Author: "Emmanuelle Soleilhac" - Searchworks@Jio Institute Digital Library Search Results

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33 results on '"Emmanuelle Soleilhac"'

1. Identification of chemicals breaking the USP8 interaction with its endocytic substrate CHMP1B

Author: Agnès Journet, Caroline Barette, Laurence Aubry, Emmanuelle Soleilhac, and Marie-Odile Fauvarque
Subjects: Drug discovery, Endocytosis, High-throughput screening, MIT domain, ESCRT, Protein-protein interaction, Medicine (General), R5-920, Biotechnology, TP248.13-248.65
Abstract: The ubiquitin-specific protease USP8 plays a major role in controlling the stability and intracellular trafficking of numerous cell surface proteins among which the EGF receptor that regulates cell growth and proliferation in many physio-pathological processes. The function of USP8 at the endocytic pathway level partly relies on binding to and deubiquitination of the Endosomal Sorting Complex Required for Transport (ESCRT) protein CHMP1B. In the aim of finding chemical inhibitors of the USP8::CHMP1B interaction, we performed a high-throughput screening campaign using an HTRF® assay to monitor the interaction directly in lysates of cells co-expressing both partners. The assay was carried out in an automated format to screen the academic Fr-PPIChem library (Bosc N et al., 2020), which includes 10,314 compounds dedicated to the targeting of protein-protein interactions (PPIs). Eleven confirmed hits inhibited the USP8::CHMP1B interaction within a range of 30% to 70% inhibition at 50 µM, while they were inactive on a set of other PPI interfaces demonstrating the feasibility of specifically disrupting this particular interface. In parallel, we adapted this HTRF® assay to compare the USP8 interacting capacity of CHMP1B variants. As anticipated from earlier studies, a deletion of the MIM (Microtubule Interacting and Trafficking domain Interacting Motif) domain or mutation of two conserved leucine residues, L192 and L195, in this domain respectively abolished or strongly impeded the USP8::CHMP1B interaction. By contrast, a CHMP1B mutant that displays a highly decreased ubiquitination level following mutation of four lysine residues in arginine interacted at a similar level as the wild-type form with USP8. Therefore, conserved leucine residues within the MIT domain rather than its ubiquitinated status triggers CHMP1B substrate recognition by USP8.
Published: 2022
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2. NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway

Author: Déborah Reynaud, Nadia Alfaidy, Constance Collet, Nicolas Lemaitre, Frederic Sergent, Céline Miege, Emmanuelle Soleilhac, Alaa Al Assi, Padma Murthi, Gilles Courtois, Marie-Odile Fauvarque, Rima Slim, Mohamed Benharouga, and Roland Abi Nahed
Subjects: NLRP7, inflammasome, gestational choriocarcinoma, camouflage, NF-κB, cancer, Cytology, QH573-671
Abstract: Background: Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). NLRP7 is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7 can function in an inflammasome-dependent or -independent pathway. Recently, we have demonstrated that NLRP7 is highly expressed in GC tumor cells and contributes to their tumorigenesis. However, the underlying mechanisms are still unknown. Here, we investigated the mechanism by which NLRP7 controls these processes in malignant (JEG-3) and non-tumor (HTR8/SVneo) trophoblastic cells. Cell survival, dedifferentiation, camouflage, and aggressiveness were compared between normal JEG-3 cells or knockdown for NLRP7, JEG-3 Sh NLRP7. In addition, HTR8/SVneo cells overexpressing NLRP7 were used to determine the impact of NLRP7 overexpression on non-tumor cells. NLRP7 involvement in tumor cell growth and tolerance was further characterized in vivo using the metastatic mouse model of GC. Results: We demonstrate that NLRP7 (i) functions in an inflammasome-dependent and -independent manners in HTR8/SVneo and JEG-3 cells, respectively; (ii) differentially regulates the activity of NF-κB in tumor and non-tumor cells; (iii) increases malignant cell survival, dedifferentiation, and camouflage; and (iv) facilitates tumor cells colonization of the lungs in the preclinical model of GC. Conclusions: This study demonstrates for the first time the mechanism by which NLRP7, independently of its inflammasome machinery, contributes to GC growth and tumorigenesis. The clinical relevance of NLRP7 in this rare cancer highlights its potential therapeutic promise as a molecular target to treat resistant GC patients.
Published: 2023
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3. Investigation of Chemical Composition and Biological Activities of Ajuga pyramidalis—Isolation of Iridoids and Phenylethanoid Glycosides

Author: Anthonin Gori, Benjamin Boucherle, Aurélien Rey, Maxime Rome, Caroline Barette, Emmanuelle Soleilhac, Christian Philouze, Marie-Odile Fauvarque, Nicola Fuzzati, and Marine Peuchmaur
Subjects: Ajuga pyramidalis, chemical composition, iridoids, phenylethanoid glycosides, antioxidant, epidermal renewal, Microbiology, QR1-502
Abstract: Despite several studies on the Ajuga L. genus, the chemical composition of Ajuga pyramidalis, an alpine endemic species, is still largely unknown. The purpose of this study was to therefore deeper describe it, particularly from the phytochemistry and bioactivity perspectives. In that respect, A. pyramidalis was investigated and 95% of the extracted mass of the plant was characterized by chromatography and mass spectrometry. Apart from the already determined chemical compounds, namely, harpagide and 8-O-acetylharpagide, two iridoids, and neoajugapyrin A, a neo-clerodane diterpene, and three polyphenols (echinacoside, verbascoside and teupoloside) were identified for the first time in A. pyramidalis. Incidentally, the first RX structure of a harpagoside derivative is also described in this paper. The extracts and isolated compounds were then evaluated for various biochemical or biological activities; notably a targeted action on the renewal of the epidermis was highlighted with potential applications in the cosmetic field for anti-aging.
Published: 2023
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4. BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Author: Marie Ouarné, Claire Bouvard, Gabriela Boneva, Christine Mallet, Johnny Ribeiro, Agnès Desroches-Castan, Emmanuelle Soleilhac, Emmanuelle Tillet, Olivier Peyruchaud, and Sabine Bailly
Subjects: BMP9, BMP10, Tumor angiogenesis, E0771, Mammary tumor, Metastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Angiogenesis has become an attractive target for cancer therapy. However, despite the initial success of anti-VEGF (Vascular endothelial growth factor) therapies, the overall survival appears only modestly improved and resistance to therapy often develops. Other anti-angiogenic targets are thus urgently needed. The predominant expression of the type I BMP (bone morphogenetic protein) receptor ALK1 (activin receptor-like kinase 1) in endothelial cells makes it an attractive target, and phase I/II trials are currently being conducted. ALK1 binds with strong affinity to two ligands that belong to the TGF-ß family, BMP9 and BMP10. In the present work, we addressed their specific roles in tumor angiogenesis, cancer development and metastasis in a mammary cancer model. Methods For this, we used knockout (KO) mice for BMP9 (constitutive Gdf2-deficient), for BMP10 (inducible Bmp10-deficient) and double KO mice (Gdf2 and Bmp10) in a syngeneic immunocompetent orthotopic mouse model of spontaneous metastatic breast cancer (E0771). Results Our studies demonstrate a specific role for BMP9 in the E0771 mammary carcinoma model. Gdf2 deletion increased tumor growth while inhibiting vessel maturation and tumor perfusion. Gdf2 deletion also increased the number and the mean size of lung metastases. On the other hand, Bmp10 deletion did not significantly affect the E0771 mammary model and the double deletion (Gdf2 and Bmp10) did not lead to a stronger phenotype than the single Gdf2 deletion. Conclusions Altogether, our data show that in a tumor environment BMP9 and BMP10 play different roles and thus blocking their shared receptor ALK1 is maybe not appropriate. Indeed, BMP9, but not BMP10, acts as a quiescence factor on tumor growth, lung metastasis and vessel normalization. Our results also support that activating rather than blocking the BMP9 pathway could be a new strategy for tumor vessel normalization in order to treat breast cancer.
Published: 2018
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5. CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis.

Author: Xènia Crespo-Yàñez, Carmen Aguilar-Gurrieri, Anne-Claire Jacomin, Agnès Journet, Magda Mortier, Emmanuel Taillebourg, Emmanuelle Soleilhac, Winfried Weissenhorn, and Marie-Odile Fauvarque
Subjects: Genetics, QH426-470
Abstract: Integration and down-regulation of cell growth and differentiation signals rely on plasma membrane receptor endocytosis and sorting towards either recycling vesicles or degradative lysosomes via multivesicular bodies (MVB). In this process, the endosomal sorting complex-III required for transport (ESCRT-III) controls membrane deformation and scission triggering intraluminal vesicle (ILV) formation at early endosomes. Here, we show that the ESCRT-III member CHMP1B can be ubiquitinated within a flexible loop known to undergo conformational changes during polymerization. We demonstrate further that CHMP1B is deubiquitinated by the ubiquitin specific protease USP8 (syn. UBPY) and found fully devoid of ubiquitin in a ~500 kDa large complex that also contains its ESCRT-III partner IST1. Moreover, EGF stimulation induces the rapid and transient accumulation of ubiquitinated forms of CHMP1B on cell membranes. Accordingly, CHMP1B ubiquitination is necessary for CHMP1B function in both EGF receptor trafficking in human cells and wing development in Drosophila. Based on these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane-associated ESCRT-III polymer.
Published: 2018
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6. The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.

Author: Anne-Claire Jacomin, Amandine Bescond, Emmanuelle Soleilhac, Benoît Gallet, Guy Schoehn, Marie-Odile Fauvarque, and Emmanuel Taillebourg
Subjects: Medicine, Science
Abstract: Autophagy is a catabolic process that delivers cytoplasmic components to the lysosomes. Protein modification by ubiquitination is involved in this pathway: it regulates the stability of autophagy regulators such as BECLIN-1 and it also functions as a tag targeting specific substrates to autophagosomes. In order to identify deubiquitinating enzymes (DUBs) involved in autophagy, we have performed a genetic screen in the Drosophila larval fat body. This screen identified Uch-L3, Usp45, Usp12 and Ubpy. In this paper, we show that Ubpy loss of function results in the accumulation of autophagosomes due to a blockade of the autophagy flux. Furthermore, analysis by electron and confocal microscopy of Ubpy-depleted fat body cells revealed altered lysosomal morphology, indicating that Ubpy inactivation affects lysosomal maintenance and/or biogenesis. Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells affects autophagy in a different way: in UBPY-depleted HeLa cells autophagy is deregulated.
Published: 2015
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7. Supplementary Video 1 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: MOV file - 6MB, Effect of Pyr1 on microtubule dynamic instability - Time-lapse microscopy after 2 hours of incubation, on GFP-EB3 HeLa cells treated with DMSO (control), 5 muM, 10 muM or 25 muM Pyr1, as indicated. 4.Supplementary information
Published: 2023
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8. Supplementary Figure 2 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 486K, Analysis of the consequence of actin filaments depolymerization on Pyr1 -induced formation of Detyr-microtubules
Published: 2023
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9. Supplementary Figure 1 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 212K, Effect of Pyr1 treatment on the number and on the size of EB1 comets in HeLa cells
Published: 2023
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10. Supplementary Figure 3 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 173K, Characterization of Pyr1 (Pyr1) effects on the inhibition of LIMKs activity in vitro
Published: 2023
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11. Supplementary Figure 5 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 487K, Effects of Pyr1 structural analogues on F-actin organization, on Detyr-microtubules generation, and on in cellulo cofilin phosphorylation
Published: 2023
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12. Supplementary Figure 4 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 252K, Effect of Pyr1 on NEK11 and MLK1 activity
Published: 2023
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13. Supplementary Tables 1-9, Movie Legend, Methods from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 253K
Published: 2023
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14. Supplementary Figure 6 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

Author: Laurence Lafanechère, Ora Bernard, Stefan Knapp, Jean-Claude Florent, Diane Braguer, Charles Dumontet, Attilio Di Pietro, Rong Li, Juliana Antonipillai, David Grierson, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Anne Beghin, Odile Filhol, Emmanuelle Soleilhac, Caroline Barette, Chloé Prunier, Anne Martinez, Catherine Pillet, Chi-Hung Nguyen, Emilie Vassal-Stermann, and Renaud Prudent
Abstract: PDF file - 173K, Effect of LIMK down regulation on Detyr-tubulin levels
Published: 2023
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15. Investigation of chemical composition and biological activities of $Ajuga\ pyramidalis$—isolation of iridoids and phenylethanoid glycosides

Author: Anthonin Gori, Benjamin Boucherle, Aurélien Rey, Maxime Rome, Caroline Barette, Emmanuelle Soleilhac, Christian Philouze, Marie-Odile Fauvarque, Nicola Fuzzati, Marine Peuchmaur, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Chanel Parfums Beauté, Chanel, Jardin du Lautaret : découverte et sciences (Lautaret), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Genetics and Chemogenomics (GenChem), Laboratoire Biosciences et bioingénierie pour la santé (BGE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de Chimie Moléculaire (DCM), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), and ANR-15-IDEX-0002,UGA,IDEX UGA(2015)
Subjects: antioxidant, iridoids, Endocrinology, Diabetes and Metabolism, Ajuga pyramidalis, chemical composition, [CHIM]Chemical Sciences, phenylethanoid glycosides, epidermal renewal, Molecular Biology, Biochemistry
Abstract: International audience; Despite several studies on the Ajuga L. genus, the chemical composition of $Ajuga\ pyramidalis$, an alpine endemic species, is still largely unknown. The purpose of this study was to therefore deeper describe it, particularly from the phytochemistry and bioactivity perspectives. In that respect, $A.\ pyramidalis$ was investigated and 95% of the extracted mass of the plant was characterized by chromatography and mass spectrometry. Apart from the already determined chemical compounds, namely, harpagide and 8-O-acetylharpagide, two iridoids, and neoajugapyrin A, a neo-clerodane diterpene, and three polyphenols (echinacoside, verbascoside and teupoloside) were identified for the first time in $A.\ pyramidalis$. Incidentally, the first RX structure of a harpagoside derivative is also described in this paper. The extracts and isolated compounds were then evaluated for various biochemical or biological activities; notably a targeted action on the renewal of the epidermis was highlighted with potential applications in the cosmetic field for anti-aging.
Published: 2023
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16. Quantitative Automated Assays in Living Cells to Screen for Inhibitors of Hemichannel Function

Author: Anaelle da Costa, Magda Mortier, Marie-Odile Fauvarque, Marjorie Comte, Franck Mouthon, Caroline Barette, Emmanuelle Soleilhac, Mathieu Charvériat, Laurence Aubry, Christèle Picoli, Genetics and Chemogenomics (GenChem ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Theranexus [Lyon], and Soleilhac, Emmanuelle
Subjects: 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cell, Gene Expression, Biochemistry, Analytical Chemistry, 0302 clinical medicine, RNA, Small Interfering, Benzoxazoles, Chemistry, Drug discovery, Quinolinium Compounds, Gap junction, Transmembrane protein, 3. Good health, Cell biology, medicine.anatomical_structure, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carbenoxolone, Molecular Medicine, Biological Assay, Neuroglia, Intracellular, Biotechnology, Prescription Drugs, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Time-Lapse Imaging, drug discovery, high-content screening (HCS), central nervous system (CNS), 03 medical and health sciences, Bacterial Proteins, Downregulation and upregulation, Cell Line, Tumor, Extracellular, medicine, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Fluorescent Dyes, Automation, Laboratory, Meclofenamic Acid, hemichannel (HC), Cell Membrane, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Drugs, Investigational, Iodides, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Luminescent Proteins, 030104 developmental biology, Connexin 43, connexin (Cx), [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Calcium, sense organs, 030217 neurology & neurosurgery, Function (biology)
Abstract: International audience; In vertebrates, intercellular communication is largely mediated by connexins (Cx), a family of structurally related transmembrane proteins that assemble to form hemichannels (HCs) at the plasma membrane. HCs are upregulated in different brain disorders and represent innovative therapeutic targets. Identifying modulators of Cx-based HCs is of great interest to better understand their function and define new treatments. In this study, we developed automated versions of two different cell-based assays to identify new pharmacological modulators of Cx43-HCs. As HCs remain mostly closed under physiological conditions in cell culture, depletion of extracellular Ca 2+ was used to increase the probability of opening of HCs. The first assay follows the incorporation of a fluorescent dye, Yo-Pro, by real-time imaging, while the second is based on the quenching of a fluorescent protein, YFP QL , by iodide after iodide uptake. These assays were then used to screen a collection of 2242 approved drugs and compounds under development. This study led to the identification of 11 candidate hits blocking Cx43-HC, active in the two assays, with 5 drugs active on HC but not on gap junction (GJ) activities. To our knowledge, this is the first screening on HC activity and our results suggest the potential of a new use of already approved drugs in central nervous system disorders with HC impairments.
Published: 2021
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17. Intensity quantile estimation and mapping - a novel algorithm for the correction of image non-uniformity bias in HCS data.

Author: Ernest Lo, Emmanuelle Soleilhac, Anne Martinez, Laurence Lafanechère, and Robert Nadon
Published: 2012
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18. Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

Author: Yann Wallez, Laurent Guyon, Caroline Roelants, Christophe Battail, Q. Franquet, Frédéric Chalmel, Irinka Séraudie, Claude Cochet, Caroline Barette, Odile Filhol, Sofia Giacosa, Nicolas Peilleron, Marie-Odile Fauvarque, Catherine Pillet, Emmanuelle Soleilhac, Clément Sarrazin, Bertrand Evrard, Gaelle Fiard, Jean-Luc Descotes, Jean-Alexandre Long, BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Invasion mechanisms in angiogenesis and cancer (IMAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Inovarion, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Genetics and Chemogenomics (GenChem), CHU Grenoble, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-GMCAO), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), UMR1036, Institut National de la Santé et de la Recherche Médicale, 2018, Groupement des Entreprises Françaises dans la lutte contre le Cancer, Isère, Ligue Contre le Cancer, 2017, Association Française d'Urologie, 2019, Centre Hospitalier Universitaire de Grenoble Alpes, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Chard-Hutchinson, Xavier
Subjects: Cancer Research, kinase inhibitor, CK2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, urologic and male genital diseases, lcsh:RC254-282, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, NOX4, 03 medical and health sciences, 0302 clinical medicine, Mediator, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, ROS pathway, tumor tissue slices, 030304 developmental biology, 0303 health sciences, Kinase, ccRCC, apoptosis, Cancer, HIF-2α, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Clear cell renal cell carcinoma, Oncology, Apoptosis, Cell culture, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, ATM, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ex vivo
Abstract: Simple Summary Renal cell carcinoma (RCC) is the eighth leading malignancy in the world, accounting for 4% of all cancers with poor outcome when metastatic. Protein kinases are highly druggable proteins, which are often aberrantly activated in cancers. The aim of our study was to identify candidate targets for metastatic clear cell renal cell carcinoma therapy, using chemo-genomic-based high-throughput screening. We found that the combined inhibition of the CK2 and ATM kinases in renal tumor cells and patient-derived tumor samples induces synthetic lethality. Mechanistic investigations unveil that this drug combination triggers apoptosis through HIF-2α-(Hypoxic inducible factor HIF-2α) dependent reactive oxygen species (ROS) overproduction, giving a new option for patient care in metastatic RCC. Abstract Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL− cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug–gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.
Published: 2021
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19. MultiplePseudomonasspecies secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death

Author: Pauline Basso, Thomas Henry, Emmanuelle Soleilhac, Sylvie Elsen, Ina Attree, Pierre Wallet, and Eric Faudry
Subjects: 0301 basic medicine, biology, Pseudomonas aeruginosa, 030106 microbiology, Pyroptosis, Inflammasome, biology.organism_classification, medicine.disease_cause, Microbiology, Pseudomonas putida, Type three secretion system, 03 medical and health sciences, Pseudomonas protegens, 030104 developmental biology, medicine, Secretion, Pseudomonas entomophila, Ecology, Evolution, Behavior and Systematics, medicine.drug
Abstract: Pathogenic bacteria secrete protein toxins that provoke apoptosis or necrosis of eukaryotic cells. Here, we developed a live-imaging method, based on incorporation of a DNA-intercalating dye into membrane-damaged host cells, to study the kinetics of primary bone marrow-derived macrophages (BMDMs) mortality induced by opportunistic pathogen Pseudomonas aeruginosa expressing either Type III Secretion System (T3SS) toxins or the pore-forming toxin, Exolysin (ExlA). We found that ExlA promotes the activation of Caspase-1 and maturation of interleukin-1β. BMDMs deficient for Caspase-1 and Caspase-11 were resistant to ExlA-induced death. Furthermore, by using KO BMDMs, we determined that the upstream NLRP3/ASC complex leads to the Caspase-1 activation. We also demonstrated that Pseudomonas putida and Pseudomonas protegens and the Drosophila pathogen Pseudomonas entomophila, which naturally express ExlA-like toxins, are cytotoxic toward macrophages and provoke the same type of pro-inflammatory death as does ExlA+ P. aeruginosa. These results demonstrate that ExlA-like toxins of two-partner secretion systems from diverse Pseudomonas species activate the NLRP3 inflammasome and provoke inflammatory pyroptotic death of macrophages.
Published: 2017
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20. High-Content Screening Identifies New Inhibitors of Connexin 43 Gap Junctions

Author: Caroline Barette, Christèle Picoli, Agnès Journet, Marie-Odile Fauvarque, Emmanuelle Soleilhac, Franck Mouthon, Christian Giaume, Mathieu Charvériat, Marjorie Comte, Theranexus [Lyon], Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: 0303 health sciences, Dose-Response Relationship, Drug, Chemistry, [SDV]Life Sciences [q-bio], Gap junction, Connexin, Gap Junctions, 030226 pharmacology & pharmacy, Transmembrane protein, 3. Good health, Cell biology, High-Throughput Screening Assays, Mefloquine, 03 medical and health sciences, 0302 clinical medicine, High-content screening, Cell Line, Tumor, Connexin 43, Drug Discovery, Molecular Medicine, Humans, Cytoskeleton, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Gap junctions (GJs) are dynamic structures composed of hexamers of connexins (Cxs), a class of transmembrane proteins enabling channel-mediated direct intercellular communication through cell-cell diffusion of ions and small metabolites. In defined conditions, Cxs also work as hemichannels allowing exchanges between the cytoplasm and the extracellular medium. The most common GJ channel is formed by connexin 43 (Cx43) and plays an important role in physiological and pathological processes in excitable tissues, such as heart and brain. Hence, Cx43 has been largely envisioned as a new therapeutic target in cancer, neurological and psychiatric indications, or cardiovascular diseases. Identifying new pharmacological inhibitors of Cx43 GJs with different mechanisms of action and from diverse chemical classes is thus highly challenging. We present here a high-content screening method, based on the evaluation of fluorescent dye transfer rates between adjacent cells to monitor the function of GJs in U251 glioblastoma cells expressing high levels of Cx43. This assay was validated using well-described pharmacological GJ inhibitors such as mefloquine. The method was adapted to screen a library of 1,280 Food and Drug Administration- and European Medicines Agency-approved drugs that led to the selection of both known and new inhibitors of GJ channel function. We further focused on a specific class of microtubule-targeting agents, confirming that a proper tubulin network is required for functional Cx43 GJ channels.
Published: 2019
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21. Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

Author: Véronique Roussel, Bastien Touquet, Isabelle Tardieux, Emmanuelle Soleilhac, Caroline Barette, Dragos Horvath, Laurence Lafanechère, Eric Maréchal, Loraine Brillet-Guéguen, Renaud Prudent, Sylvaine Roy, Marylin Vantard, Cyrille Y. Botté, Vinod Kasam, Samia Aci-Sèche, Sheena Dass, Vincent Breton, Anne Imberty, Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (ABIMS), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Dynamique cellulaire et membranaire des interactions hôte-parasite (Equipe de recherche), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Atip-Avenir and Finovi programs (CNRS-INSERM-Finovi Atip-Avenir Apicolipid projects), ANR-05-CIGC-0008,DOCK,Conformation Sampling and Docking on Girds(2005), ANR-12-PDOC-0028,ApicoLipid,ApicoLipid: Etude du rôle de l'apicoplaste dans la synthèse lipidique et la biogénèse des parasites Apicomplexa(2012), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ABiMS - Informatique et bioinformatique = Analysis and Bioinformatics for Marine Science (FR2424), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Mutations des activités, des espaces et des formes d'organisation dans les territoires ruraux (METAFORT), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-ENITA Clermont-AgroParisTech-Institut National de la Recherche Agronomique (INRA), Transduction du signal : signalisation calcium, phosphorylation et inflammation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Corpusculaire - Clermont-Ferrand (LPC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA)-Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), ANR-11-LABX-0024/11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Imberty, Anne, Programme de recherche 'Calcul Intensif et Grilles de Calcul' - Conformation Sampling and Docking on Girds - - DOCK2005 - ANR-05-CIGC-0008 - CIGC - VALID, Retour Post-Doctorant - ApicoLipid: Etude du rôle de l'apicoplaste dans la synthèse lipidique et la biogénèse des parasites Apicomplexa - - ApicoLipid2012 - ANR-12-PDOC-0028 - PDOC - VALID, and Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID
Subjects: Models, Molecular, 0301 basic medicine, tubuline, cell-based assays, Protein Conformation, [SDV]Life Sciences [q-bio], Dinitroaniline, Microtubules, lcsh:Chemistry, chemistry.chemical_compound, Tubulin, [CHIM] Chemical Sciences, Arabidopsis thaliana, Photosynthesis, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Spectroscopy, biology, cellule végétale, food and beverages, General Medicine, Plants, dinitroanilines, plant cells, Toxoplasma gondii, Plasmodium falciparum, virtual screening, small molecules, 3. Good health, Computer Science Applications, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, In silico, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Catalysis, Inorganic Chemistry, Apicomplexa, 03 medical and health sciences, Microtubule, parasitic diseases, Animals, Humans, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, Virtual screening, fungi, Organic Chemistry, dinitroaniline, biology.organism_classification, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, biology.protein, HeLa Cells
Abstract: Dinitroanilines are chemical compounds with high selectivity for plant cell &alpha, tubulin in which they promote microtubule depolymerization. They target &alpha, tubulin regions that have diverged over evolution and show no effect on non-photosynthetic eukaryotes. Hence, they have been used as herbicides over decades. Interestingly, dinitroanilines proved active on microtubules of eukaryotes deriving from photosynthetic ancestors such as Toxoplasma gondii and Plasmodium falciparum, which are responsible for toxoplasmosis and malaria, respectively. By combining differential in silico screening of virtual chemical libraries on Arabidopsis thaliana and mammal tubulin structural models together with cell-based screening of chemical libraries, we have identified dinitroaniline related and non-related compounds. They inhibit plant, but not mammalian tubulin assembly in vitro, and accordingly arrest A. thaliana development. In addition, these compounds exhibit a moderate cytotoxic activity towards T. gondii and P. falciparum. These results highlight the potential of novel herbicidal scaffolds in the design of urgently needed anti-parasitic drugs.
Published: 2018
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22. Force et spécificité du criblage pour des molécules bioactives au CMBA-Grenoble

Author: Marie-Odile Fauvarque, Caroline Barette, Emmanuelle Soleilhac, Céline Charavay, and Claude Cochet
Subjects: Physics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, General Medicine, Humanities, General Biochemistry, Genetics and Molecular Biology, 030304 developmental biology
Abstract: Utilisees comme sondes chimiques, les molecules bioactives possedent un champ d’application qui inclut et depasse leur valorisation comme medicaments et met en exergue l’art d’utiliser des molecules pour decouvrir de nouvelles informations sur le vivant. La plate-forme de criblage CMBA localisee a Grenoble effectue des cribles robotises sur cellules vivantes ou sur proteines purifiees, et caracterise l’activite de molecules chimiques par imagerie automatisee. Tous les domaines d’application en biologie, sante ou environnement sont concernes, avec d’ores et deja des molecules selectionnees pour leur potentiel dans les domaines de la sante (cancer, maladies infectieuses) ou des bioenergies.
Published: 2015
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23. Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules

Author: Caroline Barette, Renaud Prudent, Catherine Pillet, Laurence Lafanechère, Emilie Vassal-Stermann, Emmanuelle Soleilhac, Anne Martinez, Attilio Di Pietro, Gustavo Jabor Gozzi, Marie-Odile Fauvarque, Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Cancer Research, Cell Survival, [SDV]Life Sciences [q-bio], Protein subunit, Cell, Cell Culture Techniques, Fluorescent Antibody Technique, Antineoplastic Agents, Biology, Microtubules, Microtubule polymerization, Tubulin, Microtubule, In vivo, Drug Discovery, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Pharmacology, Cell Cycle, Tubulin Modulators, 3. Good health, Cell biology, medicine.anatomical_structure, Oncology, Drug Design, biology.protein, Pharmacophore, Signal transduction, HeLa Cells
Abstract: International audience; Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents. These synthetic compounds do not affect the assembly state of purified microtubules in vitro but they profoundly suppress microtubule dynamics in vivo. Moreover, they exert cytotoxic effects on several cancer cell lines including multidrug resistant cell lines. Therefore, these classes of compounds represent novel attractive leads for cancer chemotherapy.
Published: 2015
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24. CLIQ-BID: A method to quantify bacteria-induced damage to eukaryotic cells by automated live-imaging of bright nuclei

Author: Stéphanie Bouillot, Ina Attree, Emmanuelle Soleilhac, Yann Wallez, Philippe Huber, Eric Faudry, Pathogénie bactérienne et réponses cellulaires, Centre National de la Recherche Scientifique (CNRS) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Biologie du Cancer et de l'Infection (BCI - UMR S1036), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Grenoble Alpes (UGA), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Grenoble Alpes [Saint Martin d'Hères] - Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Genetics and Chemogenomics (GenChem), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), AVIESAN T3SS (ANR PRP1.4), IBiSA, ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-15-CE11-0018,HemoPseudo,Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence(2015), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Faudry, Eric, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, and Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence - - HemoPseudo2015 - ANR-15-CE11-0018 - AAPG2015 - VALID
Subjects: 0301 basic medicine, Programmed cell death, 030106 microbiology, Cell, lcsh:Medicine, Virulence, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Bacterial growth, Bacterial Physiological Phenomena, medicine.disease_cause, Article, Mice, 03 medical and health sciences, Live cell imaging, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, lcsh:Science, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, lcsh:R, Endothelial Cells, Pathogenic bacteria, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Molecular Imaging, 3. Good health, Cell biology, Eukaryotic Cells, 030104 developmental biology, medicine.anatomical_structure, NIH 3T3 Cells, lcsh:Q, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Ex vivo, Bacteria, HeLa Cells
Abstract: Pathogenic bacteria induce eukaryotic cell damage which range from discrete modifications of signalling pathways, to morphological alterations and even to cell death. Accurate quantitative detection of these events is necessary for studying host-pathogen interactions and for developing strategies to protect host organisms from bacterial infections. Investigation of morphological changes is cumbersome and not adapted to high-throughput and kinetics measurements. Here, we describe a simple and cost-effective method based on automated analysis of live cells with stained nuclei, which allows real-time quantification of bacteria-induced eukaryotic cell damage at single-cell resolution. We demonstrate that this automated high-throughput microscopy approach permits screening of libraries composed of interference-RNA, bacterial strains, antibodies and chemical compounds in ex vivo infection settings. The use of fluorescently-labelled bacteria enables the concomitant detection of changes in bacterial growth. Using this method named CLIQ-BID (Cell Live Imaging Quantification of Bacteria Induced Damage), we were able to distinguish the virulence profiles of different pathogenic bacterial species and clinical strains.
Published: 2018
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25. Les criblages phénotypiques ou comment faire d’une pierre deux coups

Author: Emmanuelle Soleilhac, Laurence Lafanechère, Caroline Barette, Marie-Odile Fauvarque, and Renaud Prudent
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, General Medicine, Biology, Humanities, General Biochemistry, Genetics and Molecular Biology, 3. Good health, 030304 developmental biology
Abstract: Les criblages phenotypiques visent a identifier des molecules capables d’interferer avec une fonction cellulaire d’interet a partir de collections de molecules chimiques directement testees sur les cellules en culture. C’est une strategie risquee, mais puissante, pour decouvrir a la fois de nouvelles cibles therapeutiques et leurs regulateurs pharmacologiques. Forts d’une experience de pres de 10 ans dans ce domaine, nous soulignons dans cet article les avantages et les difficultes inherents a ce type d’approche, et presentons des solutions pour surmonter plusieurs types d’obstacles. Une communaute scientifique nationale s’est structuree autour de diverses approches de criblage que nous presentons egalement.
Published: 2013
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26. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities

Author: Caroline Barette, Attilio Di Pietro, Glaucio Valdameri, Emmanuelle Soleilhac, Agnès Desroches-Castan, Renaud Prudent, Chi-Hung Nguyen, Catherine Pillet, Marc Billaud, Jean-Jacques Feige, Marjorie Mollaret, Anne Martinez, Laurence Lafanechère, Emilie Vassal-Stermann, Jean-Claude Florent, and Jean P. Viallet
Subjects: Pharmacology, 0303 health sciences, Angiogenesis, Tubulin Modulators, Cell, Biology, 3. Good health, Microtubule polymerization, Endothelial stem cell, 03 medical and health sciences, Chorioallantoic membrane, 0302 clinical medicine, medicine.anatomical_structure, Tubulin, In vivo, 030220 oncology & carcinogenesis, medicine, biology.protein, 030304 developmental biology
Abstract: Background and Purpose Drugs targeting microtubules are commonly used for cancer treatment. However, the potency of microtubule inhibitors used clinically is limited by the emergence of resistance. We thus designed a strategy to find new cell-permeable microtubule-targeting agents. Experimental Approach Using a cell-based assay designed to probe for microtubule polymerization status, we screened a chemical library and identified two azaindole derivatives, CM01 and CM02, as cell-permeable microtubule-depolymerizing agents. The mechanism of the anti-tumour effects of these two compounds was further investigated both in vivo and in vitro. Key Results CM01 and CM02 induced G2/M cell cycle arrest and exerted potent cytostatic effects on several cancer cell lines including multidrug-resistant (MDR) cell lines. In vitro experiments revealed that the azaindole derivatives inhibited tubulin polymerization and competed with colchicines for this effect, strongly indicating that tubulin is the cellular target of these azaindole derivatives. In vivo experiments, using a chicken chorioallantoic xenograft tumour assay, established that these compounds exert a potent anti-tumour effect. Furthermore, an assay probing the growth of vessels out of endothelial cell spheroids showed that CM01 and CM02 exert anti-angiogenic activities. Conclusions and Implications CM01 and CM02 are reversible microtubule-depolymerizing agents that exert potent cytostatic effects on human cancer cells of diverse origins, including MDR cells. They were also shown to inhibit angiogenesis and tumour growth in chorioallantoic breast cancer xenografts. Hence, these azaindole derivatives are attractive candidates for further preclinical investigations.
Published: 2013
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27. [Strength and specificity of the CMBA screening platform for bioactive molecules discovery]

Author: Caroline, Barette, Emmanuelle, Soleilhac, Céline, Charavay, Claude, Cochet, and Marie-Odile, Fauvarque
Subjects: Small Molecule Libraries, Data Interpretation, Statistical, Drug Discovery, Drug Evaluation, Preclinical, Database Management Systems, Humans, France, Molecular Targeted Therapy, Sensitivity and Specificity
Abstract: Used as powerful chemical probes in Life science fundamental research, the application potential of new bioactive molecular entities includes but extends beyond their development as therapeutic drugs in pharmacology. In this review, we wish to point out the methodology of chemical libraries screening on living cells or purified proteins at the CMBA academic platform of Grenoble Alpes University, and strategies employed to further characterize the selected bioactive molecules by phenotypic profiling on human cells. Multiple application fields are concerned by the screening activity developed at CMBA with bioactive molecules previously selected for their potential as tools for fundamental research purpose, therapeutic candidates to treat cancer or infection, or promising compounds for production of bioenergy.
Published: 2015

28. Criblage phénotypique à haut contenu pour la chémobiologie et ses enjeux

Author: Elaine DEL NERY, Emmanuelle Soleilhac, Priscille Brodin, Nathalie Deboosere, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Political science, [SDV]Life Sciences [q-bio], General Medicine, Humanities, General Biochemistry, Genetics and Molecular Biology, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Le high content screening (HCS), connu en France sous le terme de « criblage a haut contenu », est apparu au cours des annees 1990 et represente une technologie innovante permettant l’evaluation des composes destines a devenir des futurs medicaments. Le HCS fut initialement concu pour elargir la comprehension du mecanisme d’action des composes en testant directement leur bioactivite sur des cellules cultivees en laboratoire. Au cours des dix dernieres annees, le champ d’utilisation du HCS s’est considerablement etendu au sein des laboratoires de recherche academiques. La technologie est ainsi devenue le point de depart de nombreux programmes d’etudes fonctionnelles visant a comprendre, pour une pathologie donnee, les cibles proteiques ou les grandes fonctions cellulaires sur lesquelles de futurs medicaments pourraient agir. Cette approche de criblage repose sur l’acquisition d’images en fluorescence de cellules marquees, ce qui genere d’enormes quantites de donnees qui doivent etre traitees par analyse d’images automatisee, et stockees de maniere appropriee. Le stockage, l’analyse et la visualisation des donnees associes a leur integration et leur interpretation sont encore des defis omnipresents auxquels la methodologie HCS doit faire face.
Published: 2015
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29. [Phenotypic screens or one stone to kill two birds: discover the target and its pharmacological regulator]

Author: Renaud, Prudent, Emmanuelle, Soleilhac, Caroline, Barette, Marie-Odile, Fauvarque, and Laurence, Lafanechère
Subjects: Small Molecule Libraries, Phenotype, Drug Evaluation, Preclinical, Humans, France, Molecular Targeted Therapy, Algorithms, High-Throughput Screening Assays
Abstract: Phenotypic screens, in which chemical libraries are assayed on cells with the aim to isolate compounds that interfere with a given cell function, are a risky but powerful strategy to discover, in the same approach, new therapeutic targets and the compounds able to regulate them. With a strong experience of nearly 10 years in the field, we present the advantages of such an approach, the possible troubles and technical solutions. We also present in this paper a french network which has been recently built and that gather all the competencies needed for screening approaches.
Published: 2013

30. High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments

Author: Laurence Lafanechère, Robert Nadon, Emmanuelle Soleilhac, Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives (GPMS / CMBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genome Quebec Innovation Center, Dept Human Genetics, McGill University, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), CEA Grenoble/DSV, McGill University = Université McGill [Montréal, Canada], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Computer science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], spheroids, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, high-content screening, 01 natural sciences, Field (computer science), 03 medical and health sciences, Basic research, Drug Discovery, single-cell analysis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 010405 organic chemistry, Drug discovery, high-content analysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Data science, 3. Good health, 0104 chemical sciences, High-content screening, embryonic structures, data reduction
Abstract: International audience; Importance of the field: Screening compounds with cell-based assays and microscopy image-based analysis is an approach currently favored for drug discovery. Because of its high information yield, the strategy is called high-content screening (HCS). Areas covered in this review: This review covers the application of HCS in drug discovery and also in basic research of potential new pathways that can be targeted for treatment of pathophysiological diseases. HCS faces several challenges, however, including the extraction of pertinent information from the massive amount of data generated from images. Several proposed approaches to HCS data acquisition and analysis are reviewed. What the reader will gain: Different solutions from the fields of mathematics, bioinformatics and biotechnology are presented. Potential applications and limits of these recent technical developments are also discussed. Take home message: HCS is a multidisciplinary and multistep approach for understanding the effects of compounds on biological processes at the cellular level. Reliable results depend on the quality of the overall process and require strong interdisciplinary collaborations.
Published: 2012
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31. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities

Author: Renaud, Prudent, Émilie, Vassal-Stermann, Chi-Hung, Nguyen, Marjorie, Mollaret, Jean, Viallet, Agnès, Desroches-Castan, Anne, Martinez, Caroline, Barette, Catherine, Pillet, Glaucio, Valdameri, Emmanuelle, Soleilhac, Attilio, Di Pietro, Jean-Jacques, Feige, Marc, Billaud, Jean-Claude, Florent, and Laurence, Lafanechère
Subjects: Indoles, Neovascularization, Pathologic, Endothelial Cells, Antineoplastic Agents, Cell Cycle Checkpoints, Chick Embryo, Xenograft Model Antitumor Assays, Research Papers, Chorioallantoic Membrane, Drug Resistance, Multiple, Tubulin Modulators, Tumor Burden, Drug Resistance, Neoplasm, Cell Line, Tumor, Neoplasms, Animals, Humans, Cells, Cultured
Abstract: Drugs targeting microtubules are commonly used for cancer treatment. However, the potency of microtubule inhibitors used clinically is limited by the emergence of resistance. We thus designed a strategy to find new cell-permeable microtubule-targeting agents.Using a cell-based assay designed to probe for microtubule polymerization status, we screened a chemical library and identified two azaindole derivatives, CM01 and CM02, as cell-permeable microtubule-depolymerizing agents. The mechanism of the anti-tumour effects of these two compounds was further investigated both in vivo and in vitro.CM01 and CM02 induced G2/M cell cycle arrest and exerted potent cytostatic effects on several cancer cell lines including multidrug-resistant (MDR) cell lines. In vitro experiments revealed that the azaindole derivatives inhibited tubulin polymerization and competed with colchicines for this effect, strongly indicating that tubulin is the cellular target of these azaindole derivatives. In vivo experiments, using a chicken chorioallantoic xenograft tumour assay, established that these compounds exert a potent anti-tumour effect. Furthermore, an assay probing the growth of vessels out of endothelial cell spheroids showed that CM01 and CM02 exert anti-angiogenic activities.CM01 and CM02 are reversible microtubule-depolymerizing agents that exert potent cytostatic effects on human cancer cells of diverse origins, including MDR cells. They were also shown to inhibit angiogenesis and tumour growth in chorioallantoic breast cancer xenografts. Hence, these azaindole derivatives are attractive candidates for further preclinical investigations.
Published: 2012

32. Pharmacological inhibition of LIM Kinase stabilizes microtubules and inhibits neoplastic growth

Author: Jean-Claude Florent, Diane Braguer, Stefan Knapp, Caroline Barette, Chi Hung Nguyen, Laurence Lafanechère, Attilio Di Pietro, Emmanuelle Soleilhac, Juliana Antonipillai, Odile Filhol, Anne Martinez, Anne Beghin, Ora Bernard, Renaud Prudent, Charles Dumontet, Emilie Vassal-Stermann, David S. Grierson, Chloé Prunier, Rong Li, Catherine Pillet, Samia Aci-Sèche, Stéphane Honoré, Glaucio Valdameri, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Albert Bonniot, Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives (GPMS / CMBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CEA Grenoble/DSV, Transduction du signal : signalisation calcium, phosphorylation et inflammation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division Matériaux et Structures de Chaussées, Laboratoire Central des Ponts et Chaussées (LCPC), Bases moléculaires et structurales des systèmes infectieux (BMSSI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. (CSVB), Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université de Lyon, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Genetics and Chemogenomics (GenChem), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), and University of Oxford
Subjects: Cancer Research, Cell Survival, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Microfilament, Microtubules, Microtubule polymerization, Lim kinase, Mice, chemistry.chemical_compound, Tubulin, Neoplasms, Animals, Humans, Cytoskeleton, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Pyr1, biology, Protein Stability, Lim Kinases, Cofilin, Actin cytoskeleton, Actins, Tubulin Modulators, Cell biology, Phenotype, Oncology, chemistry, Drug Resistance, Neoplasm, biology.protein, Female, HeLa Cells
Abstract: The emergence of tumor resistance to conventional microtubule-targeting drugs restricts their clinical use. Using a cell-based assay that recognizes microtubule polymerization status to screen for chemicals that interact with regulators of microtubule dynamics, we identified Pyr1, a cell permeable inhibitor of LIM kinase, which is the enzyme that phosphorylates and inactivates the actin-depolymerizing factor cofilin. Pyr1 reversibly stabilized microtubules, blocked actin microfilament dynamics, inhibited cell motility in vitro and showed anticancer properties in vivo, in the absence of major side effects. Pyr1 inhibition of LIM kinase caused a microtubule-stabilizing effect, which was independent of any direct effects on the actin cytoskeleton. In addition, Pyr1 retained its activity in multidrug-resistant cancer cells that were resistant to conventional microtubule-targeting agents. Our findings suggest that LIM kinase functions as a signaling node that controls both actin and microtubule dynamics. LIM kinase may therefore represent a targetable enzyme for cancer treatment. Cancer Res; 72(17); 4429–39. ©2012 AACR.
Published: 2012
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33. Parthenolide Inhibits Tubulin Carboxypeptidase Activity

Author: Emmanuelle Soleilhac, Bruno David, Jean-Christophe Cintrat, Frédéric Ausseil, Laurence Lafanechère, Véronique Masson, Caroline Barette, Georges Massiot, Xavier Fonrose, Isabelle Pouny, Bernard Rousseau, Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives (GPMS / CMBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherches en Technologies et Sciences pour le Vivant (IRTSV), Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), PIERRE FABRE-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Diagnosing, Recommending Actions and Modelling (DREAM), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Chimie des Substances Naturelles Bioactives (CSNB), Service de Chimie Bio-Organique et de Marquage (SCBM), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Chimie-Physique (LCP), Université de Cocody, Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Monash Indigenous Centre, SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and INSERM U366
Subjects: Cancer Research, Paclitaxel, Tubulin—tyrosine ligase, [SDV.CAN]Life Sciences [q-bio]/Cancer, Carboxypeptidases, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tubulin, Microtubule, Detyrosination, Humans, Drug Interactions, Parthenolide, Mitosis, 030304 developmental biology, 0303 health sciences, biology, NF-kappa B, 3. Good health, Cell biology, Spindle apparatus, Oncology, Biochemistry, chemistry, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, Sesquiterpenes, HeLa Cells
Abstract: Microtubules are centrally involved in cell division, being the principal components of mitotic spindle. Tubulin, the constituent of microtubules, can be cyclically modified on its α-subunit by enzymatic removal of the COOH-terminal tyrosine residue by an ill-defined tubulin carboxypeptidase (TCP) and its readdition by tubulin tyrosine ligase (TTL). We and others have previously shown that suppression of TTL and resulting accumulation of detyrosinated tubulin are frequent in human cancers of poor prognosis. Explanations for the involvement of TTL and detyrosinated tubulin in tumor progression arise from the recent discovery that tubulin detyrosination leads to CAP-Gly protein mislocalization, which correlates with defects in spindle positioning during mitosis. Impaired control of spindle positioning is one factor favoring tumor invasiveness. Thus, TCP could be a target for developing novel therapeutic strategies against advanced stages of cancers. Inhibitors of TCP, by reversing abnormal detyrosinated tubulin accumulation in tumor cells, could impair tumor progression. TCP has never been isolated and this has hampered search of specific inhibitors. In this article, we describe a cell-based assay of TCP activity and its use to screen a library of natural extracts for their inhibitory potency. This led to the isolation of two sesquiterpene lactones. We subsequently found that parthenolide, a structurally related compound, can efficiently inhibit TCP. This inhibitory activity is a new specific property of parthenolide independent of its action on the nuclear factor-κB pathway. Parthenolide is also known for its anticancer properties. Thus, TCP inhibition could be one of the underlying mechanisms of these anticancer properties. [Cancer Res 2007;67(7):3371–8]
Published: 2007
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33 results on '"Emmanuelle Soleilhac"'

1. Identification of chemicals breaking the USP8 interaction with its endocytic substrate CHMP1B

2. NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway

3. Investigation of Chemical Composition and Biological Activities of Ajuga pyramidalis—Isolation of Iridoids and Phenylethanoid Glycosides

4. BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

5. CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis.

6. The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.

7. Supplementary Video 1 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

8. Supplementary Figure 2 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

9. Supplementary Figure 1 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

10. Supplementary Figure 3 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

11. Supplementary Figure 5 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

12. Supplementary Figure 4 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

13. Supplementary Tables 1-9, Movie Legend, Methods from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

14. Supplementary Figure 6 from Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

15. Investigation of chemical composition and biological activities of $Ajuga\ pyramidalis$—isolation of iridoids and phenylethanoid glycosides

16. Quantitative Automated Assays in Living Cells to Screen for Inhibitors of Hemichannel Function

17. Intensity quantile estimation and mapping - a novel algorithm for the correction of image non-uniformity bias in HCS data.

18. Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

19. MultiplePseudomonasspecies secrete exolysin-like toxins and provoke Caspase-1-dependent macrophage death

20. High-Content Screening Identifies New Inhibitors of Connexin 43 Gap Junctions

21. Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

22. Force et spécificité du criblage pour des molécules bioactives au CMBA-Grenoble

23. Novel Synthetic Pharmacophores Inducing a Stabilization of Cellular Microtubules

24. CLIQ-BID: A method to quantify bacteria-induced damage to eukaryotic cells by automated live-imaging of bright nuclei

25. Les criblages phénotypiques ou comment faire d’une pierre deux coups

26. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities

27. [Strength and specificity of the CMBA screening platform for bioactive molecules discovery]

28. Criblage phénotypique à haut contenu pour la chémobiologie et ses enjeux

29. [Phenotypic screens or one stone to kill two birds: discover the target and its pharmacological regulator]

30. High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments

31. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities

32. Pharmacological inhibition of LIM Kinase stabilizes microtubules and inhibits neoplastic growth

33. Parthenolide Inhibits Tubulin Carboxypeptidase Activity

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33 results on '"Emmanuelle Soleilhac"'

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