ORCID Profile
0000-0003-1547-1705
Current Organisations
KU Leuven
,
VIB Center for Cancer Biology
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Publisher: BMJ
Date: 22-12-2018
DOI: 10.1136/GUTJNL-2018-316888
Abstract: Acute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity. Following phenotypic characterisation, we performed RNA sequencing on CD14 + CD16 − monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function. Monocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14 + CD16 − monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores. In ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542778.V1
Abstract: Supplementary Figure 16
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542766
Abstract: Supplementary Figure 5
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542787
Abstract: Supplementary Figure 13
Publisher: Springer Science and Business Media LLC
Date: 20-11-2017
DOI: 10.1038/LEU.2017.328
Publisher: American Association for Cancer Research (AACR)
Date: 11-2020
DOI: 10.1158/2643-3230.BCD-20-0059
Abstract: We developed a DNA methylation signature that reveals the epigenetic history of thymocytes during T-cell transformation. This human signature was recapitulated by murine self-renewing preleukemic thymocytes that build an age-related CpG island hypermethylation phenotype, providing conceptual evidence for the involvement of a preleukemic thymic phase in human T-cell leukemia. This article is highlighted in the In This Issue feature, p. 215
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542769
Abstract: Supplementary Figure 4
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542760
Abstract: Supplementary Figure 7
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-07-2022
Abstract: High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or lifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542781
Abstract: Supplementary Figure 15
Publisher: American Chemical Society (ACS)
Date: 03-05-2010
DOI: 10.1021/PR1001753
Abstract: Glycosylation is a co- and/or post-translational protein modification that generates enormous structural ersity among glycoproteins. In this study, immobilized lectins were used to capture glycoproteins with different glycan profiles from Drosophila melanogaster extracts. On the basis of previous results from glycan array analyses, the snowdrop (Galanthus nivalis) agglutinin (GNA), the tobacco (Nicotiana tabacum) lectin (Nictaba) and the Rhizoctoni solani agglutinin (RSA) were used to select for a broad range of N- and O-glycan structures. After different lectin affinity chromatographies, the glycoproteome of Drosophila was analyzed using LC-MS/MS and glycoprotein abundances were calculated by different label-free methods. Bioinformatics tools were used to annotate the identified glycoproteins and the glycoproteins were classified according to their molecular function or their involvement in a biological process. Subsequent enrichment analysis (using the DAVID database) was employed to find biological processes or molecular functions in Drosophila in which a particular glycan signature is overrepresented. The results presented here clearly demonstrate that next to the presence of high-mannose and pauci-mannose N-glycans, Drosophila is capable of synthesizing glycoproteins carrying extended hybrid and complex N-linked glycans. Furthermore, it was demonstrated that a specific glycosylation signature can be associated with a functionally related group of glycoproteins in Drosophila, both in terms of biological process and molecular function.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542763
Abstract: Supplementary Figure 6
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542763.V1
Abstract: Supplementary Figure 6
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542784.V1
Abstract: Supplementary Figure 14
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542784
Abstract: Supplementary Figure 14
Publisher: Oxford University Press (OUP)
Date: 11-01-2011
Abstract: The tobacco (Nicotiana tabacum) agglutinin or Nictaba is a member of a novel class of plant lectins residing in the nucleus and the cytoplasm of tobacco cells. Since tobacco lectin expression is only observed after the plant has been subjected to stress situations such as jasmonate treatment or insect attack, Nictaba is believed to act as a signaling protein involved in the stress physiology of the plant. In this paper, a nuclear proteomics approach was followed to identify the binding partners for Nictaba in the nucleus and the cytoplasm of tobacco cv Xanthi cells. Using lectin affinity chromatography and pull-down assays, it was shown that Nictaba interacts primarily with histone proteins. Binding of Nictaba with histone H2B was confirmed in vitro using affinity chromatography of purified calf thymus histone proteins on a Nictaba column. Elution of Nictaba-interacting histone proteins was achieved with 1 m N-acetylglucosamine (GlcNAc). Moreover, mass spectrometry analyses indicated that the Nictaba-interacting histone proteins are modified by O-GlcNAc. Since the lectin-histone interaction was shown to be carbohydrate dependent, it is proposed that Nictaba might fulfill a signaling role in response to stress by interacting with O-GlcNAcylated proteins in the plant cell nucleus.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-05-2021
Abstract: Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542796.V1
Abstract: Supplementary Figure 10
Publisher: Elsevier BV
Date: 05-2019
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542775.V1
Abstract: Supplementary Figure 2
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542754.V1
Abstract: Supplementary Figure 9
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542790.V1
Abstract: Supplementary Figure 12
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542757
Abstract: Supplementary Figure 8
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542778
Abstract: Supplementary Figure 16
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542799
Abstract: Supplementary Figure 1
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542754
Abstract: Supplementary Figure 9
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542793
Abstract: Supplementary Figure 11
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542787.V1
Abstract: Supplementary Figure 13
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542760.V1
Abstract: Supplementary Figure 7
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.C.6550039
Abstract: Abstract Cancer cells display DNA hypermethylation at specific CpG islands in comparison with their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 ( i PRC2 /i ) target genes that are not expressed in normal or malignant T cells and that display a reciprocal association with H3K27me3 binding. In addition, we reveal that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in preleukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent decitabine. Altogether, we provide conceptual evidence for the involvement of a preleukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL. Significance: We developed a DNA methylation signature that reveals the epigenetic history of thymocytes during T-cell transformation. This human signature was recapitulated by murine self-renewing preleukemic thymocytes that build an age-related CpG island hypermethylation phenotype, providing conceptual evidence for the involvement of a preleukemic thymic phase in human T-cell leukemia. i This article is highlighted in the In This Issue feature, p. 215 /i /
Publisher: Public Library of Science (PLoS)
Date: 23-02-2011
Publisher: Springer Science and Business Media LLC
Date: 27-03-2017
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542790
Abstract: Supplementary Figure 12
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542775
Abstract: Supplementary Figure 2
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542769.V1
Abstract: Supplementary Figure 4
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542796
Abstract: Supplementary Figure 10
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542751
Abstract: Supplementary Tables 1-15
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542766.V1
Abstract: Supplementary Figure 5
Publisher: MDPI AG
Date: 10-10-2019
Abstract: Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542781.V1
Abstract: Supplementary Figure 15
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542772
Abstract: Supplementary Figure 3
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542793.V1
Abstract: Supplementary Figure 11
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.C.6550039.V1
Abstract: Abstract Cancer cells display DNA hypermethylation at specific CpG islands in comparison with their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 ( i PRC2 /i ) target genes that are not expressed in normal or malignant T cells and that display a reciprocal association with H3K27me3 binding. In addition, we reveal that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in preleukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent decitabine. Altogether, we provide conceptual evidence for the involvement of a preleukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL. Significance: We developed a DNA methylation signature that reveals the epigenetic history of thymocytes during T-cell transformation. This human signature was recapitulated by murine self-renewing preleukemic thymocytes that build an age-related CpG island hypermethylation phenotype, providing conceptual evidence for the involvement of a preleukemic thymic phase in human T-cell leukemia. i This article is highlighted in the In This Issue feature, p. 215 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542799.V1
Abstract: Supplementary Figure 1
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542751.V1
Abstract: Supplementary Tables 1-15
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542772.V1
Abstract: Supplementary Figure 3
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2643-3230.22542757.V1
Abstract: Supplementary Figure 8
Location: United States of America
Location: Belgium
No related grants have been discovered for Bart Ghesquière.