Coordinator: Andre Kleensang (firstname.lastname@example.org)
Human Toxome Project Website (external)
The Human Toxome program aims primarily to support the evolution of toxicology towards a mechanism-based science. CAAT promotes the use of advanced-omics and high-throughput technologies and supports the implementation of knowledge-based frameworks (such as Pathways of Toxicity and Adverse Outcome Pathways) and plays a key role in implementing the NAS Tox21 vision report from 2007. At the moment the
program is mainly driven by two funded projects: The NIH Transformative Research Grant “Mapping the Human Toxome by Systems Toxicology” and the EU-ToxRisk project.
In the last six months CAAT was able to achieve a significant number of goals:
1. Two new published articles from the NIH Transformative Research Grant “Mapping the Human Toxome by Systems Toxicology”:
Kleensang A, et al.: Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function. Nature Scientific Reports 2016, 6:28994
Pendse SM, et al: Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity. Arch Toxicol 2016 (Epub ahead of print)
Since its publication, the paper “Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function” has garnered increasing attention. Some of the recent coverage included Science Daily, Quo, News Medical, FisiClick, and Agilent Inc. The project resulted so far in 13 publications in international peer-reviewed journals which have already been cited more than130 times by other scientists.
2. EU-ToxRisk/Tox21 Workshop Mainz/Germany
CAAT-Europe and US helped to organize and participated in a combined EU-ToxRisk/Tox21 Workshop held in Mainz/Germany in Sept. 2016. The EU-ToxRisk project and the Toxicology in the 21st Century (Tox21) initiative in the US have agreed there to collaborate on efforts to reduce the use of animals and achieve more efficient chemical safety assessments.
The following areas were agreed upon for areas of mutual practical cooperation.
- Develop practices of cross-consortium data sharing with particular emphasis on the ongoing EU-ToxRisk case studies
- Develop core methodology in read-across and the application of high-throughput transcriptomics for safety assessment
- Create synergies across overlapping chemical subsets
- Utilise ongoing developments of in vitro tissue models and computer-based predictions of drug concentrations for risk assessment
- Develop joint case studies focused on innovations in the application of alternative approaches
In March 2017 CAAT US will organize as a satellite meeting to the Society of Toxicology Annual Meeting a follow up EU-ToxRisk/Tox21 meeting which will include as well representatives from US FDA. Tox21 is a federal collaboration among the US Environmental Protection Agency, the National Institutes of Health, including the National Center for Advancing Translational Sciences and the National Toxicology Program at the National Institute of Environmental Health Sciences, and the US Food and Drug Administration.
The EU-ToxRisk project is €30 million EU Horizon 2020 project involing 38 European partners and one—CAAT—from the US. EU-ToxRisk aims at the “development of a new way of risk assessment.” It promotes mechanism-based toxicity testing and risk assessment according to the principles laid down for toxicology for the twenty-first century. The project will
integrate advances in in vitro and in silico toxicology, read-across methods, and adverse outcome pathways.