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Subject collection: Model Systems in Drug Discovery

  • RESOURCE ARTICLE
    Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia
    Karim Si-Tayeb, Salam Idriss, Benoite Champon, Amandine Caillaud, Matthieu Pichelin, Lucie Arnaud, Patricia Lemarchand, Cédric Le May, Kazem Zibara, Bertrand Cariou
    Disease Models & Mechanisms 2016 9: 81-90; doi: 10.1242/dmm.022277

    Summary: The authors used urine-sample-derived patient-specific human induced pluripotent stem cells to generate hepatocytes carrying gain- or loss-of-function mutations of PCSK9, and mimicking the pathophysiology in vitro.

  • RESEARCH ARTICLE
    T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice
    Ceri E. Oldreive, Anna Skowronska, Nicholas J. Davies, Helen Parry, Angelo Agathanggelou, Sergey Krysov, Graham Packham, Zbigniew Rudzki, Laura Cronin, Katerina Vrzalikova, Paul Murray, Elena Odintsova, Guy Pratt, A. Malcolm R. Taylor, Paul Moss, Tatjana Stankovic
    Disease Models & Mechanisms 2015 8: 1401-1412; doi: 10.1242/dmm.021147

    Summary: Manipulation of T cells can enhance current CLL xenograft models, expanding their utility for investigation of tumour biology and pre-clinical drug assessment.

  • REVIEW
    GEMMs as preclinical models for testing pancreatic cancer therapies
    Aarthi Gopinathan, Jennifer P. Morton, Duncan I. Jodrell, Owen J. Sansom
    Disease Models & Mechanisms 2015 8: 1185-1200; doi: 10.1242/dmm.021055

    Drug Discovery Collection: This Review discusses GEMMs of human pancreatic cancer, particularly focusing on the KPC model, its use in preclinical research, advantages and disadvantages, and its potential for predicting clinical outcomes.

  • RESEARCH ARTICLE
    A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics
    Ozhan Ocal, Victor Pashkov, Rahul K. Kollipara, Yalda Zolghadri, Victoria H. Cruz, Michael A. Hale, Blake R. Heath, Alex B. Artyukhin, Alana L. Christie, Pantelis Tsoulfas, James B. Lorens, Galvin H. Swift, Rolf A. Brekken, Thomas M. Wilkie
    Disease Models & Mechanisms 2015 8: 1201-1211; doi: 10.1242/dmm.020933

    Editor's choice - Drug Discovery Collection: The study describes a rapid in vivo screen for novel strategies to treat pancreatic ductal adenocarcinoma (PDA).

  • RESEARCH ARTICLE
    Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo
    Fariba Poosti, Bao Tung Pham, Dorenda Oosterhuis, Klaas Poelstra, Harry van Goor, Peter Olinga, Jan-Luuk Hillebrands
    Disease Models & Mechanisms 2015 8: 1227-1236; doi: 10.1242/dmm.020172

    Drug Discovery Collection: TGFβ induces renal fibrosis in ex vivo cultured precision-cut kidney slices, which can be attenuated by IFNγ.

  • RESEARCH ARTICLE
    A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models
    Rosamaria Lappano, Camillo Rosano, Assunta Pisano, Maria Francesca Santolla, Ernestina Marianna De Francesco, Paola De Marco, Vincenza Dolce, Marco Ponassi, Lamberto Felli, Grazia Cafeo, Franz Heinrich Kohnke, Sergio Abonante, Marcello Maggiolini
    Disease Models & Mechanisms 2015 8: 1237-1246; doi: 10.1242/dmm.021071

    Drug Discovery Collection: This paper highlights mechanisms through which a calixpyrrole derivative acts as a newly identified selective antagonist of GPER in different model systems.

  • RESEARCH ARTICLE
    Glycolytic inhibitor 2-deoxyglucose simultaneously targets cancer and endothelial cells to suppress neuroblastoma growth in mice
    Chao-Cheng Huang, Shuo-Yu Wang, Li-Ling Lin, Pei-Wen Wang, Ting-Ya Chen, Wen-Ming Hsu, Tsu-Kung Lin, Chia-Wei Liou, Jiin-Haur Chuang
    Disease Models & Mechanisms 2015 8: 1247-1254; doi: 10.1242/dmm.021667

    Drug Discovery Collection: Neuroblastomas are sensitive to treatment with the glycolytic inhibitor 2-deoxyglucose, which can simultaneously target cancer and endothelial cells to suppress tumor growth.

  • RESOURCE ARTICLE
    From drug response profiling to target addiction scoring in cancer cell models
    Bhagwan Yadav, Peddinti Gopalacharyulu, Tea Pemovska, Suleiman A. Khan, Agnieszka Szwajda, Jing Tang, Krister Wennerberg, Tero Aittokallio
    Disease Models & Mechanisms 2015 8: 1255-1264; doi: 10.1242/dmm.021105

    Drug Discovery Collection: The authors take a pan-cancer approach that provides functional insights into molecular vulnerabilities across various cancer subtypes and patient-specific target addiction patterns that could lead to actionable treatment strategies.

  • RESEARCH ARTICLE
    A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosis
    Xiaohua Xu, Aleksandar Denic, Luke R. Jordan, Nathan J. Wittenberg, Arthur E. Warrington, Bharath Wootla, Louisa M. Papke, Laurie J. Zoecklein, Daehan Yoo, Jonah Shaver, Sang-Hyun Oh, Larry R. Pease, Moses Rodriguez
    Disease Models & Mechanisms 2015 8: 831-842; doi: 10.1242/dmm.020727

    Summary: A single peripheral dose of a recombinant natural human IgM increases lifespan and delays neurological deficits in mouse models of human ALS.

  • A MODEL FOR LIFE
    Unravelling proteinopathies: an interview with David Rubinsztein
    Disease Models & Mechanisms 2015 8: 643-646; doi: 10.1242/dmm.021360

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