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人类肾毒性的高通量预测

High-throughput prediction of nephrotoxicity in humans.

作者信息

Loo Lit-Hsin, Zink Daniele

机构信息

Bioinformatics Institute (BII), Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Institute of Bioengineering and Nanotechnology (IBN), Singapore.

出版信息

Altern Lab Anim. 2017 Nov;45(5):241-252. doi: 10.1177/026119291704500506.

DOI:10.1177/026119291704500506
PMID:29112452
Abstract

The Lush Science Prize 2016 was awarded to Daniele Zink and Lit-Hsin Loo for the interdisciplinary and collaborative work between their research groups in developing alternative methods for the prediction of nephrotoxicity in humans. The collaboration has led to the establishment of a series of pioneering alternative methods for nephrotoxicity prediction, which includes: predictive gene expression markers based on pro-inflammatory responses; predictive in vitro cellular models based on pluripotent stem cell-derived proximal tubular-like cells; and predictive cellular phenotypic markers based on chromatin and cytoskeletal changes. A high-throughput method was established for chemical testing, which is currently being used to predict the potential human nephrotoxicity of ToxCast compounds in collaboration with the US Environmental Protection Agency. Similar high-throughput imaging-based methodologies are currently being developed and adapted by the Zink and Loo groups, to include other human organs and cell types. The ultimate goal is to develop a portfolio of methods accepted for the accurate prediction of human organ-specific toxicity and the consequent replacement of animal experiments.

摘要

2016年的鲁什科学奖授予了达尼埃莱·津克和卢立欣,以表彰他们研究团队之间的跨学科合作,该合作致力于开发预测人类肾毒性的替代方法。这项合作促成了一系列开创性的肾毒性预测替代方法的建立,其中包括:基于促炎反应的预测性基因表达标志物;基于多能干细胞衍生的近端肾小管样细胞的预测性体外细胞模型;以及基于染色质和细胞骨架变化的预测性细胞表型标志物。还建立了一种用于化学测试的高通量方法,目前正与美国环境保护局合作,用于预测ToxCast化合物对人类的潜在肾毒性。津克和卢立欣团队目前正在开发和应用类似的基于高通量成像的方法,以涵盖其他人体器官和细胞类型。最终目标是开发一套被认可的方法,用于准确预测人体器官特异性毒性,从而取代动物实验。

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