References of "Thiry, Marc"
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See detailDUSP3 Phosphatase Deficiency or Inhibition Limits Platelet Activation and Arterial Thrombosis
Rahmouni, Souad ULg; MUSUMECI, Lucia ULg; Kuijpers, Marijke J et al

Conference (2015, June 24)

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See detailSpatio-temporal dynamics of β-tubulin isotypes and acetyl-alpha tubulin during the development of the sensory auditory organ in rodents.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2015, June 05)

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These ... [more ▼]

The auditory organ is a highly specialized structure composed by specific cellular types. The sensory cells are characterized by stereocilia at their apex and are necessary for the sound perception. These cells are supported by supporting cells. Supporting cells possess a characteristic cytoskeleton in direct relation with their morphological features and their development. There are different β-tubulin isoforms in microtubules of vertebrate tissues. However, their functional significance is still largely unknown. In the present study, we investigated the localization of five β-tubulin isotypes (β 1 to 5) as well as acetyl-α-tubulin within the hearing organ during development in rodents. By using confocal microscopy, we showed that with the exception of the β3-tubulin isoform that was specific to nerve fibres, all the different β-tubulin isoforms and acetyl-α-tubulin were mainly present in the supporting cells. Contrary to β1-4-tubulins, we also found that the β5-tubulin isoform appeared only at a key stage of the postnatal development in specific cell types (pillar cells and Deiters’ cells). By using transmission electron microscopy, we revealed further that this developmental stage coincided with the formation of two separate bundles of microtubules from a unique one in these supporting cells. In conclusion, these results suggest that the β5-tubulin isoform might be involved in the generation of new microtubule bundles from a pre-existing one. [less ▲]

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See detailVaricella-Zoster Virus (VZV) assemblons interplay with PML bodies
Lebrun, Marielle ULg; Thiry, Marc ULg; Sadzot, Catherine ULg

Poster (2015, May 15)

Using a virus expressing the small capsid protein fused to an eGFP tag (eGFP-ORF23 VZV), we recently identified, in the nuclei of infected cells, the presence of dynamic capsid aggegrates. Because we ... [more ▼]

Using a virus expressing the small capsid protein fused to an eGFP tag (eGFP-ORF23 VZV), we recently identified, in the nuclei of infected cells, the presence of dynamic capsid aggegrates. Because we believe that these structures might represent sites of preferential caspid assembly and by analogy with HSV-1, we referred to them as “VZV assemblons”. Structures resembling these assemblons and identified as capsids entrapped in some “PML-cages” were recently described in the nuclei of wild-type VZV infected cells (Reichelt et al., 2011). We then wonder if there was a link between these independent observations. When we infected MeWo cells in which the expression of each PML subunit is downregulated by shRNA, VZV assemblons still formed. Immunostaining of MeWo cells infected by eGFP-ORF23 VZV with an antibody against the PML protein showed that VZV assemblons only partially colocalize with PML bodies. However, overexpression of PML-I-eGFP in HEK293 cells followed by infection with a tagRFP-T-ORF23 VZV, where the ORF23 protein is fused to a red tag, showed a complete colocalization is complete. The same result was obtained with all tested PML isoforms. This suggests that the partial colocalization in normal cells could be due to the expression level of PML proteins. Altogether, these results suggest that rather than a progressive accumulation of newly formed capsids within PML cages, it is likely that PML protein is recruited to the sites where VZV assemblons develop. It correlates with the fact that the number of PML bodies decreases with the infection. Obviously, even if this phenomenon might impede the egress of a substantial amount of capsids and, in this regard, limit the infection progression, all the tested cell lines are permissive to VZV. It would then be interesting to investigate the relationship between VZV assemblons and PML bodies in latent or non permissive VZV infection models. [less ▲]

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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (2015), 131(7), 656-68

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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See detailMyoferlin: an indispensable component in VEGFA secretion by pancreas cancer cells
Fahmy, Karim ULg; Peulen, Olivier ULg; Castronovo, Vincenzo ULg et al

Poster (2015, January 31)

In this poster, our laboratory showed the importance of myoferlin, a biomarker of pancreas cancer, in the controle of VEGF-A mediated angiogenesis. Our laboratory showed that silencing myoferlin in ... [more ▼]

In this poster, our laboratory showed the importance of myoferlin, a biomarker of pancreas cancer, in the controle of VEGF-A mediated angiogenesis. Our laboratory showed that silencing myoferlin in pancreas cancer cells, BxPC-3, provoques a decrease in cell prolifération in vitro and a decrease in tumor volumes in animal model. Myoferlin silencing also provokes a decrease in VEGF-A secretion in the conditioned medium and that decrease was abserved in the animal model as a decrease in microvessels dencity. It appeared that this decrease in secretion is due to a a blockage in the exocytosis. Our data also showed a significate correlation between myoferlin expression and microvessels density in patients section. [less ▲]

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See detailMyoferlin Regulates Endosomal Trafficking and Tunes Cancer Cell Metabolism
Blomme, Arnaud; Costanza, Brunella; Thiry, Marc ULg et al

Poster (2015, January 31)

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See detailBacterial DNA mimetics activate platelets and promote thrombosis via CLEC-2
Delierneux, Céline; Hego, Alexandre; Lecut, Christelle et al

Poster (2015, January 27)

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See detailAccumulation of methylglyoxal, a glycolysis by-product modulates YAP1 transcription co-factor localization and activity in human breast cancer cells through HSP90 modification
Nokin, Marie-Julie; Durieux, Florence; Peixoto, Paul et al

Poster (2015, January 27)

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See detailMyoferlin: an indispensable component in VEGR-A secretion by pancreatic cancer cell
Fahmy, Karim; Gonzalez, Arnaud; Arafad, Mohamed et al

Poster (2015, January 27)

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See detailMyoferlin regulates endosomal trafficking and tunes cancer cell metabolism
Blomme, Arnaud; Costanza, Brunella; Thiry, Marc ULg et al

Poster (2015, January 27)

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See detailLocalization of rDNA transcription sites within reptilian nucleoli
Bartholomé, Odile ULg; Franck, Claire; Thiry, Marc ULg

Poster (2015, January 27)

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See detailChange in the protofilamentnumber and β5-tubulin appearance in supporting cells during development of the hearing organ.
Renauld, Justine ULg; Thelen, Nicolas ULg; Johnen, Nicolas ULg et al

Poster (2015, January)

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a ... [more ▼]

The supporting cells of the hearing organ are characterized by the presence of an abundant cytoskeleton which is mainly composed of microtubules. These supporting cells have also been shown to contain a minor mammalian tubulin, the β5-tubulin, recently reported as a biomarker of cell proliferation. It was shown that a β-tubulin isoform can specify the microtubule architecture, as seen with the expression of the Moth β2 tubulin in the Drosophila testes which imposes the 16-protofilament (16pf) structure on the corresponding subset of Drosophila microtubules. Moreover, supporting cell microtubules are formed by 15pf instead of the canonical 13, a unique fact among vertebrates. Such a protofilament configuration has been observed in C. elegans’ neurons which are responsible for the mechanosensory sense of touch. It was also shown that these 15pf microtubules were essential to the proper functioning of these neurons. To determine the role of this particular tubulin in the auditory organ and its possible involvement in the formation of the unusual 15pf microtubules of supporting cells, we studied the spatiotemporal localization of β5-tubulin during development in rats from embryonic day 18 until P25 (25th postnatal day). Then we examined the fine structure of microtubules at the transmission electron microscope level (TEM). Our results showed that β5-tubulin, contrary to other β-tubulins, had a unique distribution in the cochlea. This β-tubulin appeared at a postnatal stage, before the opening of the Corti’s tunnel and is restricted to supporting cells, especially in pillar and Deiters’ cells. Our TEM study further indicated that these cells were composed by 13pf microtubules at P2, but by 15pf microtubules at P25. In conclusion, the architecture and composition of microtubules present in the supporting cells change during development of the Corti organ. Further experiments are now required to determine if these changes are related to the appearance of β5-tubulin. [less ▲]

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See detailA dynamic unfolded protein response contributes to the control of cortical neurogenesis
LAGUESSE, Sophie ULg; Creppe, Catherine ULg; Nedialkova, Dany et al

in Developmental Cell (2015)

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See detailMicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5.
Huyghe, Aurelia; Van Den Ackerveken, Priscilla ULg; SACHELI, Rosalie ULg et al

in Cell Reports (2015), 13

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the ... [more ▼]

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the specification of these progenitors remain elusive. In the present study, by combining microarray analyses with conditional deletion of Dicer in the developing inner ear, we identified that miR-124 controls cell fate in the developing organ of Corti. By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also the PCP-related non-canonical Wnt pathways that contribute to HC differentiation and polarization in the organ of Corti. Thus, our work emphasizes the importance of miR-124 as an epigenetic safeguard that fine-tunes the expression of genes critical for cell patterning during cochlear differentiation. [less ▲]

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See detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULg; Blomme, Benoît ULg; Freres, Pierre ULg et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

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See detailDetection of rRNA synthesis sites within reptilian nucleoli
Bartholomé, Odile ULg; Thiry, Marc ULg; Franck, Claire

Poster (2014, December 13)

Detailed reference viewed: 37 (7 ULg)