six contained the larger (4.28-4.56 Mb) and smaller (0.34-0.395 Mb) chromosome typical of human pathogenic Leptospirae and 0-7 plasmids. Only 24% of the plasmid sequences could be matched to databases. We identified a chromosomal core genome of 3318 coding sequences and strain-specific accessory genomes of 49-179 coding sequences. These sequences enabled detailed genomic strain typing (Genome BLAST Distance Phylogeny, DNA-DNA hybridization, and multi locus sequence typing) and phylogenetic classification (whole-genome SNP genotyping). Even though there was some shared synteny and collinearity across the six genomes, there was evidence of major genome rearrangement, likely driven by horizontal gene transfer and homologous recombination. Mobile genetic elements were identified in all strains in highly varying numbers, including in the rfb locus, which defines serogroups and contributes to immune escape and pathogenesis. On the other hand, there was high conservation of virulence-associated genes including those relating to sialic acid, alginate, and lipid A biosynthesis. These findings suggest (i) that the antigenic variation, adaption to various host environments, and broad spectrum of virulence of L. interrogans are in part due to a high degree of genomic plasticity and (ii) that human pathogenic strains maintain a core set of genes required for virulence.

Published
2021

24. HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, Berry, David, Passecker, Katharina, Mesteri, Ildiko, Bhuju, Sabin, Ebner, Florian, Sedlyarov, Vitaly, Evstatiev, Rayko, Dammann, Kyle, Loy, Alexander, Kuzyk, Orest, Kovarik, Pavel, Khare, Vineeta, Beibel, Martin, Roma, Guglielmo, Meisner-Kober, Nicole, Gasche, Christoph, and ZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.

Subjects
digestive system diseases
Abstract

HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of IBD and inflammatory colon cancer, augmented DSS-induced weight loss and increased tumor multiplicity, size, and invasiveness. MS-444 treatment also abrogated tumor cell apoptosis and depleted tumor-associated eosinophils, accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in APCMin mice, a model of FAP and colon cancer, diminished the number of small intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity, with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae Taken together, our results indicate that HuR activation is an early event in FAP-adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a preclinical proof of concept for HuR inhibition as an effective means of FAP chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9); 2424-38. ©2017 AACR.

Published
2017

28. Packaging of Dinoroseobacter shibae DNA into Gene Transfer Agent Particles Is Not Random

Author

Tomasch, Jürgen, primary, Wang, Hui, additional, Hall, April T K, additional, Patzelt, Diana, additional, Preusse, Matthias, additional, Petersen, Jörn, additional, Brinkmann, Henner, additional, Bunk, Boyke, additional, Bhuju, Sabin, additional, Jarek, Michael, additional, Geffers, Robert, additional, Lang, Andrew S, additional, and Wagner-Döbler, Irene, additional

Published
2018
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31. HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis

Author

Lang, Michaela, primary, Berry, David, additional, Passecker, Katharina, additional, Mesteri, Ildiko, additional, Bhuju, Sabin, additional, Ebner, Florian, additional, Sedlyarov, Vitaly, additional, Evstatiev, Rayko, additional, Dammann, Kyle, additional, Loy, Alexander, additional, Kuzyk, Orest, additional, Kovarik, Pavel, additional, Khare, Vineeta, additional, Beibel, Martin, additional, Roma, Guglielmo, additional, Meisner-Kober, Nicole, additional, and Gasche, Christoph, additional

Published
2017
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32. The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells

Author

Poppe, Michael, primary, Wittig, Sascha, additional, Jurida, Liane, additional, Bartkuhn, Marek, additional, Wilhelm, Jochen, additional, Müller, Helmut, additional, Beuerlein, Knut, additional, Karl, Nadja, additional, Bhuju, Sabin, additional, Ziebuhr, John, additional, Schmitz, M. Lienhard, additional, and Kracht, Michael, additional

Published
2017
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36. CD25 + FoxP3 + Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo

Author

Chachage, Mkunde, primary, Pollakis, Georgios, additional, Kuffour, Edmund Osei, additional, Haase, Kerstin, additional, Bauer, Asli, additional, Nadai, Yuka, additional, Podola, Lilli, additional, Clowes, Petra, additional, Schiemann, Matthias, additional, Henkel, Lynette, additional, Hoffmann, Dieter, additional, Joseph, Sarah, additional, Bhuju, Sabin, additional, Maboko, Leonard, additional, Sarfo, Fred Stephen, additional, Eberhardt, Kirsten, additional, Hoelscher, Michael, additional, Feldt, Torsten, additional, Saathoff, Elmar, additional, and Geldmacher, Christof, additional

Published
2016
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37. Sepsis Induces Specific Changes in Histone Modification Patterns in Human Monocytes

Author

Weiterer, Sebastian, Uhle, Florian, Lichtenstern, Christoph, Siegler, Benedikt H, Bhuju, Sabin, Jarek, Michael, Bartkuhn, Marek, and Weigand, Markus A

Subjects
Chromatin Immunoprecipitation, lcsh:R, Histocompatibility Antigens Class II, lcsh:Medicine, Chromatin, Monocytes, Histones, Case-Control Studies, Sepsis, Cluster Analysis, Humans, lcsh:Q, Receptors, Interleukin-1 Type II, lcsh:Science, Promoter Regions, Genetic, Protein Processing, Post-Translational, Research Article
Abstract

Background Sepsis is a global burden and the primary cause of death in intensive care units worldwide. The pathophysiological changes induced by the host’s systemic inflammatory response to infection are not yet fully understood. During sepsis, the immune system is confronted with a variety of factors, which are integrated within the individual cells and result in changes of their basal state of responsiveness. Epigenetic mechanisms like histone modifications are known to participate in the control of immune reactions, but so far the situation during sepsis is unknown. Methods and Findings In a pilot approach, we performed combined chromatin immunoprecipitation followed by high-throughput sequencing to assess the genome-wide distribution of the chromatin modifications histone 3 lysine 4 and 27 trimethylation and lysine 9 acetylation in monocytes isolated from healthy donors (n = 4) and patients with sepsis (n = 2). Despite different underlying causes for sepsis, a comparison over promoter regions shows a high correlation between the patients for all chromatin marks. These findings hold true also when comparing patients to healthy controls. Despite the global similarity, differential analysis reveals a set of distinct promoters with significant enrichment or depletion of histone marks. Further analysis of overrepresented GO terms show an enrichment of genes involved in immune function. To the most prominent ones belong different members of the HLA family located within the MHC cluster together with the gene coding for the major regulator of this locus—CIITA. Conclusions We are able to show for the first time that sepsis in humans induces selective and precise changes of chromatin modifications in distinct promoter regions of immunologically relevant genes, shedding light on basal regulatory mechanisms that might be contributing to the functional changes occurring in monocytes.

Published
2015

38. From human monocytes to genome-wide binding sites : a protocol for small amounts of blood: Monocyte Isolation/ChIP-Protocol/Library Amplification/Genome Wide Computational Data Analysis

Author

Weiterer, Sebastian, Uhle, Florian, Bhuju, Sabin, Jarek, Michael, Weigand, Markus A., Bartkuhn, Marek, and Justus Liebig University Giessen

Subjects
ddc:610
Abstract

Chromatin immunoprecipitation in combination with a genome-wide analysis via high-throughput sequencing is the state of the art method to gain genome-wide representation of histone modification or transcription factor binding profiles. However, chromatin immunoprecipitation analysis in the context of human experimental samples is limited, especially in the case of blood cells. The typically extremely low yields of precipitated DNA are usually not compatible with library amplification for next generation sequencing. We developed a highly reproducible protocol to present a guideline from the first step of isolating monocytes from a blood sample to analyse the distribution of histone modifications in a genome-wide manner. Conclusion: The protocol describes the whole work flow from isolating monocytes from human blood samples followed by a high-sensitivity and small-scale chromatin immunoprecipitation assay with guidance for generating libraries compatible with next generation sequencing from small amounts of immunoprecipitated DNA.

Published
2014
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41. Molecular Predictors of Outcome in Patients with MDS and AML Following MDS after Allogeneic Hematopoietic Stem Cell Transplantation

Author

Heuser, Michael, primary, Koenecke, Christian, additional, Gabdoulline, Razif, additional, Löffeld, Patrick, additional, Dobbernack, Vera, additional, Panagiota, Victoria, additional, Klesse, Sabrina, additional, Stadler, Michael, additional, Krauter, Juergen, additional, Dammann, Elke, additional, Wichmann, Martin, additional, Shahswar, Rabia, additional, Bhuju, Sabin, additional, Geffers, Robert, additional, Schlegelberger, Brigitte, additional, Göhring, Gudrun, additional, Kleine, Moritz, additional, Brauns, Wiebke, additional, Platzbecker, Uwe, additional, Thiede, Christian, additional, Schroeder, Thomas, additional, Kobbe, Guido, additional, Ganser, Arnold, additional, Kroeger, Nicolaus, additional, and Thol, Felicitas, additional

Published
2015
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42. A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer

Author

Eddyani, Miriam, primary, Vandelannoote, Koen, additional, Meehan, Conor J., additional, Bhuju, Sabin, additional, Porter, Jessica L., additional, Aguiar, Julia, additional, Seemann, Torsten, additional, Jarek, Michael, additional, Singh, Mahavir, additional, Portaels, Françoise, additional, Stinear, Timothy P., additional, and de Jong, Bouke C., additional

Published
2015
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46. A transferable plasticity region inCampylobacter coliallows isolates of an otherwise non-glycolytic food-borne pathogen to catabolize glucose

Author

Vorwerk, Hanne, primary, Huber, Claudia, additional, Mohr, Juliane, additional, Bunk, Boyke, additional, Bhuju, Sabin, additional, Wensel, Olga, additional, Spröer, Cathrin, additional, Fruth, Angelika, additional, Flieger, Antje, additional, Schmidt-Hohagen, Kerstin, additional, Schomburg, Dietmar, additional, Eisenreich, Wolfgang, additional, and Hofreuter, Dirk, additional

Published
2015
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48. Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice

Author

Vercauteren, Koen, primary, Brown, Richard J P, additional, Mesalam, Ahmed Atef, additional, Doerrbecker, Juliane, additional, Bhuju, Sabin, additional, Geffers, Robert, additional, Van Den Eede, Naomi, additional, McClure, C Patrick, additional, Troise, Fulvia, additional, Verhoye, Lieven, additional, Baumert, Thomas, additional, Farhoudi, Ali, additional, Cortese, Riccardo, additional, Ball, Jonathan K, additional, Leroux-Roels, Geert, additional, Pietschmann, Thomas, additional, Nicosia, Alfredo, additional, and Meuleman, Philip, additional

Published
2015
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