HESI Insights - May 2022

The United Nations subcommittee on the Globally Harmonized System of Classification and Labelling of Chemicals is examining whether or not to revise it’s definition of a germ cell mutation. Changes to the definition could impact the classification and labeling for many chemicals. HESI’s Genetic Toxicology Technical Committee Germ Cell Working Group is working to support their evaluation by re-visiting existing data regarding a substance’s molecular interaction with germ cell DNA. The working group will provide their opinion on what positive endpoints in somatic tissues and/or level of exposure in gonads would allow classification and labelling as a germ cell mutagen.

View the full Terms of Reference and Work Program.

Learn more about HESI’s Genetic Toxicology Technical Committee.

The HESI  Developmental and Reproductive Toxicology Committee (DART) is launching a trainee program to heighten the awareness of career opportunities with DART and to provide guidance to aspiring toxicologist who like to make an impact on the field.

To learn more about the program please watch this short promotion video and share with your networks. The DART Career Symposium will take place this fall. Stay tune for more detail in the upcoming months. This is an event you don’t want to miss!

Learn more about the HESI Developmental and Reproductive Toxicology Committee (DART)

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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, specifically from formalin-fixed samples. This publication in Nature Scientific Reports describes a study that evaluated whether chemical and heat treatment improves DNA-sequencing data of formalin-fixed samples. Researchers from HESI’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee found that organocatalyst (2-amino-5-methylphenyl phosphonic acid) treatment with extended heat incubation can improve DNA Exosome-sequencing data quality of formalin-fixed paraffin-embedded tissue samples. Implications of these finding have important applications in translational science and precision medicine. With further optimization, conducting genomic analysis on archived tissue samples will be more achievable.

Read the full article here:
Organocatalyst treatment improves variant calling and mutant detection in archival clinical samples.
Leah C. Wehmas, Charles E. Wood, Ping Guan, Mark Gosink & Susan D. Hester. Scientific Reports. 20 April, 2022

Click to learn more about HESI’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee

HESI’s Developmental and Reproductive Toxicology Committee has a new publication in Disease Models & Mechanisms which reviews five common neonatal diseases – bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, perinatal hypoxic–ischemic encephalopathy and neonatal sepsis – and the available in vivo, in vitro and in silico preclinical models for studying these diseases. This review is intended to help guide current and future researchers toward successful development of therapeutics in these areas of high unmet medical need.

Read the full article here:
The benefits, limitations and opportunities of preclinical models for neonatal drug development. Champion et. al. Disease Models & Mechanisms. 25 April 2022

Click to learn more about HESI’s Developmental and Reproductive Toxicology (DART) Committee

HESI’s Genetic Toxicology Technical Committee (GTTC) aims to enhance the use of mechanistic information in genotoxicity assessment by building empirical support for the relationship between molecular initiating events and regulatory endpoints in genetic toxicology with the development of several adverse outcome pathways (AOPs): oxidative stress, tubulin binding, topoisomerase II and aurora kinase. The GTTC’s first adverse outcome pathway (AOP) describing modes of actions leading to potentially heritable genomic damage was recently published in Environmental and Molecular Mutagenesis. This AOP focused on oxidative DNA damage and resulting mutations and chromosomal aberrations. This AOP is currently included in the OECD workplan and is awaiting approval and endorsement. For additional information, please contact Connie Chen (cchen@hesiglobal.org).

Read the full article:
AOP report: Development of an adverse outcome pathway for oxidative DNA damage leading to mutations and chromosomal aberrations. Eunnara Cho, Ashley Allemang, Marc Audebert, Vinita Chauhan, Stephen Dertinger, Giel Hendriks, Mirjam Luijten, Francesco Marchetti, Sheroy Minocherhomji, Stefan Pfuhler, Daniel J. Roberts, Kristina Trenz, Carole L. Yauk. Environmental and Molecular Mutagenesis. 21 March 2022.

Click to learn more about HESI’s Genetic Toxicology Technical Committee (GTTC)

HESI’ Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee hosted a webinar on 10 May 2022 where Dr. Subham Dasgupta presented on the project titled, Phenotypically Anchored mRNA & miRNA Expression Profiling in Zebrafish Reveals Flame Retardant Chemical Toxicity Networks. Click for full details including Bio & Abstract.

Click here to view the recording

The recent ITC Spring Business Meeting (April 26-27) featured 3 talks on Immunogenicity ( Food, Biologics and Cell/ Gene Therapies). Our special guest speakers included Dr. Antonella Cianferoni MD/PhD (PATB) , Dr. Phillipp Kolb (Institute of Virology) and Dr. Hui Ling MD/PhD (CT-TRACS). Modeling strength in convening expert scientists to address current needs with the scientific community, the ITC wanted to leverage the expertise of our sister committee to discuss a persistent topic in recent years, immunogenicity. Through an exchange of knowledge and ideas, we hope to find ways to synergize our efforts in this area to make a valuable contribution to this area of research.

Learn more about the Immuno-Safety Committee (ITC)

The Botanical Safety Consortium presented at the 2022 Society of Toxicology meeting, which was held virtually and in person in San Diego, CA March 27-31, 2022. The presented posters highlighted the work of some of the technical working groups. Click poster titles to view each poster.

• Application of In Silico and In Vitro Approaches for Evaluating Developmental and Reproductive Toxicity in Botanical Products
• Physiologically based pharmacokinetic (PBPK) simulations and modeling of botanical constituents
• A Strategy for Developing a Framework of Genotoxicity Assays for Safety Assessment of Botanicals
• In Silico Prediction of Botanical Constituents’ Metabolites

Click to learn more about the Botanical Safety Consortium

HESI’s Cell Therapy – TRAcking, Circulation, & Safety Committee’s Point of Administration-Biodistribution Working Group presented at the International Society for Cell and Gene Therapies’ annual meeting, held in-person in San Francisco, CA, May 4-7, 2022. The poster entitled “Imaging cellular therapeutics in vivo for safety and efficacy: perspectives and a new resource from the multi-stakeholder committee HESI CT-TRACS” highlighted learnings from the working group interactions and committee publication (Helfer et al. 2021) and announced the upcoming “Data Portal for Imaging Cell Therapies” or DPICT, a new online resource developed by the committee to address a need expressed by the cell therapy community. DPICT (currently in pre-launch phase) is a searchable online central repository of clinical studies including in vivo cell-tracking methodologies to evaluate the biodistribution and fate of the therapeutic cells after administration. The ISCT 2022 meeting was attended by >1,650 in person participants.

Click to learn more about Cell Therapy – TRAcking, Circulation, & Safety Committee (CT-TRACS)

Save the Date! The following are internal meetings:

May 16-17, 2022 – GTTC Annual Meeting (Hybrid)

May 19-20, 2022 – CT-TRACS Spring Business Meeting (Hybrid)

The HESI Cardiac Safety Committee is please to announce the last webinar in their Early Career Seminar Award Series. This competitive award is given to postdoctoral or early career scientists who have compelling research related to cardiovascular safety and risk assessment, and the webinar series offers an opportunity for awardees to share their research, learn from, and network with experts at HESI. The webinar will feature the work of Dr. Shagun Krishna, NTP-NIEHS,  and is scheduled for 12 May 2022 at 10:00 am ET.

Registration is free, contact for details: HESI Cardiac Safety cardiacsafety@hesiglobal.org

HESI’s Next Generation Ecological Risk Assessment Committee will be in attendance at SETAC Europe 15-19 May 2022.

Connie Mitchell will be there to give a platform presentation entitled “Investigating endocrine-disrupting properties of chemicals: developments and challenges towards new approach methodologies (NAMs).”

HESI’s Connie Mitchell will be presenting at the 21st International Symposium on Pollutant Responses in Marine Organisms (PRIMO21). Her talk is titled “The EnviroTox database and application tools: Leveraging existing data to meet chemical risk assessment needs“.

For information about the conference see the PRIMO21 website.

May 25, 2022

The Cell Therapy – TRAcking, Circulation & Safety (CT-TRACS) Committee will present preliminary results of their pilot project “New approaches for identification of potential off-target mutations associated with CRISPR genome editing in cell therapies” at the Advanced Therapies 2022 Congress, London, UK, as part of Track #7: “Innovation” (oral presentation scheduled for 12 pm on 25 May 2022).

Dr. Paolo Boffetta of Stony Brook University will present a talk titled “Evidence integration in epidemiology and risk assessment” at the upcoming webinar series, hosted by HESI’s Environmental Epidemiology Committee.

Abstract: Hazard identification and risk assessment are based on integration of human data, primarily coming from epidemiology and clinical studies, with experimental and mechanistic studies. I will review three approaches aimed at integrating different lines of evidence: the IARC Monographs program (hazard identification for carcinogens), the Epi-Tox framework (hazard identification) and the Venice criteria (genetic risk factors), addressing their strengths and limitations, and will discuss how data integration can be applied to risk assessment.

Bio: Dr. Boffetta is a Professor in the Department of Family, Population & Preventive Medicine at Stony Brook University and Associate Director for Population Sciences at Stony Brook Cancer Center. He graduated in Medicine from the University of Turin and obtained a Master in Public Health from Columbia University. He worked at the American Cancer Society in New York, the International Agency for Research on Cancer (World Health Organization) in Lyon, France, the German Cancer Research Center in Heidelberg, Germany, and the Icahn School of Medicine at Mount Sinai in New York. He is a Professor at the University of Bologna, Italy and holds adjunct professorship at several other universities, including Harvard and Vanderbilt. His main fields of research are cancer epidemiology and cancer prevention, with emphasis on global oncology, environmental exposures, personal behaviors, gene-environment interactions, molecular epidemiology and evidence integration. He has established and coordinated international consortia in cancer epidemiology and prevention, including ILCCO (lung cancer), INHANCE (head and neck cancer), PANC4 (pancreatic cancer), ACC (Asia Cohort Consortium), StoP (stomach cancer), and ILCEC (liver cancer).

Click Here to Register

HESI is among 30+ international organizations and companies supporting a series of annual Microphysiological systems (MPS) World Summits to present the latest scientific achievements, discuss the advances and challenges, and enable communication between young and newly interested scientists and pioneers of the MPS field.

HESI’s mission aligns with the proposed goal of the MPS World Summit of planning a series of global conferences on microphysiological systems towards bringing all stakeholders together from across sectors and career stages to promote the development and application of this technology, to facilitate its expanded scientific and regulatory use.

Please see the 2022 Summit event page for more details (https://mpsworldsummit.com/session/hybrid-conference/).

The Summit will be a hybrid event, held May 30^th-June 3^rd, 2022. For questions about the initiative, feel free to reach out to HESI’s contact point: Lucilia Mouriès (lmouries@hesiglobal.org).

A number of HESI committees will be presenting posters at the EFSA One 2022 conference.

Committee Posters

Animal Alternatives in Environmental Risk Assessment Committee

• New Approach Methodologies (NAMs) for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians (virtual poster)

Comprehensive Protein Allergen Resource

• The COMPARE Database: A Comprehensive Public Resource for Allergen Identification and Protein Allergenicity Assessment (presented in person by Lars Poulsen)

Transforming the Evaluation of Agrochemicals (TEA) Committee

• Transforming the Evaluation of Agrochemicals (presented in person by Marco Corvao)

For more information see the ONE 2022 website.

SaveTheDate! Don’t miss the 2022 HESI Annual meeting on June 8-9, 2022. Online and In Person meeting options available!

Meeting Sessions include:

• HESI and Global Partnerships for Good in 2022
• HESI Science at the Cutting Edge: Evolving Applications of Error Corrected Sequencing in HESI Scientific Programs
• HESI THRIVE – A HESI Competitive Seed Grant Program to Advance Quality of Life for Cancer Patients and Survivors
• Science Foresight: Forward Science Session Focus on Artificial Intelligence

Click here for the detailed agenda and to register!

Call for Applicants! Are you thinking about doing your PhD? If you have a degree in bioengineering or biological sciences you should apply by May 13, 2022 for this fully-funded opportunity to work in a world-renowned lab (http://ow.ly/9x0550IMRc2) in partnership with Newcastle University and the Health and Environmental Sciences Institute (HESI) Cell Therapy – TRAcking, Circulation & Safety Committee.

3 year PhD Studentship to study “Improved understanding of cell fate with multi-visceral normothermic perfusion models.”

Click to learn more -> https://lnkd.in/dnmUC6j4

Spring is slowly coming to New England! The June 8-9th Annual meeting should greet us with wonderful weather in Washington DC. The Annual meeting will mark the end of my term as HESI President of the Assembly. I have thoroughly enjoyed working with the HESI staff, Executive Committee, and Board to guide HESI through this difficult time and meet our strategic initiatives and mission. When Martin van den Berg (HESI Chair of the Board) and I began our terms, two Board Strategic Initiatives had been launched. This annual meeting highlights some of the fruits of these labors with the first report on the Global Risk Assessment Training Center (GRATC) from the Global Outreach Initiative and the awarding of the first HESI Innovation Prize Lecture (Dr. Kenneth Olden, retired NIEHS) from the Academic Outreach Initiative. The annual meeting will also highlight how Artificial Intelligence, one of the Science Foresight topic areas, offers the ability to reduce animal usage and improve the safety of agricultural products. Martin and I will be transitioning our roles at the June meeting so please do welcome and congratulate Ruth Roberts (Apconix) who will assume Chair of the Board and Anthony Holmes (NC3Rs) who will assume President of the Assembly.

As always, thank you for your contributions to advancing HESI’s Mission – we have thrived during this difficult time due to your dedication and ingenuity! It has been an honor serving you!

Best regards,

Jon C. Cook, PhD, ABT, DABT
HESI President of Assembly