Targeting IRE1 in disease

Project Information

INSPIRED

Grant agreement ID: 734749

DOI 10.3030/734749

Project closed

EC signature date 28 October 2016

Start date 1 January 2017

End date 30 June 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost € 886 500,00

EU contribution € 832 500,00

Coordinated by

UNIVERSITY OF GALWAY
Ireland

Deliverables

Websites, patent fillings, videos etc. (2)

Consortium web site established
Creation of Facebook & Twitter accounts

Publications

Peer reviewed articles (35)

Tumour Cell Secretome in Chemoresistance and Tumour Recurrence

Author(s): Emma C. Madden, Adrienne M. Gorman, Susan E. Logue, Afshin Samali
Published in: Trends in Cancer, Issue 6/6, 2020, Page(s) 489-505, ISSN 2405-8033
Publisher: Cell Press
DOI: 10.1016/j.trecan.2020.02.020

Pharmacological Targeting of IRE1 in Cancer

Author(s): Diana Pelizzari Raymundo, Dimitrios Doultsinos, Xavier Guillory, Antonio Carlesso, Leif A. Eriksson, Eric Chevet
Published in: Trends in Cancer, Issue 6/12, 2020, Page(s) 1018-1030, ISSN 2405-8033
Publisher: Cell Press
DOI: 10.1016/j.trecan.2020.07.006

The unfolded protein response modulators GSK2606414 and KIRA6 are potent KIT inhibitors

Author(s): Mohamed Mahameed, Thomas Wilhelm, Odai Darawshi, Akram Obiedat, Weiss-Sadan Tommy, Chetan Chintha, Thomas Schubert, Afshin Samali, Eric Chevet, Leif A. Eriksson, Michael Huber, Boaz Tirosh
Published in: Cell Death & Disease, Issue 10/4, 2019, ISSN 2041-4889
Publisher: Nature Publishing Group
DOI: 10.1038/s41419-019-1523-3

Regulation of lipid metabolism by the unfolded protein response

Author(s): Matthieu Moncan, Katarzyna Mnich, Arnaud Blomme, Aitor Almanza, Afshin Samali, Adrienne M. Gorman
Published in: Journal of Cellular and Molecular Medicine, Issue 25/3, 2021, Page(s) 1359-1370, ISSN 1582-1838
Publisher: Wiley-Blackwell
DOI: 10.1111/jcmm.16255

New insights on human IRE1 tetramer structures based on molecular modeling

Author(s): Antonio Carlesso, Johanna Hörberg, Anna Reymer, Leif A. Eriksson
Published in: Scientific Reports, Issue 10/1, 2020, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-74347-8

When Endoplasmic Reticulum Proteostasis Meets the DNA Damage Response

Author(s): Matías González-Quiroz, Alice Blondel, Alfredo Sagredo, Claudio Hetz, Eric Chevet, Rémy Pedeux
Published in: Trends in Cell Biology, Issue 30/11, 2020, Page(s) 881-891, ISSN 0962-8924
Publisher: Elsevier BV
DOI: 10.1016/j.tcb.2020.09.002

Deciphering the selectivity of inhibitor MKC9989 towards residue K907 in IRE1α; a multiscale in silico approach

Author(s): Sayyed Jalil Mahdizadeh, Antonio Carlesso, Leif A. Eriksson
Published in: RSC Advances, Issue 10/33, 2020, Page(s) 19720-19729, ISSN 2046-2069
Publisher: Royal Society of Chemistry
DOI: 10.1039/d0ra01895c

Reconstruction of the Fas-Based Death-Inducing Signaling Complex (DISC) Using a Protein–Protein Docking Meta-Approach

Author(s): Sayyed Jalil Mahdizadeh, Melissa Thomas, Leif A. Eriksson
Published in: Journal of Chemical Information and Modeling, Issue 61/7, 2021, Page(s) 3543-3558, ISSN 1549-9596
Publisher: American Chemical Society
DOI: 10.1021/acs.jcim.1c00301

Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease

Author(s): Cynthia Lebeaupin, Deborah Vallée, Younis Hazari, Claudio Hetz, Eric Chevet, Béatrice Bailly-Maitre
Published in: Journal of Hepatology, Issue 69/4, 2018, Page(s) 927-947, ISSN 0168-8278
Publisher: Elsevier BV
DOI: 10.1016/j.jhep.2018.06.008

Control of anterior GR adient 2 ( AGR 2) dimerization links endoplasmic reticulum proteostasis to inflammation

Author(s): Marion Maurel, Joanna Obacz, Tony Avril, Yong‐Ping Ding, Olga Papadodima, Xavier Treton, Fanny Daniel, Eleftherios Pilalis, Johanna Hörberg, Wenyang Hou, Marie‐Claude Beauchamp, Julien Tourneur‐Marsille, Dominique Cazals‐Hatem, Lucia Sommerova, Afshin Samali, Jan Tavernier, Roman Hrstka, Aurélien Dupont, Delphine Fessart, Frédéric Delom, Martin E Fernandez‐Zapico, Gregor Jansen, Leif
Published in: EMBO Molecular Medicine, Issue 11/6, 2019, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.201810120

Control of Protein Homeostasis in the Early Secretory Pathway: Current Status and Challenges

Author(s): Daria Sicari, Aeid Igbaria, Eric Chevet
Published in: Cells, Issue 8/11, 2019, Page(s) 1347, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells8111347

Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics

Author(s): Amado Carreras-Sureda, Fabián Jaña, Hery Urra, Sylvere Durand, David E. Mortenson, Alfredo Sagredo, Galdo Bustos, Younis Hazari, Eva Ramos-Fernández, Maria L. Sassano, Philippe Pihán, Alexander R. van Vliet, Matías González-Quiroz, Angie K. Torres, Cheril Tapia-Rojas, Martijn Kerkhofs, Rubén Vicente, Randal J. Kaufman, Nibaldo C. Inestrosa, Christian Gonzalez-Billault, R. Luke Wiseman, Patr
Published in: Nature Cell Biology, Issue 21/6, 2019, Page(s) 755-767, ISSN 1465-7392
Publisher: Nature Publishing Group
DOI: 10.1038/s41556-019-0329-y

Peptidomimetic‐based identification of FDA‐approved compounds inhibiting IRE1 activity

Author(s): Dimitrios Doultsinos, Antonio Carlesso, Chetan Chintha, James C. Paton, Adrienne W. Paton, Afshin Samali, Eric Chevet, Leif A. Eriksson
Published in: The FEBS Journal, Issue 288/3, 2021, Page(s) 945-960, ISSN 1742-464X
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/febs.15372

The UPRosome – decoding novel biological outputs of IRE1α function

Author(s): Hery Urra, Philippe Pihán, Claudio Hetz
Published in: Journal of Cell Science, Issue 133/15, 2020, ISSN 0021-9533
Publisher: The Company of Biologists Ltd.
DOI: 10.1242/jcs.218107

The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability

Author(s): Viviana Pérez, Francisca Bermedo-Garcia, Diego Zelada, Felipe A. Court, Miguel Ángel Pérez, Marco Fuenzalida, Johanna Ábrigo, Claudio Cabello-Verrugio, Guillermo Moya-Alvarado, Juan Carlos Tapia, Vicente Valenzuela, Claudio Hetz, Francisca C. Bronfman, Juan Pablo Henríquez
Published in: Acta Neuropathologica Communications, Issue 7/1, 2019, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-019-0802-7

Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α

Author(s): Denisse Sepulveda, Diego Rojas-Rivera, Diego A. Rodríguez, Jody Groenendyk, Andres Köhler, Cynthia Lebeaupin, Shinya Ito, Hery Urra, Amado Carreras-Sureda, Younis Hazari, Mireille Vasseur-Cognet, Maruf M.U. Ali, Eric Chevet, Gisela Campos, Patricio Godoy, Tomas Vaisar, Béatrice Bailly-Maitre, Kazuhiro Nagata, Marek Michalak, Jimena Sierralta, Claudio Hetz
Published in: Molecular Cell, Issue 69/2, 2018, Page(s) 238-252.e7, ISSN 1097-2765
Publisher: Cell Press
DOI: 10.1016/j.molcel.2017.12.028

Dual IRE1 RNase functions dictate glioblastoma development

Author(s): Stéphanie Lhomond, Tony Avril, Nicolas Dejeans, Konstantinos Voutetakis, Dimitrios Doultsinos, Mari McMahon, Raphaël Pineau, Joanna Obacz, Olga Papadodima, Florence Jouan, Heloise Bourien, Marianthi Logotheti, Gwénaële Jégou, Néstor Pallares‐Lupon, Kathleen Schmit, Pierre‐Jean Le Reste, Amandine Etcheverry, Jean Mosser, Kim Barroso, Elodie Vauléon, Marion Maurel, Afshin Samali, John B P
Published in: EMBO Molecular Medicine, Issue 10/3, 2018, Page(s) e7929, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.201707929

Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy

Author(s): Susan E. Logue, Eoghan P. McGrath, Patricia Cleary, Stephanie Greene, Katarzyna Mnich, Aitor Almanza, Eric Chevet, Róisín M. Dwyer, Anup Oommen, Patrick Legembre, Florence Godey, Emma C. Madden, Brian Leuzzi, Joanna Obacz, Qingping Zeng, John B. Patterson, Richard Jäger, Adrienne M. Gorman, Afshin Samali
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-018-05763-8

Regulation of tumor-stroma interactions by the unfolded protein response

Author(s): Joanna Obacz, Tony Avril, Camila Rubio-Patiño, Jozef P. Bossowski, Aeid Igbaria, Jean-Ehrland Ricci, Eric Chevet
Published in: The FEBS Journal, 2017, ISSN 1742-464X
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/febs.14359

The Unfolded Protein Response: At the Intersection between Endoplasmic Reticulum Function and Mitochondrial Bioenergetics

Author(s): Amado Carreras-Sureda, Philippe Pihán, Claudio Hetz
Published in: Frontiers in Oncology, Issue 7, 2017, ISSN 2234-943X
Publisher: Frontiers Media S. A.
DOI: 10.3389/fonc.2017.00055

Fine-Tuning ER Stress Signal Transducers to Treat Amyotrophic Lateral Sclerosis

Author(s): Danilo B. Medinas, Jose V. González, Paulina Falcon, Claudio Hetz
Published in: Frontiers in Molecular Neuroscience, Issue 10, 2017, ISSN 1662-5099
Publisher: Frontiers Research Foundation
DOI: 10.3389/fnmol.2017.00216

Drug repurposing to target proteostasis and prevent neurodegeneration: accelerating translational efforts

Author(s): Gabriela Mercado, Claudio Hetz
Published in: Brain, Issue 140/6, 2017, Page(s) 1544-1547, ISSN 0006-8950
Publisher: Oxford University Press
DOI: 10.1093/brain/awx107

Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications

Author(s): Aitor Almanza, Antonio Carlesso, Chetan Chintha, Stuart Creedican, Dimitrios Doultsinos, Brian Leuzzi, Andreia Luís, Nicole McCarthy, Luigi Montibeller, Sanket More, Alexandra Papaioannou, Franziska Püschel, Maria Livia Sassano, Josip Skoko, Patrizia Agostinis, Jackie de Belleroche, Leif A. Eriksson, Simone Fulda, Adrienne M. Gorman, Sandra Healy, Andrey Kozlov, Cristina Muñoz-Pinedo, Markus Re
Published in: The FEBS Journal, Issue 286/2, 2019, Page(s) 241-278, ISSN 1742-464X
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/febs.14608

The Unfolded Protein Response and Cell Fate Control

Author(s): Claudio Hetz, Feroz R. Papa
Published in: Molecular Cell, Issue 69/2, 2018, Page(s) 169-181, ISSN 1097-2765
Publisher: Cell Press
DOI: 10.1016/j.molcel.2017.06.017

BCL-2 family: integrating stress responses at the ER to control cell demise

Author(s): Philippe Pihán, Amado Carreras-Sureda, Claudio Hetz
Published in: Cell Death and Differentiation, Issue 24/9, 2017, Page(s) 1478-1487, ISSN 1350-9047
Publisher: Nature Publishing Group
DOI: 10.1038/cdd.2017.82

Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315T ALS/FTD mouse model

Author(s): Leslie Bargsted, Danilo B. Medinas, Francisca Martínez Traub, Pablo Rozas, Natalia Muñoz, Melissa Nassif, Carolina Jerez, Alejandra Catenaccio, Felipe A. Court, Claudio Hetz, Soledad Matus
Published in: Scientific Reports, Issue 7/1, 2017, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-017-14399-5

The Unfolded Protein Response in Breast Cancer

Author(s): Eoghan McGrath, Susan Logue, Katarzyna Mnich, Shane Deegan, Richard Jäger, Adrienne Gorman, Afshin Samali
Published in: Cancers, Issue 10/10, 2018, Page(s) 344, ISSN 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers10100344

IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A

Author(s): Hery Urra, Daniel R. Henriquez, José Cánovas, David Villarroel-Campos, Amado Carreras-Sureda, Eduardo Pulgar, Emiliano Molina, Younis M. Hazari, Celia M. Limia, Sebastián Alvarez-Rojas, Ricardo Figueroa, Rene L. Vidal, Diego A. Rodriguez, Claudia A. Rivera, Felipe A. Court, Andrés Couve, Ling Qi, Eric Chevet, Ryoko Akai, Takao Iwawaki, Miguel L. Concha, Álvaro Glavic, Christian Gonzalez-Billa
Published in: Nature Cell Biology, Issue 20/8, 2018, Page(s) 942-953, ISSN 1465-7392
Publisher: Nature Publishing Group
DOI: 10.1038/s41556-018-0141-0

A guide to assessing endoplasmic reticulum homeostasis and stress in mammalian systems

Author(s): Daria Sicari, Agnès Delaunay‐Moisan, Laurent Combettes, Eric Chevet, Aeid Igbaria
Published in: The FEBS Journal, Issue 287/1, 2019, Page(s) 27-42, ISSN 1742-464X
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/febs.15107

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

Author(s): Maritza Oñate, Alejandra Catenaccio, Natalia Salvadores, Cristian Saquel, Alexis Martinez, Ines Moreno-Gonzalez, Nazaret Gamez, Paulina Soto, Claudio Soto, Claudio Hetz, Felipe A. Court
Published in: Cell Death & Differentiation, Issue 27/4, 2020, Page(s) 1169-1185, ISSN 1350-9047
Publisher: Nature Publishing Group
DOI: 10.1038/s41418-019-0408-4

Molecular modeling provides a structural basis for PERK inhibitor selectivity towards RIPK1

Author(s): Chetan Chintha, Antonio Carlesso, Adrienne M. Gorman, Afshin Samali, Leif A. Eriksson
Published in: RSC Advances, Issue 10/1, 2020, Page(s) 367-375, ISSN 2046-2069
Publisher: Royal Society of Chemistry
DOI: 10.1039/c9ra08047c

CD90/Thy-1, a Cancer-Associated Cell Surface Signaling Molecule

Author(s): Chloé Sauzay, Konstantinos Voutetakis, Aristotelis Chatziioannou, Eric Chevet, Tony Avril
Published in: Frontiers in Cell and Developmental Biology, Issue 7, 2019, ISSN 2296-634X
Publisher: Frontiers
DOI: 10.3389/fcell.2019.00066

Role of the early secretory pathway in SARS-CoV-2 infection

Author(s): Daria Sicari, Aristotelis Chatziioannou, Theodoros Koutsandreas, Roberto Sitia, Eric Chevet
Published in: Journal of Cell Biology, Issue 219/9, 2020, ISSN 0021-9525
Publisher: Rockefeller University Press
DOI: 10.1083/jcb.202006005

Emerging Roles of the Endoplasmic Reticulum Associated Unfolded Protein Response in Cancer Cell Migration and Invasion

Author(s): Celia Limia, Chloé Sauzay, Hery Urra, Claudio Hetz, Eric Chevet, Tony Avril
Published in: Cancers, Issue 11/5, 2019, Page(s) 631, ISSN 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers11050631

Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response

Author(s): Estefanie Dufey, José Manuel Bravo-San Pedro, Cristian Eggers, Matías González-Quiroz, Hery Urra, Alfredo I. Sagredo, Denisse Sepulveda, Philippe Pihán, Amado Carreras-Sureda, Younis Hazari, Eduardo A. Sagredo, Daniela Gutierrez, Cristian Valls, Alexandra Papaioannou, Diego Acosta-Alvear, Gisela Campos, Pedro M. Domingos, Rémy Pedeux, Eric Chevet, Alejandra Alvarez, Patricio Godoy, Peter Walt
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-15694-y