ProFi Achievements
Publications
2018 |
Jonckheere, Julie; Deloulme, Jean-Christophe; Dall'Igna, Gaëlle; Chauliac, Nicolas; Pelluet, Albane; Nguon, Anne-Sophie; Lentini, Celia; Brocard, Jacques; Denarier, Eric; Brugière, Sabine; Couté, Yohann; Heinrich, Christophe; Porcher, Christophe; Holtzmann, Jérôme; Andrieux, Annie; Suaud-Chagny, Marie-Françoise; Gory-Fauré, Sylvie Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival (Article de journal) Brain Stimulation, 11 (6), p. 1336–1347, 2018, ISSN: 1876-4754. @article{jonckheere_short-_2018, title = {Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival}, author = {Julie Jonckheere and Jean-Christophe Deloulme and Gaëlle Dall'Igna and Nicolas Chauliac and Albane Pelluet and Anne-Sophie Nguon and Celia Lentini and Jacques Brocard and Eric Denarier and Sabine Brugière and Yohann Couté and Christophe Heinrich and Christophe Porcher and Jérôme Holtzmann and Annie Andrieux and Marie-Françoise Suaud-Chagny and Sylvie Gory-Fauré}, doi = {10.1016/j.brs.2018.08.001}, issn = {1876-4754}, year = {2018}, date = {2018-12-01}, journal = {Brain Stimulation}, volume = {11}, number = {6}, pages = {1336--1347}, abstract = {BACKGROUND: Severe and medication-resistant psychiatric diseases, such as major depressive disorder, bipolar disorder or schizophrenia, can be effectively and rapidly treated by electroconvulsive therapy (ECT). Despite extensive long-standing clinical use, the neurobiological mechanisms underlying the curative action of ECT remain incompletely understood. OBJECTIVE: Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT. METHODS: Using MAP6 KO mouse, a genetic model that constitutively exhibits features relevant to some aspects of depression; we analyzed the behavioral and biological consequences of ECS treatment alone (10 stimulations over a 2-week period) and associated with a continuation protocol (2 stimulations per week for 5 weeks). RESULTS: ECS treatment had a beneficial effect on constitutive behavioral defects. We showed that behavioral improvement is associated with a strong increase in the survival and integration of neurons born before ECS treatment. Retroviral infection revealed the larger number of integrated neurons to exhibit increased dendritic complexity and spine density, as well as remodeled synapses. Furthermore, our results show that ECS triggers a cortical increase in synaptogenesis. A sustained newborn neuron survival rate, induced by ECS treatment, is associated with the behavioral improvement, but relapse occurred 40 days after completing the ECS treatment. However, a 5-week continuation protocol following the initial ECS treatment led to persistent improvement of behavior correlated with sustained rate survival of newborn neurons. CONCLUSION: Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Severe and medication-resistant psychiatric diseases, such as major depressive disorder, bipolar disorder or schizophrenia, can be effectively and rapidly treated by electroconvulsive therapy (ECT). Despite extensive long-standing clinical use, the neurobiological mechanisms underlying the curative action of ECT remain incompletely understood. OBJECTIVE: Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT. METHODS: Using MAP6 KO mouse, a genetic model that constitutively exhibits features relevant to some aspects of depression; we analyzed the behavioral and biological consequences of ECS treatment alone (10 stimulations over a 2-week period) and associated with a continuation protocol (2 stimulations per week for 5 weeks). RESULTS: ECS treatment had a beneficial effect on constitutive behavioral defects. We showed that behavioral improvement is associated with a strong increase in the survival and integration of neurons born before ECS treatment. Retroviral infection revealed the larger number of integrated neurons to exhibit increased dendritic complexity and spine density, as well as remodeled synapses. Furthermore, our results show that ECS triggers a cortical increase in synaptogenesis. A sustained newborn neuron survival rate, induced by ECS treatment, is associated with the behavioral improvement, but relapse occurred 40 days after completing the ECS treatment. However, a 5-week continuation protocol following the initial ECS treatment led to persistent improvement of behavior correlated with sustained rate survival of newborn neurons. CONCLUSION: Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS. |
Albaret, Marie Alexandra; Vermot-Desroches, Claudine; Paré, Arnaud; Roca-Martinez, Jean-Xavier; Malet, Lucie; Esseily, Jad; Gerossier, Laetitia; Brière, Johan; Pion, Nathalie; Marcel, Virginie; Catez, Frédéric; Souza, Geneviève De; Vuillermoz, Boris; Doerflinger, Franck; Lavocat, Emilie; Subiger, Olivier; Rousset, Carine; Bresson, Corinne; Mandon, Elodie; Jawhari, Anass; Falson, Pierre; Jasmin, Mélissa; Couté, Yohann; Mertani, Hichem-Claude; Saintigny, Pierre; Diaz, Jean-Jacques Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells (Article de journal) Cancers, 10 (11), 2018, ISSN: 2072-6694. @article{albaret_externalized_2018, title = {Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells}, author = {Marie Alexandra Albaret and Claudine Vermot-Desroches and Arnaud Paré and Jean-Xavier Roca-Martinez and Lucie Malet and Jad Esseily and Laetitia Gerossier and Johan Brière and Nathalie Pion and Virginie Marcel and Frédéric Catez and Geneviève De Souza and Boris Vuillermoz and Franck Doerflinger and Emilie Lavocat and Olivier Subiger and Carine Rousset and Corinne Bresson and Elodie Mandon and Anass Jawhari and Pierre Falson and Mélissa Jasmin and Yohann Couté and Hichem-Claude Mertani and Pierre Saintigny and Jean-Jacques Diaz}, doi = {10.3390/cancers10110452}, issn = {2072-6694}, year = {2018}, date = {2018-11-01}, journal = {Cancers}, volume = {10}, number = {11}, abstract = {Accumulating evidence supports the remarkable presence at the membrane surface of cancer cells of proteins, which are normally expressed in the intracellular compartment. Although these proteins, referred to as externalized proteins, represent a highly promising source of accessible and druggable targets for cancer therapy, the mechanisms via which they impact cancer biology remain largely unexplored. The aim of this study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, we generated a unique antagonist monoclonal antibody (D-A10 MAb) targeting an eight-amino-acid-long domain of eK8, which enabled us to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC). We showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, we demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. We, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Accumulating evidence supports the remarkable presence at the membrane surface of cancer cells of proteins, which are normally expressed in the intracellular compartment. Although these proteins, referred to as externalized proteins, represent a highly promising source of accessible and druggable targets for cancer therapy, the mechanisms via which they impact cancer biology remain largely unexplored. The aim of this study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, we generated a unique antagonist monoclonal antibody (D-A10 MAb) targeting an eight-amino-acid-long domain of eK8, which enabled us to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC). We showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, we demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. We, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations. |
Hahn, Friedrich; Hutterer, Corina; Henry, Christophe; Hamilton, Stuart T; Strojan, Hanife; Kraut, Alexandra; Schulte, Ulrike; Schütz, Martin; Kohrt, Stephan; Wangen, Christina; Pfizer, José; Couté, Yohann; Rawlinson, William D; Strobl, Stefan; Marschall, Manfred Novel cytomegalovirus-inhibitory compounds of the class pyrrolopyridines show a complex pattern of target binding that suggests an unusual mechanism of antiviral activity (Article de journal) Antiviral Research, 159 , p. 84–94, 2018, ISSN: 1872-9096. @article{hahn_novel_2018, title = {Novel cytomegalovirus-inhibitory compounds of the class pyrrolopyridines show a complex pattern of target binding that suggests an unusual mechanism of antiviral activity}, author = {Friedrich Hahn and Corina Hutterer and Christophe Henry and Stuart T Hamilton and Hanife Strojan and Alexandra Kraut and Ulrike Schulte and Martin Schütz and Stephan Kohrt and Christina Wangen and José Pfizer and Yohann Couté and William D Rawlinson and Stefan Strobl and Manfred Marschall}, doi = {10.1016/j.antiviral.2018.09.012}, issn = {1872-9096}, year = {2018}, date = {2018-11-01}, journal = {Antiviral Research}, volume = {159}, pages = {84--94}, abstract = {Human cytomegalovirus (HCMV) is a major human pathogen with seropositivity rates in the adult population ranging between 40% and 95%. HCMV infection is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Current standard therapy with valganciclovir has the disadvantage of adverse side effects and viral drug resistance. A novel anti-HCMV drug, letermovir, has been approved recently, so that improved therapy options are available. Nevertheless, even more so far unexploited classes of compounds and molecular modes of action will be required for a next generation of antiherpesviral treatment strategies. In this study, we focused on the analysis of the antiviral potency of a novel class of compounds, i.e. pyrrolopyridine analogs, and identified both hit compounds and their target protein candidates. In essence, we provide novel evidence as follows: (i) screening hit SC88941 is highly active in inhibiting HCMV replication in primary human fibroblasts with an EC50 value of 0.20 ± 0.01 μM in the absence of cytotoxicity, (ii) inhibition occurs at the early-late stage of viral protein production and shows reinforcing effects upon LMV cotreatment, (iii) among the viruses analyzed, antiviral activity was most pronounced against β-herpesviruses (HCMV, HHV-6A) and intermediate against adenovirus (HAdV-2), (iv) induction of SC88941 resistance was not detectable, thus differed from the induction of ganciclovir resistance, (v) a linker-coupled model compound was used for mass spectrometry-based target identification, thus yielding several drug-binding target proteins and (vi) a first confocal imaging approach used for addressing intracellular effects of SC88941 indicated qualitative and quantitative alteration of viral protein expression and localization. Thus, our findings suggest a multifaceted pattern of compound-target binding in connection with an unusual mode of action, opening up further opportunities of antiviral drug development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Human cytomegalovirus (HCMV) is a major human pathogen with seropositivity rates in the adult population ranging between 40% and 95%. HCMV infection is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Current standard therapy with valganciclovir has the disadvantage of adverse side effects and viral drug resistance. A novel anti-HCMV drug, letermovir, has been approved recently, so that improved therapy options are available. Nevertheless, even more so far unexploited classes of compounds and molecular modes of action will be required for a next generation of antiherpesviral treatment strategies. In this study, we focused on the analysis of the antiviral potency of a novel class of compounds, i.e. pyrrolopyridine analogs, and identified both hit compounds and their target protein candidates. In essence, we provide novel evidence as follows: (i) screening hit SC88941 is highly active in inhibiting HCMV replication in primary human fibroblasts with an EC50 value of 0.20 ± 0.01 μM in the absence of cytotoxicity, (ii) inhibition occurs at the early-late stage of viral protein production and shows reinforcing effects upon LMV cotreatment, (iii) among the viruses analyzed, antiviral activity was most pronounced against β-herpesviruses (HCMV, HHV-6A) and intermediate against adenovirus (HAdV-2), (iv) induction of SC88941 resistance was not detectable, thus differed from the induction of ganciclovir resistance, (v) a linker-coupled model compound was used for mass spectrometry-based target identification, thus yielding several drug-binding target proteins and (vi) a first confocal imaging approach used for addressing intracellular effects of SC88941 indicated qualitative and quantitative alteration of viral protein expression and localization. Thus, our findings suggest a multifaceted pattern of compound-target binding in connection with an unusual mode of action, opening up further opportunities of antiviral drug development. |
Borges, Hélène; Guibert, Romain; Permiakova, Olga; Burger, Thomas Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra (Article de journal) Journal of Proteome Research, 2018, ISSN: 1535-3907. @article{borges_distinguishing_2018, title = {Distinguishing between Spectral Clustering and Cluster Analysis of Mass Spectra}, author = {Hélène Borges and Romain Guibert and Olga Permiakova and Thomas Burger}, doi = {10.1021/acs.jproteome.8b00516}, issn = {1535-3907}, year = {2018}, date = {2018-11-01}, journal = {Journal of Proteome Research}, abstract = {The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The term "spectral clustering" is sometimes used to refer to the clustering of mass spectrometry data. However, it also classically refers to a family of popular clustering algorithms. To avoid confusion, a more specific term could advantageously be coined. |
Dominguez-Medina, Sergio; Fostner, Shawn; Defoort, Martial; Sansa, Marc; Stark, Ann-Kathrin; Halim, Mohammad Abdul; Vernhes, Emeline; Gely, Marc; Jourdan, Guillaume; Alava, Thomas; Boulanger, Pascale; Masselon, Christophe; Hentz, Sébastien Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators (Article de journal) Science (New York, N.Y.), 362 (6417), p. 918–922, 2018, ISSN: 1095-9203. @article{dominguez-medina_neutral_2018, title = {Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators}, author = {Sergio Dominguez-Medina and Shawn Fostner and Martial Defoort and Marc Sansa and Ann-Kathrin Stark and Mohammad Abdul Halim and Emeline Vernhes and Marc Gely and Guillaume Jourdan and Thomas Alava and Pascale Boulanger and Christophe Masselon and Sébastien Hentz}, doi = {10.1126/science.aat6457}, issn = {1095-9203}, year = {2018}, date = {2018-11-01}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {918--922}, abstract = {Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of textasciitilde30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of textasciitilde30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100. |
Do, Le Duy; Gupton, Stéphanie L; Tanji, Kunikazu; Bastien, Joubert; Brugière, Sabine; Couté, Yohann; Quadrio, Isabelle; Rogemond, Véronique; Fabien, Nicole; Desestret, Virginie; Honnorat, Jérôme TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration (Article de journal) Cerebellum (London, England), 2018, ISSN: 1473-4230. @article{do_trim9_2018, title = {TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration}, author = {Le Duy Do and Stéphanie L Gupton and Kunikazu Tanji and Joubert Bastien and Sabine Brugière and Yohann Couté and Isabelle Quadrio and Véronique Rogemond and Nicole Fabien and Virginie Desestret and Jérôme Honnorat}, doi = {10.1007/s12311-018-0987-5}, issn = {1473-4230}, year = {2018}, date = {2018-10-01}, journal = {Cerebellum (London, England)}, abstract = {To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.}, keywords = {}, pubstate = {published}, tppubtype = {article} } To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected. |
Völz, Ronny; Kim, Soon-Kap; Mi, Jianing; Mariappan, Kiruthiga G; Guo, Xiujie; Bigeard, Jean; Alejandro, Santiago; Pflieger, Delphine; Rayapuram, Naganand; Al-Babili, Salim; Hirt, Heribert The Trihelix transcription factor GT2-like 1 (GTL1) promotes salicylic acid metabolism, and regulates bacterial-triggered immunity (Article de journal) PLoS genetics, 14 (10), p. e1007708, 2018, ISSN: 1553-7404. @article{volz_trihelix_2018, title = {The Trihelix transcription factor GT2-like 1 (GTL1) promotes salicylic acid metabolism, and regulates bacterial-triggered immunity}, author = {Ronny Völz and Soon-Kap Kim and Jianing Mi and Kiruthiga G Mariappan and Xiujie Guo and Jean Bigeard and Santiago Alejandro and Delphine Pflieger and Naganand Rayapuram and Salim Al-Babili and Heribert Hirt}, doi = {10.1371/journal.pgen.1007708}, issn = {1553-7404}, year = {2018}, date = {2018-10-01}, journal = {PLoS genetics}, volume = {14}, number = {10}, pages = {e1007708}, abstract = {The Trihelix Transcription factor GT2-like 1 (GTL1) was previously shown to be a key regulator of ploidy-dependent trichome growth and drought tolerance. Here, we report that GTL1 plays an important role in coordinating plant immunity. We show that gtl1 mutants are compromised in the regulation of basal immunity, microbial pattern-triggered immunity (PTI) and effector-triggered RIN4-mediated immunity. Transcriptome analysis revealed that GTL1 positively regulates defense genes and inhibits factors that mediate growth and development. By performing hormonal measurements and chromatin-immunoprecipitation studies, we found GTL1 to coordinate genes involved in salicylic acid metabolism, transport and response. Interaction studies and comparative transcriptomics to known data sets revealed that GTL1 is part of the MPK4 pathway and regulates oppositely the expression of differentially expressed genes in mpk4 plants. We introduced the gtl1 mutation in the mpk4 mutant and thereby partially suppressed its dwarfism and the high resistance against a bacterial invader. Our data show that GTL1 is part of the MPK4 pathway and acts as a positive regulator of bacterial-triggered immunity and SA homeostasis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Trihelix Transcription factor GT2-like 1 (GTL1) was previously shown to be a key regulator of ploidy-dependent trichome growth and drought tolerance. Here, we report that GTL1 plays an important role in coordinating plant immunity. We show that gtl1 mutants are compromised in the regulation of basal immunity, microbial pattern-triggered immunity (PTI) and effector-triggered RIN4-mediated immunity. Transcriptome analysis revealed that GTL1 positively regulates defense genes and inhibits factors that mediate growth and development. By performing hormonal measurements and chromatin-immunoprecipitation studies, we found GTL1 to coordinate genes involved in salicylic acid metabolism, transport and response. Interaction studies and comparative transcriptomics to known data sets revealed that GTL1 is part of the MPK4 pathway and regulates oppositely the expression of differentially expressed genes in mpk4 plants. We introduced the gtl1 mutation in the mpk4 mutant and thereby partially suppressed its dwarfism and the high resistance against a bacterial invader. Our data show that GTL1 is part of the MPK4 pathway and acts as a positive regulator of bacterial-triggered immunity and SA homeostasis. |
Gervais, Virginie; Mari, Isabelle Muller Pierre-Olivier; Mourcet, Amandine; Movellan, Kumar Tekwani; Ramos, Pascal; Marcoux, Julien; Guillet, Valérie; Javaid, Sumaira; Burlet-Schiltz, Odile; Czaplicki, Georges; Milon, Alain; Giglia-Mari, Giuseppina Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy (Article de journal) J Biol Chem., 293 (39), p. 14974-14988, 2018. @article{Gervais2018, title = {Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy}, author = {Virginie Gervais and Isabelle Muller Pierre-Olivier Mari and Amandine Mourcet and Kumar Tekwani Movellan and Pascal Ramos and Julien Marcoux and Valérie Guillet and Sumaira Javaid and Odile Burlet-Schiltz and Georges Czaplicki and Alain Milon and Giuseppina Giglia-Mari}, doi = {10.1074/jbc.RA118.003444}, year = {2018}, date = {2018-09-28}, journal = {J Biol Chem.}, volume = {293}, number = {39}, pages = {14974-14988}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Shiota, Hitoshi; Barral, Sophie; Buchou, Thierry; Tan, Minjia; Couté, Yohann; Charbonnier, Guillaume; Reynoird, Nicolas; Boussouar, Fayçal; Gérard, Matthieu; Zhu, Mingrui; Bargier, Lisa; Puthier, Denis; Chuffart, Florent; Bourova-Flin, Ekaterina; Picaud, Sarah; Filippakopoulos, Panagis; Goudarzi, Afsaneh; Ibrahim, Ziad; Panne, Daniel; Rousseaux, Sophie; Zhao, Yingming; Khochbin, Saadi Nut Directs p300-Dependent, Genome-Wide Ħ4 Hyperacetylation in Male Germ Cells (Article de journal) Cell Reports, 24 (13), p. 3477–3487.e6, 2018, ISSN: 2211-1247. @article{shiota_nut_2018, title = {Nut Directs p300-Dependent, Genome-Wide Ħ4 Hyperacetylation in Male Germ Cells}, author = {Hitoshi Shiota and Sophie Barral and Thierry Buchou and Minjia Tan and Yohann Couté and Guillaume Charbonnier and Nicolas Reynoird and Fayçal Boussouar and Matthieu Gérard and Mingrui Zhu and Lisa Bargier and Denis Puthier and Florent Chuffart and Ekaterina Bourova-Flin and Sarah Picaud and Panagis Filippakopoulos and Afsaneh Goudarzi and Ziad Ibrahim and Daniel Panne and Sophie Rousseaux and Yingming Zhao and Saadi Khochbin}, doi = {10.1016/j.celrep.2018.08.069}, issn = {2211-1247}, year = {2018}, date = {2018-09-01}, journal = {Cell Reports}, volume = {24}, number = {13}, pages = {3477--3487.e6}, abstract = {Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. |
Nguyen, Minh Vu Chuong; Adrait, Annie; Baillet, Athan; Trocmé, Candice; Gottenberg, Jacques-Eric; Gaudin, Philippe Identification of cartilage oligomeric matrix protein as biomarker predicting abatacept response in rheumatoid arthritis patients with insufficient response to a first anti-TNFα treatment (Article de journal) Joint, Bone, Spine: Revue Du Rhumatisme, 2018, ISSN: 1778-7254. @article{nguyen_identification_2018, title = {Identification of cartilage oligomeric matrix protein as biomarker predicting abatacept response in rheumatoid arthritis patients with insufficient response to a first anti-TNFα treatment}, author = {Minh Vu Chuong Nguyen and Annie Adrait and Athan Baillet and Candice Trocmé and Jacques-Eric Gottenberg and Philippe Gaudin}, doi = {10.1016/j.jbspin.2018.09.005}, issn = {1778-7254}, year = {2018}, date = {2018-09-01}, journal = {Joint, Bone, Spine: Revue Du Rhumatisme}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Mato, José M; Elortza, Félix; Lu, Shelly C; Brun, Virginie; Paradela, Alberto; Corrales, Fernando J Liver cancer-associated changes to the proteome: what deserves clinical focus? (Article de journal) Expert Review of Proteomics, 15 (9), p. 749–756, 2018, ISSN: 1744-8387. @article{mato_liver_2018, title = {Liver cancer-associated changes to the proteome: what deserves clinical focus?}, author = {José M Mato and Félix Elortza and Shelly C Lu and Virginie Brun and Alberto Paradela and Fernando J Corrales}, doi = {10.1080/14789450.2018.1521277}, issn = {1744-8387}, year = {2018}, date = {2018-09-01}, journal = {Expert Review of Proteomics}, volume = {15}, number = {9}, pages = {749--756}, abstract = {INTRODUCTION: Hepatocellular carcinoma (HCC) is recognized as the fifth most common neoplasm and currently represents the second leading form of cancer-related death worldwide. Despite great progress has been done in the understanding of its pathogenesis, HCC represents a heavy societal and economic burden as most patients are still diagnosed at advanced stages and the 5-year survival rate remain below 20%. Early detection and revolutionary therapies that rely on the discovery of new molecular biomarkers and therapeutic targets are therefore urgently needed to develop precision medicine strategies for a more efficient management of patients. Areas covered: This review intends to comprehensively analyse the proteomics-based research conducted in the last few years to address some of the principal still open riddles in HCC biology, based on the identification of molecular drivers of tumor progression and metastasis. Expert commentary: The technical advances in mass spectrometry experienced in the last decade have significantly improved the analytical capacity of proteome wide studies. Large-scale protein and protein variant (post-translational modifications) identification and quantification have allowed detailed dissections of molecular mechanisms underlying HCC progression and are already paving the way for the identification of clinically relevant proteins and the development of their use on patient care.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: Hepatocellular carcinoma (HCC) is recognized as the fifth most common neoplasm and currently represents the second leading form of cancer-related death worldwide. Despite great progress has been done in the understanding of its pathogenesis, HCC represents a heavy societal and economic burden as most patients are still diagnosed at advanced stages and the 5-year survival rate remain below 20%. Early detection and revolutionary therapies that rely on the discovery of new molecular biomarkers and therapeutic targets are therefore urgently needed to develop precision medicine strategies for a more efficient management of patients. Areas covered: This review intends to comprehensively analyse the proteomics-based research conducted in the last few years to address some of the principal still open riddles in HCC biology, based on the identification of molecular drivers of tumor progression and metastasis. Expert commentary: The technical advances in mass spectrometry experienced in the last decade have significantly improved the analytical capacity of proteome wide studies. Large-scale protein and protein variant (post-translational modifications) identification and quantification have allowed detailed dissections of molecular mechanisms underlying HCC progression and are already paving the way for the identification of clinically relevant proteins and the development of their use on patient care. |
Locard-Paulet, Marie; Parra, Julien; Albigot, Renaud; Mouton-Barbosa, Emmanuelle; Bardi, Laurent; Burlet-Schiltz, Odile; Marcoux, Julien VisioProt-MS: interactive 2D maps from intact protein mass spectrometry (Article de journal) Bioinformatics, 2018. @article{Locard-Paulet2018, title = {VisioProt-MS: interactive 2D maps from intact protein mass spectrometry}, author = {Marie Locard-Paulet and Julien Parra and Renaud Albigot and Emmanuelle Mouton-Barbosa and Laurent Bardi and Odile Burlet-Schiltz and Julien Marcoux}, doi = {10.1093/bioinformatics/bty680}, year = {2018}, date = {2018-08-06}, journal = {Bioinformatics}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Vinel, Claire; Lukjanenko, Laura; Batut, Aurélie; Deleruyelle, Simon; Pradère, Jean-Philippe; Gonidec, Sophie Le; Dortignac, Alizée; Geoffre, Nancy; Pereira, Ophélie; Karaz, Sonia; Lee, Umji; Camus, Mylène; Chaoui, Karima; Mouisel, Etienne; Bigot, Anne; Mouly, Vincent; Vigneau, Mathieu; Pagano, Allan F; Chopard, Angèle; Pillard, Fabien; Guyonnet, Sophie; Cesari, Matteo; Burlet-Schiltz, Odile; Pahor, Marco; Feige, Jérôme N; Vellas, Bruno; Valet, Philippe; Dray, Cédric The exerkine apelin reverses age-associated sarcopenia (Article de journal) Nat Med., 24 (9), p. 1360-71, 2018. @article{Vinel2018, title = {The exerkine apelin reverses age-associated sarcopenia}, author = {Claire Vinel and Laura Lukjanenko and Aurélie Batut and Simon Deleruyelle and Jean-Philippe Pradère and Sophie Le Gonidec and Alizée Dortignac and Nancy Geoffre and Ophélie Pereira and Sonia Karaz and Umji Lee and Mylène Camus and Karima Chaoui and Etienne Mouisel and Anne Bigot and Vincent Mouly and Mathieu Vigneau and Allan F. Pagano and Angèle Chopard and Fabien Pillard and Sophie Guyonnet and Matteo Cesari and Odile Burlet-Schiltz and Marco Pahor and Jérôme N. Feige and Bruno Vellas and Philippe Valet and Cédric Dray}, doi = {10.1038/s41591-018-0131-6}, year = {2018}, date = {2018-07-30}, journal = {Nat Med.}, volume = {24}, number = {9}, pages = {1360-71}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Jonik-Nowak, Beata; Menneteau, Thoma; Fesquet, Didier; Baldin, Véronique; Bonne-Andrea, Catherine; Méchali, Francisca; Fabre, Bertrand; Boisguerin, Prisca; de Rossi, Sylvain; Henriquet, Corinne; Pugnière, Martine; Ducoux-Petit, Manuelle; Burlet-Schiltz, Odile; Lamond, Angus I; Fort, Philippe; Boulon, Séverine; Bousquet, Mari-Pierre; Coux, Olivier PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ (Article de journal) Proc Natl Acad Sci U S A., 115 (28), p. E6477-E6486, 2018. @article{Jonik-Nowak2018, title = {PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ}, author = {Beata Jonik-Nowak and Thoma Menneteau and Didier Fesquet and Véronique Baldin and Catherine Bonne-Andrea and Francisca Méchali and Bertrand Fabre and Prisca Boisguerin and Sylvain de Rossi and Corinne Henriquet and Martine Pugnière and Manuelle Ducoux-Petit and Odile Burlet-Schiltz and Angus I. Lamond and Philippe Fort and Séverine Boulon and Mari-Pierre Bousquet and Olivier Coux}, doi = {10.1073/pnas.1722299115}, year = {2018}, date = {2018-07-10}, journal = {Proc Natl Acad Sci U S A.}, volume = {115}, number = {28}, pages = {E6477-E6486}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Gaud, Guillaume; Roncagalli, Romain; Chaoui, Karima; Bernard, Isabelle; andCéline Colacios, Julien Familiades; Kassem, Sahar; Monsarrat, Bernard; Burlet-Schiltz, Odile; de Peredo, Anne Gonzalez; Malissen, Bernard; Saoudi, Abdelhadi The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells (Article de journal) 11 (538), p. eaar3083, 2018. @article{Gaud2018, title = {The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells}, author = {Guillaume Gaud and Romain Roncagalli and Karima Chaoui and Isabelle Bernard and Julien Familiades andCéline Colacios and Sahar Kassem and Bernard Monsarrat and Odile Burlet-Schiltz and Anne Gonzalez de Peredo and Bernard Malissen and Abdelhadi Saoudi}, doi = {10.1126/scisignal.aar3083}, year = {2018}, date = {2018-07-10}, volume = {11}, number = {538}, pages = {eaar3083}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Behrens, Christina; Biela, Inna; andThomas Botzanowski, Stéphanie Petiot-Bécard; Cianférani, Sarah; Sager, Christoph P; Klebe, Gerhard; Heine, Andreas; Reuter, Klaus Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase (Article de journal) Biochemistry, 57 (26), p. 3953–3965, 2018. @article{Behrens2018, title = {Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase}, author = {Christina Behrens and Inna Biela and Stéphanie Petiot-Bécard andThomas Botzanowski and Sarah Cianférani and Christoph P. Sager and Gerhard Klebe and Andreas Heine and Klaus Reuter}, doi = {10.1021/acs.biochem.8b00294}, year = {2018}, date = {2018-06-04}, journal = {Biochemistry}, volume = {57}, number = {26}, pages = {3953–3965}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fröhlich, Tony; Hahn, Friedrich; Belmudes, Lucid; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Couté, Yohann; Marschall, Manfred; Tsogoeva, Svetlana B Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action (Article de journal) Chemistry (Weinheim an Der Bergstrasse, Germany), 24 (32), p. 8103–8113, 2018, ISSN: 1521-3765. @article{frohlich_synthesis_2018, title = {Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action}, author = {Tony Fröhlich and Friedrich Hahn and Lucid Belmudes and Maria Leidenberger and Oliver Friedrich and Barbara Kappes and Yohann Couté and Manfred Marschall and Svetlana B Tsogoeva}, doi = {10.1002/chem.201800729}, issn = {1521-3765}, year = {2018}, date = {2018-06-01}, journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)}, volume = {24}, number = {32}, pages = {8103--8113}, abstract = {Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 μm) and artesunic acid (EC50 5.41 μm). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 μm, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 μm) and artesunic acid (EC50 5.41 μm). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified. |
Jacob, Laurent; Combes, Florence; Burger, Thomas PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides (Article de journal) Biostatistics (Oxford, England), 2018, ISSN: 1468-4357. @article{jacob_pepa_2018, title = {PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides}, author = {Laurent Jacob and Florence Combes and Thomas Burger}, doi = {10.1093/biostatistics/kxy021}, issn = {1468-4357}, year = {2018}, date = {2018-06-01}, journal = {Biostatistics (Oxford, England)}, abstract = {We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via the pepa.test function of the DAPAR Bioconductor R package.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via the pepa.test function of the DAPAR Bioconductor R package. |
Denadai-Souza, Alexandre; Bonnart, Chrystelle; Tapias, Núria Solà; Marcellin, Marlène; andLaurent Alric, Brendan Gilmore; Bonnet, Delphine; Burlet-Schiltz, Odile; Hollenberg, Morley D; Vergnolle, Nathalie; Deraison, Céline Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease (Article de journal) Sci Rep, 8 (1), p. 7834, 2018. @article{Denadai-Souza2018, title = {Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease}, author = {Alexandre Denadai-Souza and Chrystelle Bonnart and Núria Solà Tapias and Marlène Marcellin and Brendan Gilmore andLaurent Alric and Delphine Bonnet and Odile Burlet-Schiltz and Morley D. Hollenberg and Nathalie Vergnolle and Céline Deraison}, doi = {10.1038/s41598-018-26282-y}, year = {2018}, date = {2018-05-18}, journal = {Sci Rep}, volume = {8}, number = {1}, pages = {7834}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Lefebvre, Cyril; Boulon, Richard; Ducoux, Manuelle; Gavalda, Sabine; Laval, Françoise; Jamet, Stevie; Eynard, Nathalie; Lemassu, Anne; Cam, Kaymeuang; Bousquet, Marie-Pierre; Bardou, Fabienne; Burlet-Schiltz, Odile; Daffé, Mamadou; Quémard, Annaïck HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness (Article de journal) Sci Rep, 8 (1), p. 6034, 2018. @article{Lefebvre2018, title = {HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness}, author = {Cyril Lefebvre and Richard Boulon and Manuelle Ducoux and Sabine Gavalda and Françoise Laval and Stevie Jamet and Nathalie Eynard and Anne Lemassu and Kaymeuang Cam and Marie-Pierre Bousquet and Fabienne Bardou and Odile Burlet-Schiltz and Mamadou Daffé and Annaïck Quémard}, doi = {10.1038/s41598-018-24380-5}, year = {2018}, date = {2018-04-16}, journal = {Sci Rep}, volume = {8}, number = {1}, pages = {6034}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
