This event was organized by the HESI Genomics Committee.
Results of 2005-2007 Research Programs and Next Steps: A Public Workshop
November 7, 2007 – November 8, 2007
Washington, DC, USA
The mission of HESI’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee is to develop and deliver innovative systems toxicology approaches for risk assessment. The committee aims to catalyze adoption of new translational and predictive tools that guide decision-making based on mechanistic understanding of toxicological response.
The HESI eSTAR committee is proud to announce that it was awarded a $250,000 USD grant (U01) as part of the USFDA’s Biomarker Qualification Program in June 2022. This funding will be partnered with Committee resources to support a four-site ring trial generating additional data on the TGx-DDI (TGx = toxicogenomics; DDI = DNA damage inducing) biomarker. The TgX-DDI biomarker is currently under review by the FDA as part of the FDA Biomarker Qualification program. Pending the results of this final study, the marker is anticipated to gain FDA approval for optional use as added weight of evidence in the assessment of genotoxicity. The marker has the potential to improve upon the low specificity of in vitro chromosome damage assays used in current testing and to aid drug development by providing mechanistic insights into transcriptional changes occurring in genes involved in key DNA damage pathways.
The Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee is exploring two new projects, one relating to cell painting for safety assessment and the other exploring the use of error corrected sequencing to predict tumorigenicity from non-genotoxic carcinogens. Both groups are looking for additional stakeholders.
Interested in finding out more? Please contact Saddef Haq (shaq@hesiglobal.org)
This group is exploring the use of transcriptomic point of departure for chemical risk assessment. A state of the science manuscript is in preparation.
Three active working groups have compiled, curated, and begun analysis of transcriptomic, toxicologic, and pathologic data to identify short-term transcriptional signatures. These signatures will inform molecular mechanisms underlying pathogenesis of histologic risk factors of neoplasia observed in 90-day studies or chronic 6-month rat toxicology studies and that will inform the value/need to conduct a 2-year rat carcinogenicity study. Novel data housing/analysis partnerships were formed with the NIEHS Chemical Effects in Biological Systems (CEBS) data repository and Lhasa.
An miRNA best practices manuscript was submitted in August 2020. A second paper on renal miRNA biomarkers will be submitted by October 2020. A new experimental and/ or methodology project to reduce hurdles to the use of miRNAs for translational safety assessment and in biological discovery efforts is in development.
The HESI eSTAR committee is proud to announce that it was awarded a $250,000 USD grant (U01) as part of the USFDA’s Biomarker Qualification Program in June 2022. This funding will be partnered with Committee resources to support a four-site ring trial generating additional data on the TGx-DDI (TGx = toxicogenomics; DDI = DNA damage inducing) biomarker. The TgX-DDI biomarker is currently under review by the FDA as part of the FDA Biomarker Qualification program. Pending the results of this final study, the marker is anticipated to gain FDA approval for optional use as added weight of evidence in the assessment of genotoxicity. The marker has the potential to improve upon the low specificity of in vitro chromosome damage assays used in current testing and to aid drug development by providing mechanistic insights into transcriptional changes occurring in genes involved in key DNA damage pathways.
Learn more about the use of the TGx-DDI transcriptomic biomarker for the genotoxicity assessment of data-poor chemicals here (poster presented at the 2021 EMGS Virtual Annual Meeting by Anne-Marie Fortin, University of Ottawa).
US Environmental Protection Agency
GlaxoSmithKline
November 7, 2007 – November 8, 2007
Washington, DC, USA
This event was organized by the HESI Genomics Committee.
Toxicological Sciences, 2022
This call-to-action paper published in Toxicological Sciences describes a multi-sector collaboration seeking to accelerate the evaluation of biomarker tools in carcinogenicity studies which will facilitate the transition from current heavy reliance on conventional 2-year rodent ...
Nature Scientific Reports, 2022
Most archived biological tissue samples are preserved in formalin. Formalin fixation of biological samples damages nucleic acids and limits their use in future genomic analyses. Improved tools are needed to increase nucleic acid yield, reduce artifacts, and facilitate analysis and interpretation of genomic data, ...
Critical Reviews in Toxicology, 2021
MicroRNAs (miRNAs) are small non-coding RNA that regulate the expression of messenger RNA and are implicated in almost all cellular processes. Importantly, miRNAs can be released extracellularly and are stable in these matrices where they may serve as indicators of organ or cell-specific toxicity, disease, and biological ...
Toxicological Sciences, 2020
Drug-induced kidney injury (DIKI) is a major concern in both drug development and clinical practice. There is an unmet need for biomarkers of glomerular damage and more distal renal injury in the loop of Henle and the collecting duct (CD). A cross-laboratory program to identify and characterize urinary microRNA (miRNA) patterns ...
Regulatory Toxicology and Pharmacology, 2019
Robust genomic approaches are now available to realize improvements in efficiencies and translational relevance of cancer risk assessments for drugs and chemicals. The authors propose a path for implementation of innovative cancer risk assessment including incorporating genomic signatures to assess mechanistic relevance ...
Frontiers in Big Data, 2019
Genotoxicity testing is an essential component of the safety assessment paradigm required by regulatory agencies world-wide for analysis of drug candidates, and environmental and industrial chemicals. Current genotoxicity testing batteries feature a high incidence of irrelevant positive findings – particularly for in ...
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