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Subject collection: Model Systems in Drug Discovery

  • PERSPECTIVE
    Modeling the developmental origins of pediatric cancer to improve patient outcomes
    James F. Amatruda
    Disease Models & Mechanisms 2021 14: dmm048930 doi: 10.1242/dmm.048930 Published 22 February 2021

    Summary: This Perspective discusses the special features that make it challenging to develop new therapies for pediatric cancers, and the ways in which collaboration centered on improved models can meet these challenges.

  • RESEARCH ARTICLE
    Head-to-head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL2Rγnull mice reconstituted with human peripheral blood mononuclear cells
    Henrika Jodeleit, Paula Winkelmann, Janina Caesar, Sebastian Sterz, Lesca M. Holdt, Florian Beigel, Johannes Stallhofer, Simone Breiteneicher, Eckart Bartnik, Thomas Leeuw, Matthias Siebeck, Roswitha Gropp
    Disease Models & Mechanisms 2021 14: dmm046995 doi: 10.1242/dmm.046995 Published 21 January 2021

    Summary: The combination of patient profiling and testing in a NOD/Scid IL2Rγnull mouse model of ulcerative colitis (UC) validates oxelumab as a potential therapeutic in UC.

  • RESEARCH ARTICLE
    Alcoholic hepatitis and metabolic disturbance in female mice: a more tractable model than Nrf2−/− animals
    Lozan Sheriff, Reenam S. Khan, Raquel Saborano, Richard Wilkin, Nguyet-Thin Luu, Ulrich L. Gunther, Stefan G. Hubscher, Philip N. Newsome, Patricia F. Lalor
    Disease Models & Mechanisms 2020 13: dmm046383 doi: 10.1242/dmm.046383 Published 29 December 2020

    Summary: We describe a simple murine model of alcoholic hepatitis (AH) to induce injury that recreates many of the key features of AH in human, without the need of challenging surgical procedures to administer ethanol. This will be valuable for testing new therapeutic treatments.

  • RESEARCH ARTICLE
    Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease
    Katie Lloyd, Stamatia Papoutsopoulou, Emily Smith, Philip Stegmaier, Francois Bergey, Lorna Morris, Madeleine Kittner, Hazel England, Dave Spiller, Mike H. R. White, Carrie A. Duckworth, Barry J. Campbell, Vladimir Poroikov, Vitor A. P. Martins dos Santos, Alexander Kel, Werner Muller, D. Mark Pritchard, Chris Probert, Michael D. Burkitt, The SysmedIBD Consortium
    Disease Models & Mechanisms 2020 13: dmm044040 doi: 10.1242/dmm.044040 Published 27 November 2020

    Summary: Using state-of-the-art in silico drug discovery and real-time live-cell imaging techniques, we identify clarithromycin as a drug with potential for repositioning for inflammatory bowel disease.

  • RESEARCH ARTICLE
    An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy
    Pingtao Tang, Jharna R. Das, Jinliang Li, Jing Yu, Patricio E. Ray
    Disease Models & Mechanisms 2020 13: dmm045641 doi: 10.1242/dmm.045641 Published 28 October 2020

    Summary: The development of a new inducible mouse model system of childhood HIV-associated nephropathy demonstrated that HIV-Tat plays a critical role in this disease, acting in synergy with other HIV-1 genes and heparin-binding cytokines.

  • REVIEW
    Cellular and animal models for facioscapulohumeral muscular dystrophy
    Alec M. DeSimone, Justin Cohen, Monkol Lek, Angela Lek
    Disease Models & Mechanisms 2020 13: dmm046904 doi: 10.1242/dmm.046904 Published 28 October 2020

    Summary: Owing to its complex etiology and the toxicity of DUX4, modeling facioscapulohumeral muscular dystrophy (FSHD) is uniquely challenging. Here, we review the approaches that overcame these difficulties to develop highly relevant FSHD models.

  • AT A GLANCE
    Modeling neurodegeneration in Caenorhabditis elegans
    Kim A. Caldwell, Corey W. Willicott, Guy A. Caldwell
    Disease Models & Mechanisms 2020 13: dmm046110 doi: 10.1242/dmm.046110 Published 26 October 2020

    Summary: While unsurpassed as an experimental system for fundamental biology, Caenorhabditis elegans remains undervalued for its translational potential. Here, we highlight significant outcomes from, and resources available for, C. elegans-based research into neurodegenerative disorders.

  • RESEARCH ARTICLE
    Pre-existing antibody-mediated adverse effects prevent the clinical development of a bacterial anti-inflammatory protein
    Angelino T. Tromp, Yuxi Zhao, Ilse Jongerius, Erik C. J. M. Heezius, Pauline Abrial, Maartje Ruyken, Jos A. G. van Strijp, Carla J. C. de Haas, András N. Spaan, Kok P. M. van Kessel, Thomas Henry, Pieter-Jan A. Haas
    Disease Models & Mechanisms 2020 13: dmm045534 doi: 10.1242/dmm.045534 Published 28 September 2020

    Summary: Chemotaxis inhibitory protein of Staphylococcus aureus dampens C5a-mediated responses in human-C5aR1 knock-in mice. Feasibility studies in a human phase I trial failed due to high levels of existing natural antibodies causing adverse effects.

  • REVIEW
    Integrating fish models in tuberculosis vaccine development
    Anni K. Saralahti, Meri I. E. Uusi-Mäkelä, Mirja T. Niskanen, Mika Rämet
    Disease Models & Mechanisms 2020 13: dmm045716 doi: 10.1242/dmm.045716 Published 23 August 2020

    Summary: In this Review, we discuss how zebrafish (Danio rerio) and other fish models can complement the more traditional mammalian models in the development of novel vaccines against tuberculosis.

  • REVIEW
    Neuromuscular disease modeling on a chip
    Jeffrey W. Santoso, Megan L. McCain
    Disease Models & Mechanisms 2020 13: dmm044867 doi: 10.1242/dmm.044867 Published 7 July 2020

    Summary: Modeling neuromuscular diseases is challenging due to their complex etiology and pathophysiology. Here, we review the cell sources and tissue-engineering procedures that are being integrated as emerging neuromuscular disease models.

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