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2. Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma

Author

El-Hachem, Najla, Leclercq, Marine, Susaeta Ruiz, Miguel, Vanleyssem, Raphael, Shostak, Kateryna, Körner, Pierre-René, Capron, Coralie, Martin-Morales, Lorena, Roncarati, Patrick, Lavergne, Arnaud, Blomme, Arnaud, Turchetto, Silvia, Goffin, Eric, Thandapani, Palaniraja, Tarassov, Ivan, Nguyen, Laurent, Pirotte, Bernard, Chariot, Alain, Marine, Jean-Christophe, Herfs, Michael, Rapino, Francesca, Agami, Reuven, and Close, Pierre

Published
2024
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3. Hot Rolling Modelling: Optimization of Trimmed Area Based on Crocodiling and Edge Cracking Simulations

Author

Nguyen, Laurent, Barthelemy, Alexandre, Harrup, Anthony, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Mocellin, Katia, editor, Bouchard, Pierre-Olivier, editor, Bigot, Régis, editor, and Balan, Tudor, editor

Published
2024
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4. Author Correction: CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

Author

de Thonel, Aurélie, Ahlskog, Johanna K., Daupin, Kevin, Dubreuil, Véronique, Berthelet, Jérémy, Chaput, Carole, Pires, Geoffrey, Leonetti, Camille, Abane, Ryma, Barris, Lluís Cordón, Leray, Isabelle, Aalto, Anna L., Naceri, Sarah, Cordonnier, Marine, Benasolo, Carène, Sanial, Matthieu, Duchateau, Agathe, Vihervaara, Anniina, Puustinen, Mikael C., Miozzo, Federico, Fergelot, Patricia, Lebigot, Élise, Verloes, Alain, Gressens, Pierre, Lacombe, Didier, Gobbo, Jessica, Garrido, Carmen, Westerheide, Sandy D., David, Laurent, Petitjean, Michel, Taboureau, Olivier, Rodrigues-Lima, Fernando, Passemard, Sandrine, Sabéran-Djoneidi, Délara, Nguyen, Laurent, Lancaster, Madeline, Sistonen, Lea, and Mezger, Valérie

Published
2023
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10. Building Bridges Between the Clinic and the Laboratory: A Meeting Review – Brain Malformations: A Roadmap for Future Research

Author

Sapir, Tamar, Barakat, Tahsin Stefan, Paredes, Mercedes F, Lerman-Sagie, Tally, Aronica, Eleonora, Klonowski, Wlodzimierz, Nguyen, Laurent, Zeev, Bruria Ben, Bahi-Buisson, Nadia, Leventer, Richard, Rachmian, Noa, and Reiner, Orly

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Psychology, Neurosciences, Brain Disorders, brain malformations, brain development, neuronal migration, neuronal progenitors, brain organoids, mouse models, mTOR, brain plasticity, Biochemistry and Cell Biology, Biochemistry and cell biology, Biological psychology
Abstract

In the middle of March 2019, a group of scientists and clinicians (as well as those who wear both hats) gathered in the green campus of the Weizmann Institute of Science to share recent scientific findings, to establish collaborations, and to discuss future directions for better diagnosis, etiology modeling and treatment of brain malformations. One hundred fifty scientists from twenty-two countries took part in this meeting. Thirty-eight talks were presented and as many as twenty-five posters were displayed. This review is aimed at presenting some of the highlights that the audience was exposed to during the three-day meeting.

Published
2019

11. CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

Author

de Thonel, Aurélie, Ahlskog, Johanna K., Daupin, Kevin, Dubreuil, Véronique, Berthelet, Jérémy, Chaput, Carole, Pires, Geoffrey, Leonetti, Camille, Abane, Ryma, Barris, Lluís Cordón, Leray, Isabelle, Aalto, Anna L., Naceri, Sarah, Cordonnier, Marine, Benasolo, Carène, Sanial, Matthieu, Duchateau, Agathe, Vihervaara, Anniina, Puustinen, Mikael C., Miozzo, Federico, Fergelot, Patricia, Lebigot, Élise, Verloes, Alain, Gressens, Pierre, Lacombe, Didier, Gobbo, Jessica, Garrido, Carmen, Westerheide, Sandy D., David, Laurent, Petitjean, Michel, Taboureau, Olivier, Rodrigues-Lima, Fernando, Passemard, Sandrine, Sabéran-Djoneidi, Délara, Nguyen, Laurent, Lancaster, Madeline, Sistonen, Lea, and Mezger, Valérie

Published
2022
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17. ATP-citrate lyase promotes axonal transport across species

Author

Even, Aviel, Morelli, Giovanni, Turchetto, Silvia, Shilian, Michal, Bail, Romain Le, Laguesse, Sophie, Krusy, Nathalie, Brisker, Ariel, Brandis, Alexander, Inbar, Shani, Chariot, Alain, Saudou, Frédéric, Dietrich, Paula, Dragatsis, Ioannis, Brone, Bert, Broix, Loïc, Rigo, Jean-Michel, Weil, Miguel, and Nguyen, Laurent

Published
2021
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19. Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains

Author

Aubry, Fabien, Jacobs, Sofie, Darmuzey, Maïlis, Lequime, Sebastian, Delang, Leen, Fontaine, Albin, Jupatanakul, Natapong, Miot, Elliott F., Dabo, Stéphanie, Manet, Caroline, Montagutelli, Xavier, Baidaliuk, Artem, Gámbaro, Fabiana, Simon-Lorière, Etienne, Gilsoul, Maxime, Romero-Vivas, Claudia M., Cao-Lormeau, Van-Mai, Jarman, Richard G., Diagne, Cheikh T., Faye, Oumar, Faye, Ousmane, Sall, Amadou A., Neyts, Johan, Nguyen, Laurent, Kaptein, Suzanne J. F., and Lambrechts, Louis

Published
2021
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21. Prediction of CYP Down Regulation after Tusamitamab Ravtansine Administration (a DM4‐Conjugate), Based on an In Vitro–In Vivo Extrapolation Approach.

Author

Pouzin, Clemence, Teutonico, Donato, Fagniez, Nathalie, Ziti‐Ljajic, Samira, Perreard‐Dumaine, Anne, Pardon, Magalie, Klieber, Sylvie, and Nguyen, Laurent

Subjects
CYTOCHROME P-450, EXTRAPOLATION, ANTIBODY-drug conjugates, CYTOCHROME P-450 CYP3A, DRUG interactions, TUBULINS, CYTOCHROME c
Abstract

Tusamitamab ravtansine is an antibody‐drug conjugate (ADC) composed of a humanized monoclonal antibody (IgG1) and DM4 payload. Even if DM4 and its main metabolite methyl‐DM4 (Me‐DM4) circulate at low concentrations after ADC administration, their potential as perpetrators of cytochrome P450 mediated drug–drug interaction was assessed. In vitro studies in human hepatocytes indicated that Me‐DM4 elicited a clear concentration‐dependent down regulation of cytochrome P450 enzymes (CYP3A4, 1A2, and 2B6). Because DM4 was unstable under the incubation conditions studied, the in vitro constants could not be determined for this entity. Thus, to predict the clinical relevance of this observed downregulation, an in vitro‐in vivo extrapolation (IVIVE) pharmacokinetic (PK) based approach was developed. To mitigate model prediction errors and because of their similar inhibitory effect on tubulin polymerization, the same downregulation constants were used for DM4 and Me‐DM4. This approach describes the time course of decreasing CYP3A4, 1A2, and 2B6 enzyme amounts as a function of circulating concentrations of DM4 and Me‐DM4 predicted from a population PK model. The developed IVIVE‐PK model showed that the highest CYP abundance decrease was observed for CYP3A4, with a transient reduction of < 10% from baseline. The impact on midazolam exposure, as probe substrate of CYP3A, was then simulated based on a physiologically‐based PK static method. The maximal CYP3A4 abundance reduction was associated with a predicted midazolam area under the curve (AUC) ratio of 1.14. To conclude, the observed in vitro downregulation of CYPs by Me‐DM4 is not expected to have relevant clinical impact. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Characteristics of severe asthma patients included in the French Palomb Cohort.

Author

Jestin-Guyon, Nolwenn, primary, Ouaalaya, El Hassane, additional, Ozier, Annaig, additional, Nocent, Cécilia, additional, Bernady, Alain, additional, Nguyen, Laurent, additional, Berteaud, Emilie, additional, Dupuy-Grasset, Magali, additional, Le Guillou, Frédéric, additional, Melloni, Boris, additional, Portel, Laurent, additional, Prud’Homme, Anne, additional, Didier, Alain, additional, Molimard, Mathieu, additional, Guilleminault, Laurent, additional, and Raherison-Semjen, Chantal, additional

Published
2023
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23. Sex differences in mortality among COPD patients: the French Palomb Cohort.

Author

Jestin-Guyon, Nolwenn, primary, Ouaalaya, El Hassane, additional, Falque, Laurent, additional, Nguyen, Laurent, additional, Ozier, Annaig, additional, Bernady, Alain, additional, Berteaud, Emilie, additional, Casteigt, Julien, additional, Le Guillou, Frédéric, additional, Moinard, Jean, additional, Staali, Mohamed, additional, Nocent, Cécilia, additional, Molimard, Mathieu, additional, and Raherison-Semjen, Chantal, additional

Published
2023
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27. Contributors

Author

Beaubien, François, primary, Bielle, Franck, additional, Bradke, Frank, additional, Charron, Frédéric, additional, Chédotal, Alain, additional, Cloutier, Jean-François, additional, Cunningham, Christopher L., additional, de Castro, Fernando, additional, Flynn, Kevin C., additional, García-Moreno, Fernando, additional, Garel, Sonia, additional, Giger, R.J., additional, Grueber, Wesley B., additional, Hayashi, K., additional, He, Zhigang, additional, Higginbotham, Holden, additional, Iversen, Katrine, additional, Kania, Artur, additional, Karzbrun, Eyal, additional, Kriegstein, Arnold R., additional, Krsnik, Zeljka, additional, Laumonnerie, Christophe, additional, Lefebvre, Julie L., additional, Lepiemme, Fanny, additional, Li, Guangnan, additional, LoTurco, Joseph J., additional, Ma, Le, additional, Manent, Jean-Bernard, additional, Marocha, Julie, additional, Molnár, Zoltán, additional, Nakajima, K., additional, Nguyen, Laurent, additional, Noctor, Stephen C., additional, Noguchi, Hirofumi, additional, Pasterkamp, R. Jeroen, additional, Pleasure, Samuel J., additional, Polleux, F., additional, Popovitchenko, Tatiana, additional, Prince, Janet E.A., additional, Rasin, Mladen-Roko, additional, Reiner, Orly, additional, Sawada, Masato, additional, Sawamoto, Kazunobu, additional, Sekine, K., additional, Silva G., Carla, additional, Solecki, David J., additional, Sotelo, Constantino, additional, Tabata, H., additional, Tessier-Lavigne, Marc, additional, Tymanskyj, Stephen R., additional, Verhagen, Marieke G., additional, Wang, Fan, additional, Weth, Franco, additional, Yam, Patricia T., additional, Yang, Jing, additional, Ye, Bing, additional, and Zalc, Bernard, additional

Published
2020
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29. The centrosome protein AKNA regulates neurogenesis via microtubule organization

Author

Camargo Ortega, Germán, Falk, Sven, Johansson, Pia A., Peyre, Elise, Broix, Loïc, Sahu, Sanjeeb Kumar, Hirst, William, Schlichthaerle, Thomas, De Juan Romero, Camino, Draganova, Kalina, Vinopal, Stanislav, Chinnappa, Kaviya, Gavranovic, Anna, Karakaya, Tugay, Steininger, Thomas, Merl-Pham, Juliane, Feederle, Regina, Shao, Wei, Shi, Song-Hai, Hauck, Stefanie M., Jungmann, Ralf, Bradke, Frank, Borrell, Victor, Geerlof, Arie, Reber, Simone, Tiwari, Vijay K., Huttner, Wieland B., Wilsch-Bräuninger, Michaela, Nguyen, Laurent, and Götz, Magdalena

Published
2019
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33. Supplementary figures 1-3 from Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Author

Tierny, Dominique, primary, Serres, François, primary, Segaoula, Zacharie, primary, Bemelmans, Ingrid, primary, Bouchaert, Emmanuel, primary, Pétain, Aurélie, primary, Brel, Viviane, primary, Couffin, Stéphane, primary, Marchal, Thierry, primary, Nguyen, Laurent, primary, Thuru, Xavier, primary, Ferré, Pierre, primary, Guilbaud, Nicolas, primary, and Gomes, Bruno, primary

Published
2023
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34. SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes

Author

Smits, Daphne J, primary, Schot, Rachel, additional, Krusy, Nathalie, additional, Wiegmann, Katja, additional, Utermöhlen, Olaf, additional, Mulder, Monique T, additional, den Hoedt, Sandra, additional, Yoon, Grace, additional, Deshwar, Ashish R, additional, Kresge, Christina, additional, Pletcher, Beth, additional, van Mook, Maura, additional, Ferreira, Marta Serio, additional, Poot, Raymond A, additional, Slotman, Johan A, additional, Kremers, Gert-Jan, additional, Ahmad, Abeer, additional, Albash, Buthaina, additional, Bastaki, Laila, additional, Marafi, Dana, additional, Dekker, Jordy, additional, van Ham, Tjakko J, additional, Nguyen, Laurent, additional, and Mancini, Grazia M S, additional

Published
2023
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35. SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes

Author

Smits, Daphne J., Schot, Rachel, Krusy, Nathalie, Wiegmann, Katja, Utermöhlen, Olaf, Mulder, Monique T., den Hoedt, Sandra, Yoon, Grace, Deshwar, Ashish R., Kresge, Christina, Pletcher, Beth, van Mook, Maura, Ferreira, Marta Serio, Poot, Raymond A., Slotman, Johan A., Kremers, Gert Jan, Ahmad, Abeer, Albash, Buthaina, Bastaki, Laila, Marafi, Dana, Dekker, Jordy, van Ham, Tjakko J., Nguyen, Laurent, Mancini, Grazia M.S., Smits, Daphne J., Schot, Rachel, Krusy, Nathalie, Wiegmann, Katja, Utermöhlen, Olaf, Mulder, Monique T., den Hoedt, Sandra, Yoon, Grace, Deshwar, Ashish R., Kresge, Christina, Pletcher, Beth, van Mook, Maura, Ferreira, Marta Serio, Poot, Raymond A., Slotman, Johan A., Kremers, Gert Jan, Ahmad, Abeer, Albash, Buthaina, Bastaki, Laila, Marafi, Dana, Dekker, Jordy, van Ham, Tjakko J., Nguyen, Laurent, and Mancini, Grazia M.S.

Abstract

Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.

Published
2023

36. Elongator promotes neuritogenesis via regulation of tau stability through acly activity

Author

Shilian, Michal, Even, Aviel, Gast, Hila, Nguyen, Laurent, Weil, Miguel, Shilian, Michal, Even, Aviel, Gast, Hila, Nguyen, Laurent, and Weil, Miguel

Subjects
familial dysautonomia, neuritogenesis, protein acetylation, Cell Biology, MAPT/Tau protein, elongator complex, Developmental Biology
Abstract

The six subunits (Elp1 to Elp6) Elongator complex promotes specific uridine modifications in tRNA's wobble site. Moreover, this complex has been indirectly involved in the regulation of alpha-tubulin acetylation in microtubules (MTs) via the stabilization of ATP-Citrate Lyase (Acly), the main cytosolic source of acetyl-CoA production in cells, a key substrate used for global protein acetylation. Here, we report additional evidence that Elongator activity is important for proper cytoskeleton remodeling as cells lacking expression of Elp1 show morphology impairment; including distinct neurite process formation and disorganization and instability of MTs. Here, we show that loss of Elongator results in a reduction of expression of the microtubule associated protein Tau (MAPT). Tau, is a well-known key MT regulator in neurons whose lysines can be competitively acetylated or ubiquitylated. Therefore, we tested whether Tau is an indirect acetylation target of Elongator. We found that a reduction of Elongator activity leads to a decrease of lysine acetylation on Tau that favors its proteasomal degradation. This phenotype was prevented by using selective deacetylase or proteasomal inhibitors. Moreover, our data demonstrate that Acly's activity regulates the mechanism underlying Tau mediated neurite morphology defects found in Elp1 KD since both Tau levels and neurites morphology are restored due to Acly overexpression. This suggests a possible involvement of both Tau and Acly dysfunction in Familial Dysautonomia (FD), which is an autosomal recessive peripheral neuropathy caused by mutation in the ELP1 gene that severely affects Elp1 expression levels in the nervous system in FD patients in a similar way as found previously in Elp1 KD neuroblastoma cells. This work is supported by the Israel Science Foundation, ISF Grant No. 1688/16 and ISF Grant No. 1513/20. LN. is Research Director of the F.R.S- F.N.R.S. The work performed in the Nguyen laboratory is supported by ULiège (Crédit Classique), the F.R.S.-F.N.R.S. (PDR T.0185.20; EOS 0019118F-RG36), WELBIO (CR-2022A-12), the Fonds Leon Fredericq, the Fondation Médicale Reine Elisabeth, the Fondation Simone et Pierre Clerdent, the Belgian Science Policy (IAP-VII network P7/20), the ERANET Neuron (STEM-MCD and NeuroTalk), and the Win2Wal (ChipOmics; #2010126).

Published
2022

39. KIF2A deficiency causes early-onset neurodegeneration

Author

Ruiz-Reig, Nuria, primary, Chehade, Georges, additional, Hakanen, Janne, additional, Aittaleb, Mohamed, additional, Wierda, Keimpe, additional, De Wit, Joris, additional, Nguyen, Laurent, additional, Gailly, Philippe, additional, and Tissir, Fadel, additional

Published
2022
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41. E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE PROTEIN TRANSLATION FIDELITY DURING NEURONAL DEVELOPMENT

Author

Di Michele Michela, Attina Aurore, Laguesse Sophie, De Blasio Carlo, Wendling Olivia, Frenois Francois-Xavier, Encislai Betty, Fuentes Maryse, Jahanault-Tagliani Céline, Rousseau Mélanie, Roux Pierre-François, Guégan Justine, Buscail Yoan, Dupré Pierrick, Michaud Henri-Alexandre, Rodier Geneviève, Bellvert Floriant, Kulyk Barbier Hannah, Ferraro Peyret Carole, Mathieu Hugo, Chaveroux Cédric, Pirot Nelly, Rubio Lucie, Torro Adeline, Compan Vincent, Sorg Tania, Ango Fabrice, David Alexandre, Lebigot Elise, Legati Andrea, Hirtz Christophe, Ghezzi Daniele, Nguyen Laurent, Sardet Claude, Lacroix Matthieu, and Le Cam Laurent

Abstract

SUMMARYThe Leigh syndrome is a severe inborn neurodegenerative encephalopathy commonly associated with pyruvate metabolism defects. The transcription factor E4F1, a key regulator of the pyruvate dehydrogenase (PDH) complex (PDC), was previously found to be mutated in Leigh syndrome patients, but the molecular mechanisms leading to cell death in E4F1-deficient neurons remain unknown. Here, we show that E4F1 directly regulatesDlatandElp3, two genes encoding key subunits of the PDC and of the Elongator complex, to coordinate AcetylCoenzyme A production and its utilization to acetylate tRNAs. Genetic inactivation ofE4f1in neurons during mouse embryonic development impaired tRNAs editing and induced an ATF4-mediated integrated stress response (ISR), leading to neuronal cell death and microcephaly. Furthermore, our analysis of PDH-deficient cells unraveled a crosstalk linking the PDC to ELP3 expression that is perturbed in Leigh syndrome patients. Altogether, our data support a model where pyruvate metabolism regulates the epitranscriptome to ensure protein translation fidelity.

Published
2022

45. Clinical impact of STK11 mutation in advanced-stage non-small cell lung cancer

Author

Rosellini, Pietro, primary, Amintas, Samuel, additional, Caumont, Charline, additional, Veillon, Rémi, additional, Galland-Girodet, Sigolène, additional, Cuguillière, Alain, additional, Nguyen, Laurent, additional, Domblides, Charlotte, additional, Gouverneur, Amandine, additional, Merlio, Jean-Philippe, additional, Bezin, Julien, additional, and Girodet, Pierre-Olivier, additional

Published
2022
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46. Elp3‐mediated codon‐dependent translation promotes mTORC2 activation and regulates macrophage polarization

Author

Chen, Dawei, primary, Nemazanyy, Ivan, additional, Peulen, Olivier, additional, Shostak, Kateryna, additional, Xu, Xinyi, additional, Tang, Seng Chuan, additional, Wathieu, Caroline, additional, Turchetto, Silvia, additional, Tielens, Sylvia, additional, Nguyen, Laurent, additional, Close, Pierre, additional, Desmet, Christophe, additional, Klein, Sebastian, additional, Florin, Alexandra, additional, Büttner, Reinhard, additional, Petrellis, Georgios, additional, Dewals, Benjamin, additional, and Chariot, Alain, additional

Published
2022
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