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Annual Report for Fiscal Year 2018

Annual Report for Fiscal Year 2018
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https://ntp.niehs.nih.gov/go/860582

Tox Challenge – Stage Two Winners Announced

Scientists are using high-speed, automated screening technologies, called high-throughput screening (HTS) assays, to expose living cells or isolated proteins to chemicals. Current HTS assays measure toxicity of the chemicals themselves, but do not test for metabolites, which are altered forms of chemicals produced as the body breaks down the original compound and are sometimes more toxic than the original chemical.

To help capture that missing information, NTP and partners launched the Transform Toxicity Testing Challenge in January 2016. The "Tox Test Challenge" asked teams of scientists to develop techniques to retrofit existing HTS assays to incorporate processes that reflect how the body metabolizes chemicals. After selecting semi-finalists in May 2017, the partners named the five stage two winners on November 1, 2017.

The winners produced practical designs for new technologies that can rapidly test whether some of the thousands of chemicals in use can harm human health:

  • Brian Johnson, Ph.D., Onexio Biosystems, LLC. Johnson created a system that uses the natural metabolic activity of human liver cells to generate chemical metabolites and then deliver these metabolites to existing assays. This Metabolism Integrated Cell RepOrter MicroTiter plate (MICRO MT) system is technically simple and requires little additional equipment.
  • Moo-Yeal Lee, Ph.D., Cleveland State University and Rayton Gerald, Solidus Biosciences. Lee and Gerald developed a 384-well plate that supports three-dimensional cell cultures. It includes an array of human liver cells for both gene expression and high-content toxicity screening.
  • Albert Li, Ph.D., In Vitro ADMET Laboratories (IVAL), LLC. Li developed the MetMax Human Hepatocytes system to serve as an external liver metabolism system. The test chemical is added to allow metabolism by liver cells. Both the parent chemical and its metabolites then migrate across a semi-permeable membrane to interact with the target cells.
  • Lawrence Vernetti, Ph.D., University of Pittsburgh Drug Discovery Institute. Vernetti developed a system to supply rodent or human liver cells for co-culture with a second cell or cell-free assay. It allows both test agents and metabolites to be transferred directly to the test plates.
  • Hongbing Wang, Ph.D., University of Maryland School of Pharmacy. Wang developed a cell culture model that uses a type of cell called human primary hepatocyte. The platform can be scaled up to an HTS format that allows current cell culture-based assays to produce physiologically relevant metabolites.
Toxicity test challenge with microscope