Rapid and accurate high-throughput in vitro prediction of nephrotoxicity in humans with ProxTox-HTS

Date: March 01 2018
Presenter(s): Dr Daniele Zink

Speaker: Daniele Zink, PhD, Team Leader and Principal Research Scientist, IBN Singapore

Time:

7:00 am (PDT)

10:00 am (EST)

3:00 pm (GMT)

4:00 pm (CET)

5:00 pm (IST)

12:00 pm (Tokyo, Seoul)

Summary:

The human kidney can be damaged by a wide range of xenobiotics, such as industrial chemicals, environmental toxicants and drugs. Major targets for compound-induced damage are renal proximal tubule cells (PTCs) due to their role in compound transport, metabolism and clearance. ProxTox-HTS is the first high- throughput in vitro screening method developed to predict nephrotoxicity in humans with high accuracy. The HTS platform was developed without using pre-defined endpoints, instead, predictive cellular changes were identified by phenotypic profiling after compound treatment. Analysis of 129 cellular features was conducted by powerful high content imaging and their changes were compared by machine learning to the known clinical effects of the compounds on human kidneys. It has been pre-validated with 44 chemically diverse compounds, with well-characterized effects. The method utilizes primary human renal proximal tubule or HK-2 cells in 384-well format, the test balanced accuracies are 82% (primary PTCs) and 89% (HK-2 cells), respectively. These data were obtained using relatively short compound exposure, and  also included compounds that typically lead to chronic kidney injury gave positive results. ProxTox-HTS can therefore be used for the identification of acutely as well as chronically nephrotoxic compounds.

ProxTox-HTS a new tool for in vitro high-throughput nephrotoxicity prediction.

Speaker's Bio:

Daniele Zink studied Biology at the University of Bielefeld (Germany) and earned her PhD from the University of Heidelberg in 1995 where she worked in the fields of developmental biology and epigenetics. After becoming a postdoctoral fellow at the Institute of Human Genetics of the University of Heidelberg, she was appointed in 1996 as Research Assistant Professor at the Institute of Anthropology and Human Genetics of the Ludwig-Maximilians University (LMU) of Munich, Germany, where she completed her Habilitation in Cell Biology in 2001. In 2001, she was awarded a grant from the Volkswagen-Foundation for the funding of a Junior Group. She was head of the Junior Group located at the LMU (Department of Biology II) until she moved to the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research, Singapore in 2007, as Team Leader and Principal Research Scientist. Her research at IBN focuses on the development of predictive models for in vitro toxicology/nanotoxicology. In addition, she performs research on stem cells, which is directed towards applications in predictive toxicology and the development of cost-effective fully synthetic cultivation systems for industrial applications. The work on predictive in vitro models has been awarded by the US Society of Toxicology and has won the prestigious LUSH Prize (2016, Science Category). The predictive in vitro models are used in collaboration with the US Environmental Protection Agency for the prediction of the human nephrotoxicity of ToxCast compounds. Zink holds 12 patents/patent applications, is Editorial Board Member of Scientific Reports and has > 70 publications, which include publications in Nature, Nature Reviews Cancer, Archives of Toxicology and Nanotoxicology.