eSTAR

Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee

Mission Statement

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.

Working Groups

  • Carcinogenomics Project

    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.

  • Cell Painting - Oasis Consortium

    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.

  • Error Corrected Sequencing

    This newly formed group is exploring the use of error corrected sequencing to detect clonal expansion of non-genotoxic carcinogens.

  • FFPE Project

    A manuscript on DNA de-modification analysis of clinical tumor samples was accepted; the project will sunset after an educational webinar.

  • miRNA Biomarkers Project

    Designed and launched a multi-site experimental program on the use of exosomal miRNAs expressed in response to renal toxicants.

  • TGx-DDI Project

    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).

  • Use of Transcriptomic Point of Departure (POD) for Chemical Risk Assessments

    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.

Recent Highlights

 

HESI OASIS Consortium receives $1.2 million USD grant

The OASIS Consortium, a working group within HESI’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee, received $1.2 million from the Massachusetts Life Sciences Center Bytes to Bytes Awards. These funds, supplemented with $2.5 from industry, will support laboratory work at the Broad Institute of Harvard and MIT to investigate Cell Painting, transcriptomics, and proteomics for decision making in toxicology. These funds also support two postdocs positions at the Broad Institute. This 3-year project will explore approximately 1600 compounds across 3 cell types, organoids, and microphysiological systems.

Read the full press release here.

 

TGx-DDI Project receives FDA Funding

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.

Committee Publications

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A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies

Toxicological Sciences, 2022

J. Christopher Corton, Constance A. Mitchell, Scott Auerbach, ...

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 ...

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Organocatalyst treatment improves variant calling and mutant detection in archival clinical samples

Nature Scientific Reports, 2022

Leah C. Wehmas, Charles E. Wood, Ping Guan, ...

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, ...

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Methodological Considerations for Measuring Biofluid-Based MicroRNA Biomarkers

Critical Reviews in Toxicology, 2021

Chorley BN, Atabakhsh E, Doran G, Gautier JC, ...

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 ...

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Committee Resources

HESI Staff

Leadership Team

  • Deidre Dalmas Wilk, PhD

    GlaxoSmithKline

  • Scott Auerbach, PhD

    National Institute of Environmental Health Sciences

  • John Rooney, PhD

    Syngenta

Committee Events

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eSTAR Committee Annual Meeting 2022

November 3, 2022 – November 4, 2022

eSTAR Committee Annual Meeting, Virtual

The goals of the eSTAR Annual Meeting will be to communicate updates from the various working groups and listen to talks from leading experts in systems toxicology. On the second day we will have two concurrent half-day sessions for our newest projects, Error Correcting Sequencing and Cell Painting. The entire meeting is free and ...

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HESI at ICEM2022

August 27, 2022 – September 1, 2022

Ottawa, Canada

HESI will be attending the 13th International Conference on Environmental Mutagens. Meet us there!

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2022 SOT Annual Meeting

March 27, 2022 – March 31, 2022

San Diego, CA, USA

A number of HESI Scientific Committees will be presenting at the upcoming Society of Toxicology meeting, which will be held virtually and in person in San Diego, CA March 27-31, 2022.

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            [primary_table] => wp_posts
            [primary_id_column] => ID
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                    [1] => mt1
                    [2] => mt2
                    [3] => mt3
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                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_postmeta
                            [cast] => CHAR
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                            [key] => _ilsi_date
                            [value] => 2050-01-01
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                            [compare_key] => =
                            [alias] => mt1
                            [cast] => CHAR
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                            [value] => 2050-01-01
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                            [compare_key] => =
                            [alias] => mt2
                            [cast] => CHAR
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                    [mt3] => Array
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                            [key] => _ilsi_date
                            [value] => Array
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                                    [0] => 2022-01-01
                                    [1] => 2022-12-31
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                            [compare] => BETWEEN
                            [compare_key] => =
                            [alias] => mt3
                            [cast] => CHAR
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                    [mt4] => Array
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                            [value] => 2022-12-31
                            [compare] => <
                            [compare_key] => =
                            [alias] => mt4
                            [cast] => CHAR
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                )

            [has_or_relation:protected] => 
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    [date_query] => 
    [request] => 
					SELECT SQL_CALC_FOUND_ROWS  wp_posts.ID
					FROM wp_posts  LEFT JOIN wp_term_relationships ON (wp_posts.ID = wp_term_relationships.object_id) INNER JOIN wp_postmeta ON ( wp_posts.ID = wp_postmeta.post_id )  INNER JOIN wp_postmeta AS mt1 ON ( wp_posts.ID = mt1.post_id )  INNER JOIN wp_postmeta AS mt2 ON ( wp_posts.ID = mt2.post_id )  INNER JOIN wp_postmeta AS mt3 ON ( wp_posts.ID = mt3.post_id )  INNER JOIN wp_postmeta AS mt4 ON ( wp_posts.ID = mt4.post_id )
					WHERE 1=1  AND ( 
  wp_term_relationships.term_taxonomy_id IN (143)
) AND ( 
  wp_postmeta.meta_key = '_ilsi_date' 
  AND 
  ( 
    ( mt1.meta_key = '_ilsi_date' AND mt1.meta_value <= '2050-01-01' ) 
    AND 
    ( mt2.meta_key = '_ilsi_end_date' AND mt2.meta_value <= '2050-01-01' ) 
    AND 
    ( mt3.meta_key = '_ilsi_date' AND mt3.meta_value BETWEEN '2022-01-01' AND '2022-12-31' ) 
    AND 
    ( mt4.meta_key = '_ilsi_date' AND mt4.meta_value < '2022-12-31' )
  )
) AND ((wp_posts.post_type = 'event' AND (wp_posts.post_status = 'publish' OR wp_posts.post_status = 'acf-disabled')))
					GROUP BY wp_posts.ID
					ORDER BY wp_postmeta.meta_value DESC
					LIMIT 0, 6
				
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                    [post_date] => 2022-09-28 19:37:56
                    [post_date_gmt] => 2022-09-28 19:37:56
                    [post_content] => 
                    [post_title] => eSTAR Committee Annual Meeting 2022
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => estar-annual-meeting-2022
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                    [pinged] => 
                    [post_modified] => 2022-11-10 15:17:21
                    [post_modified_gmt] => 2022-11-10 15:17:21
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=event&p=25886
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                    [post_type] => event
                    [post_mime_type] => 
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            [1] => WP_Post Object
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                    [post_date] => 2022-07-19 13:36:39
                    [post_date_gmt] => 2022-07-19 13:36:39
                    [post_content] => 
                    [post_title] => HESI at ICEM2022
                    [post_excerpt] => 
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                    [post_password] => 
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                    [post_date] => 2022-05-02 13:32:55
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                    [post_content] => 
                    [post_title] => Phenotypically Anchored mRNA & miRNA Expression Profiling in Zebrafish Reveals Flame Retardant Chemical Toxicity Networks
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                    [post_date] => 2022-01-10 14:38:42
                    [post_date_gmt] => 2022-01-10 14:38:42
                    [post_content] => 
                    [post_title] => 2022 SOT Annual Meeting
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                    [post_name] => 2022-sot-annual-meeting
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                    [post_date] => 2022-03-08 14:17:12
                    [post_date_gmt] => 2022-03-08 14:17:12
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                    [post_title] => eSTAR Webinar: Tox-GAN: An AI Approach Alternative to Animal Studies – a Case Study with Toxicogenomics
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Contact Us

Health and Environmental Sciences Institute (HESI)

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Phone: +1-202-659-8404
Fax: +1-202-659-8403

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