This study from the HESI eSTAR miRNA Working Group is aimed to find biomarkers that can predict kidney damage.
Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis
Regulatory Toxicology and Pharmacology, 2024
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.
A manuscript was accepted describing the group’s strategy to create transcriptomic biomarkers for particular pathways leading to rat tumors. Current work is to derive and refine the biomarkers. There is also planned experimental work to see gene expression difference in wild type and knock out rats in response to reference compounds.
This newly formed group is planning a proof of concept study to see if Cell Painting data (with or without transcriptomic data) can be predictive of existing rat liver data.
This newly formed group is exploring the use of error corrected sequencing to detect clonal expansion of non-genotoxic carcinogens.
A manuscript on DNA de-modification analysis of clinical tumor samples was accepted; the project will sunset after an educational webinar.
Designed and launched a multi-site experimental program on the use of exosomal miRNAs expressed in response to renal toxicants.
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).
This Working Group has compiled a broad membership of experts across sectors and chemical classes to write a recently accepted manuscript on the state of the science on the use and potential applications of transcriptomic PODs. Future work will include discussion of bioinformatic methods to derive transcriptomic PODs.
Regulatory Toxicology and Pharmacology, 2024
This study from the HESI eSTAR miRNA Working Group is aimed to find biomarkers that can predict kidney damage.
Toxicological Sciences, 2022
Here, a logic framework is proposed to explore the feasibility and future development of transcriptomic methods to refine and replace the current apical endpoint-based regulatory toxicity testing paradigm.
Frontiers in Toxicology, 2022
This case study demonstrates the utility of combining the TGx-DDI biomarker and CometChip® to resolve conflicting genotoxicity data and provides further ...
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 ...
Director, Center for Patient and Consumer Safety (CPCS)
spettit@hesiglobal.orgGlaxoSmithKline
National Institute of Environmental Health Sciences
Syngenta
November 18, 2013
Washington, District of Columbia, USA
The HESI eSTAR Committee hosted a workshop on epigenetics and its potential implication for toxicology.
September 2, 2013 – September 4, 2013
Interlaken, Switzerland
HESI gave several presentations at Eurotox 2013.
May 16, 2013 – May 17, 2013
Paris, France
This workshop was held on 16-17 May 2013 at OECD Congress Center in Paris, France, with the goal to review progress in human carcinogenesis safety evaluation strategies and cancer risk assessment.
hesi@hesiglobal.org
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Fax: +1-202-659-8403
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