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Your search keyword '"Istituto Nazionale Genetica Molecolare [Milano] (INGM)"' showing total 4 results
Start Over Author "Istituto Nazionale Genetica Molecolare [Milano] (INGM)" Topic cell biology
4 results on '"Istituto Nazionale Genetica Molecolare [Milano] (INGM)"'

1. Elevated TGF β2 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes

Author

Nicola Carboni, Chiara Lanzuolo, Elisa Schena, Lucio Santoro, Tiziana Mongini, Elena Biagini, Lucia Morandi, Gisèle Bonne, Giovanna Lattanzi, Lorenzo Maggi, Patrizia Sabatelli, Giulia Ricci, Lucia Ruggiero, Cristina Cappelletti, Marta Columbaro, Luisa Politano, Antoine Muchir, Giuseppe Boriani, Camilla Evangelisti, Sabino Prencipe, Gabriele Siciliano, Elena Pegoraro, Pia Bernasconi, Paola Cavalcante, Liliana Vercelli, Carmelo Rodolico, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Pisa - Università di Pisa, Second University of Naples-Caserta, University of Naples Federico II, University of Turin, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Università degli Studi di Modena e Reggio Emilia, Universita degli Studi di Padova, Istituto Nazionale Genetica Molecolare [Milano] (INGM), Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Bernasconi, Pia, Carboni, Nicola, Ricci, Giulia, Siciliano, Gabriele, Politano, Luisa, Maggi, Lorenzo, Mongini, Tiziana, Vercelli, Liliana, Rodolico, Carmelo, Biagini, Elena, Boriani, Giuseppe, Ruggiero, Lucia, Santoro, Lucio, Schena, Elisa, Prencipe, Sabino, Evangelisti, Camilla, Pegoraro, Elena, Morandi, Lucia, Columbaro, Marta, Lanzuolo, Chiara, Sabatelli, Patrizia, Cavalcante, Paola, Cappelletti, Cristina, Bonne, Gisèle, Muchir, Antoine, Lattanzi, Giovanna, Bernasconi P., Carboni N., Ricci G., Siciliano G., Politano L., Maggi L., Mongini T., Vercelli L., Rodolico C., Biagini E., Boriani G., Ruggiero L., Santoro L., Schena E., Prencipe S., Evangelisti C., Pegoraro E., Morandi L., Columbaro M., Lanzuolo C., Sabatelli P., Cavalcante P., Cappelletti C., Bonne G., Muchir A., and Lattanzi G.

Subjects
0301 basic medicine, Male, Basic fibroblast growth factor, LMNA, chemistry.chemical_compound, Mice, Transforming growth factor beta 2 (TGF b2), Medicine, Muscular Dystrophy, Muscular dystrophy, Emery–Dreifuss muscular dystrophy, LMNA gene, Cells, Cultured, lamin A/C, muscle fibrosis, Mice, Knockout, Cultured, tendon fibrosis, biology, Myogenesis, Emery-Dreifuss, Cell Differentiation, Middle Aged, Muscular Dystrophy, Emery-Dreifuss, 3. Good health, Laminopathie, Transforming growth factor beta 2 (TGF β2), Fibroblast, Female, Interleukin 17, Human, musculoskeletal diseases, Adult, Cells, Knockout, Muscle Cell, Dilated Cardiomyopathy (CMD1A), Emery-Dreifuss Muscular Dystrophy type 2 (EDMD2), Laminopathies, Limb-Girdle muscular Dystrophy 1B (LGMD1B), muscular differentiation, 03 medical and health sciences, Transforming Growth Factor beta2, Young Adult, Lamin A/C, Muscle fibrosis, Muscular differentiation, Tendon fibrosis, Animals, Fibroblasts, Humans, Muscle Cells, Tenocytes, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Interleukin 6, Animal, Muscular Dystrophy, Emery-Dreifu, business.industry, muscle fibrosi, Cell Biology, Transforming growth factor beta, Tenocyte, medicine.disease, 030104 developmental biology, chemistry, biology.protein, Cancer research, business, Tendon fibrosi, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF β2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF β2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss Muscular Dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF β2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF β2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF β2-dependent mechanisms were also determined in laminopathic cells, where TGF β2 activated AKT/mTOR phosphorylation. These data show that TGF β2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.

Published
2018
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2. Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth

Author

Giuseppe Matarese, Nico Mitro, Massimiliano Pagani, Martina Severa, Chiara Focaccetti, Yu Wei, Eliana M. Coccia, Stefano Miacci, Silvia Piconese, Eleonora Timperi, Claudio Procaccini, Giuseppe Danilo Norata, Ilenia Pacella, Valeria Ranzani, Vincenzo Barnaba, Fabiana Rizzo, Grazisa Rossetti, Fabrizia Bonacina, Ezio Giorda, Deriggio Faicchia, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Consiglio Nazionale delle Ricerche [Napoli] (CNR), Istituto Superiore di Sanità (ISS), Università degli Studi di Milano = University of Milan (UNIMI), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Istituto Nazionale Genetica Molecolare [Milano] (INGM), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pathogenèse des Virus de l'Hépatite B (PVHB), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Naples Federico II = Università degli studi di Napoli Federico II, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Istituto Italiano di Tecnologia (IIT), This work was supported by Associazione Italiana per la Ricerca sul Cancro Grants IG-2014 15199 and IG-2017 19939 (to V.B.) and IG-2017 19784 (to S.P.), Ministry of Education, University and Research (MIUR) Grants RF-2010-2310438 and RF 2010-2318269, Fondazione Italiana Sclerosi Multipla Grants code 2015/R/04 (to V.B.), code 2013/R/9 (to E.M.C.), code 2016/R/18 (to G.M.), and code 2014/R/19 (to M.S.), MIUR Progetti di Ricerca di Interesse Nazionale Grant 2010-2011 protocol 2010LC747T_004, MIUR Fondo per gli Investimenti della Ricerca di Base 2011/13 Grant no. RBAP10TPXK, Istituto Pasteur Italia–Fondazione Cenci Bolognetti Grant 2014-2016, International Network Institut Pasteur Programmes Transversaux de Recherche Grant 20-16, Fondazione Roma Grant for Biomedical Research NCDS-2013-000000345, the European Union’s Seventh Framework Program (FP7) under Grant Agreement 259743 (MODHEP consortium) (to Y.W.), Fondazione Cariplo Grant 2016-0852 (to G.D.N.), Ministero della Salute Grants GR-2011-02346974 (to G.D.N.) and GR-2013-02355011 (to F.B.), and European Union IDEAS Programme European Research Council Starting Grant menTORingTregs 310496 and Telethon Grant GGP17086 (to G.M.). C.F. was supported by a 2015 Fellowship from Fondazione Veronesi., European Project: 259743,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,MODHEP(2011), European Project: 310496,EC:FP7:ERC,ERC-2012-StG_20111109,MENTORINGTREGS(2013), Pacella, Ilenia, Procaccini, Claudio, Focaccetti, Chiara, Miacci, Stefano, Timperi, Eleonora, Faicchia, Deriggio, Severa, Martina, Rizzo, Fabiana, Coccia, Eliana Marina, Bonacina, Fabrizia, Mitro, Nico, Norata, Giuseppe Danilo, Rossetti, Grazisa, Ranzani, Valeria, Pagani, Massimiliano, Giorda, Ezio, Wei, Yu, Matarese, Giuseppe, Barnaba, Vincenzo, Piconese, Silvia, Istituto Superiore di Sanita [Rome], Systems biology of liver cancer: an integrative genomic-epigenomic approach - MODHEP - - EC:FP7:HEALTH2011-01-01 - 2016-06-30 - 259743 - VALID, Unravelling paradoxes in regulatory T cell biology: the molecular basis for an mTOR-dependent oscillatory metabolic switch controlling immune tolerance and autoimmunity - MENTORINGTREGS - - EC:FP7:ERC2013-05-01 - 2018-04-30 - 310496 - VALID, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Milano [Milano] (UNIMI), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Napoli Federico II

Subjects
0301 basic medicine, MESH: Neoplasm Proteins, MESH: Oxidation-Reduction, Treg, fatty acid synthesis, glycolysis, ox40, tumor microenvironment, Glycolysi, T-Lymphocytes, Type I, Settore MED/04, T-Lymphocytes, Regulatory, Transgenic, chemistry.chemical_compound, Mice, 0302 clinical medicine, Neoplasms, MESH: Tumor Microenvironment, Glycolysis, MESH: Animals, Tumor, Multidisciplinary, Chemistry, Fatty Acids, hemic and immune systems, Regulatory, Cell biology, Neoplasm Proteins, MESH: Fatty Acids, Fatty Acid Synthase, Type I, medicine.anatomical_structure, MESH: Neoplasms, Experimental, PNAS Plus, Fatty Acid Synthase, 030220 oncology & carcinogenesis, MESH: Glycolysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Fatty Acid Synthase, Type I, Fatty acid synthesis, Ox40, Tumor microenvironment, Animals, Cell Line, Tumor, Humans, Mice, Transgenic, Neoplasms, Experimental, Oxidation-Reduction, Tumor Microenvironment, Intracellular, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Regulatory T cell, MESH: Mice, Transgenic, T cell, chemical and pharmacologic phenomena, Cell Line, 03 medical and health sciences, Experimental, Fatty acid synthesi, medicine, MESH: Mice, MESH: Humans, Fatty acid metabolism, MESH: T-Lymphocytes, Regulatory, Lipid metabolism, 030104 developmental biology
Abstract

International audience; The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment.

Published
2018
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3. Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology

Author

Francesco Marabita, David Gomez-Cabrero, Jesper Tegnér, Josep Roca, Ana Conesa, Philippe Sabatier, Isaac Cano, Sonia Tarazona, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Centro de Genómica - Centre de Genòmica [IVIA], Instituto Valenciano de Investigaciones Agrarias - Institut Valencià d'Investigacions Agraries - Valencian Institute for agricultural Research (IVIA), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 [2016-2019] (UGA [2016-2019]), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 [2016-2019] (UGA [2016-2019]), Computational Biology Unit, Linköping University (LIU), and ZOPPIS, Catherine

Subjects
0301 basic medicine, Health Knowledge, Attitudes, Practice, Engineering, Systems Analysis, Histology, Knowledge management, Systems biology, [SDV]Life Sciences [q-bio], ESTADISTICA E INVESTIGACION OPERATIVA, MEDLINE, Interdisciplinary Studies, Nature versus nurture, Education, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, ComputingMilieux_COMPUTERSANDEDUCATION, Humans, Students, Curriculum, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Systems Biology, 4. Education, Interdisciplinary learning, Cell Biology, Research Personnel, 3. Good health, [SDV] Life Sciences [q-bio], Systems medicine, 030104 developmental biology, Systems analysis, Engineering ethics, business, 030217 neurology & neurosurgery
Abstract

[EN] Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there., The authors would like to acknowledge helpful comments from the editor. J.T. was supported by EU FP7 305033 CASyM and King Abdullah University for Science and Technology. D.G., F.M., S.T, A.C., and J.T. were supported by EU FP7 306000 STATegra

Published
2017

4. Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture

Author

Daniel Gotthardt, Paul Schnitzler, Max Meyrath, Petra Neddermann, Ralf Bartenschlager, Inés Romero-Brey, Katharina Esser-Nobis, Philip Meuleman, Robert Thimme, Charles M. Rice, Christian Schenk, Florian W. R. Vondran, Claire Gondeau, Christian Harak, Mohsan Saeed, Raffaele De Francesco, Philipp Schult, Volker Lohmann, Sofía Pérez-del-Pulgar, Christoph Neumann-Haefelin, Universität Heidelberg [Heidelberg], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Rockefeller University [New York], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Heidelberg University Hospital [Heidelberg], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University Hospital Freiburg, Ghent University Hospital, Hannover Medical School [Hannover] (MHH), and This project was funded by grants from the Deutsche Forschungsgemeinschaft (LO 1556/1-2, LO 1556/4-1 and TRR77, TPA1 to V.L., and TRR83, TP13 and TRR77, TPA1 to R.B.), as well as an HBIGS Postdoc stipend to C.H. This work was supported in part by the National Institutes of Health National Cancer Institute grant R01CA057973 and National Institute of Allergy and Infectious Diseases grants R01AI072613 and R01AI099284 (to C.M.R.) and by a Helmsley Postdoctoral Fellowship for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University (to M.S.). The Greenberg Medical Research Institute, Starr Foundation, Ronald A. Shellow, M.D. Memorial Fund and anonymous donors provided additional funding (to C.M.R.).

Subjects
0301 basic medicine, Microbiology (medical), Phosphatidylinositol 4-phosphate, [SDV]Life Sciences [q-bio], Hepatitis C virus, Immunology, Biology, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, Virus, 03 medical and health sciences, chemistry.chemical_compound, Genetics, medicine, Kinase activity, Kinase, Cell Biology, Virology, digestive system diseases, 3. Good health, NS2-3 protease, 030104 developmental biology, chemistry, Carcinogenesis, PI4KA
Abstract

With a single exception, all isolates of hepatitis C virus (HCV) require adaptive mutations to replicate efficiently in cell culture. Here, we show that a major class of adaptive mutations regulates the activity of a cellular lipid kinase, phosphatidylinositol 4-kinase IIIα (PI4KA). HCV needs to stimulate PI4KA to create a permissive phosphatidylinositol 4-phosphate-enriched membrane microenvironment in the liver and in primary human hepatocytes (PHHs). In contrast, in Huh7 hepatoma cells, the virus must acquire loss-of-function mutations that prevent PI4KA overactivation. This adaptive mechanism is necessitated by increased PI4KA levels in Huh7 cells compared with PHHs, and is conserved across HCV genotypes. PI4KA-specific inhibitors promote replication of unadapted viral isolates and allow efficient replication of patient-derived virus in cell culture. In summary, this study has uncovered a long-sought mechanism of HCV cell-culture adaptation and demonstrates how a virus can adapt to changes in a cellular environment associated with tumorigenesis.

Published
2016
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