HESI Insights March 2025

The HESI Emerging Systems for the Assessment of Risk (eSTAR) Committee has reached a major milestone in advancing drug development tools: the TGx-DDI biomarker has officially been submitted to the FDA’s Center for Drug Evaluation and Research (CDER) Biomarker Qualification Program.

TGx-DDI (Toxicogenomics DNA Damage-Inducing) is a transcriptomic-based biomarker that provides a powerful, mechanistically informed alternative to traditional genotoxicity assays, such as the micronucleus test. These legacy assays are known for their low specificity, leading to inconclusive or overly conservative results that can hinder decision-making. TGx-DDI offers a more accurate readout of DNA damage response pathways using gene expression profiling—representing a leap forward in applying new approach methodologies (NAMs) to risk assessment.

This submission, if accepted, will mark the first biomarker qualified through CDER’s Biomarker Qualification Program—a landmark moment that reflects HESI’s leadership in shaping regulatory science. The qualification of TGx-DDI could help streamline drug development by providing more reliable safety data early in the pipeline, reducing unnecessary in vivo testing, and enhancing human relevance.

This work exemplifies HESI’s mission to deliver collaborative, science-based solutions to complex human and environmental health challenges. Stay tuned for updates as the TGx-DDI biomarker progresses through the FDA’s review process.

We are proud to share that HESI’s Nitrosamines Research Program has been prominently recognized in the FDA Center for Drug Evaluation and Research (CDER) Drug Safety Priorities Fiscal Year 2024 Report, released in February 2025.

The report acknowledges the critical role of FDA nitrosamine experts in supporting research conducted through the FDA/HESI Research Roadmap Planning on Hazard and Risk Assessment of Nitrosamine Impurities in Drugs. This collaboration has been instrumental in advancing strategies to detect, mitigate, and assess the risks associated with nitrosamine impurities—substances that can form in pharmaceuticals and may pose a carcinogenic risk at high exposure levels.

The recognition underscores the impact of HESI’s multi-sector, science-forward approach to addressing urgent drug safety challenges. Nitrosamines were mentioned 19 times throughout the report, emphasizing the topic’s centrality in FDA’s drug quality and safety agenda—and the relevance of the research collaborations spearheaded by HESI.

Through our Nitrosamines Research Program, HESI brings together scientists from academia, regulatory agencies, industry, and NGOs to develop robust, science-based solutions for improving drug safety worldwide. The joint research and roadmap planning have supported the development of analytical tools, novel risk assessment strategies, and data to inform regulatory decision-making.

This recognition reinforces HESI’s mission to collaboratively resolve global health and environmental challenges—and our commitment to translating cutting-edge science into actionable guidance that protects public health.

Read the full FDA report here: FDA Drug Safety Priorities FY24

The HESI Cell Therapy-TRAcking, Circulation, & Safety (CT-TRACS) Committee’s first international multi-site study is helping catalyze the development of a new standard in cell therapy quality control. This collaborative research, recently published in Regenerative Medicine (Watanabe et al., 2023), demonstrated the reproducibility of digital droplet PCR (ddPCR) to sensitively detect residual undifferentiated pluripotent stem cells in iPSC-derived therapy products. Residual pluripotent cells are a potential safety concern in regenerative medicine, and reliable tools are essential for minimizing tumorigenicity risk.

Building on these findings, the Standards Coordinating Body (SCB) has launched a feasibility assessment to explore the creation of a formal standard for evaluating outcomes of iPSC differentiation using ddPCR, based on the experience and knowledge generated from CT-TRACS’s study. Experts from across sectors—including industry, academia, regulatory agencies and standards development organizations—have been convened to guide this effort and assess technical viability, implementation feasibility, as well as relevance to stakeholders and users.

This initiative underscores HESI’s commitment to advancing science-based solutions that enable safe and effective translation of innovative therapies. By proactively identifying challenges and contributing validated tools, the CT-TRACS Committee continues to generate scientific knowledge needed to support the development of harmonized safety practices and international standards development in the rapidly evolving field of cell and gene therapy.

Learn more about the study: Read the full article

We are proud to celebrate Dr. Carole Yauk, HESI’s Chair of the Board and Professor at the University of Ottawa, for receiving the prestigious Alexander Hollander Award from the Environmental Mutagenesis and Genomics Society (EMGS). This award recognizes Dr. Yauk’s exceptional contributions to the fields of environmental mutagenesis and genomics, particularly her groundbreaking work on how environmental pollutants impact human health.

With an extensive research portfolio that bridges science and policy, Dr. Yauk is internationally recognized for her leadership in advancing genomic tools for environmental risk assessment. She is also a champion for inclusivity and mentorship in STEM — qualities that deeply resonate with HESI’s values.

In the words of HESI Executive Director, Dr. Syril Pettit:
“Those of us who are lucky enough to know and work with Carole know she makes every program more effective, more equitable, more rigorous, more collaborative, and more fun.”

Dr. Yauk’s leadership continues to shape HESI’s mission to advance collaborative, science-based solutions for a safer, more sustainable world. We are honored to have her guiding our organization.

Read the full feature on Dr. Yauk’s award and advocacy in science from the University of Ottawa: Click here

Please join us in congratulating Dr. Yauk on this well-deserved recognition!

HESI proudly congratulates Dr. Robyn Leigh Tanguay of Oregon State University on receiving the 2025 Society of Toxicology (SOT) Leading Edge in Basic Science Award.

This prestigious honor recognizes a recent, field-shaping contribution to understanding mechanisms of toxicity. The award highlights pioneering work in mechanistic and predictive toxicology, including the innovative use of zebrafish models to assess complex chemical classes such as PFAS.

Contributions to the field and to collaborative scientific advancement continue to exemplify the spirit of the HESI mission. We are honored to have Dr. Tanguay as a HESI member and celebrate this well-deserved recognition.

To learn more, visit the full announcement on LinkedIn.

Congratulations, Dr. Tanguay!

As the scientific community continues to explore new platforms for connection and collaboration, HESI is expanding its digital footprint. A recent Nature article reported that researchers are increasingly turning to BlueSky as a space to share ideas and engage with peers.
In support of our mission to foster collaborative science for a safer, more sustainable world, HESI is now on BlueSky—a decentralized social media platform gaining momentum in the scientific community.

We’re excited to use this platform to enhance digital engagement with our global scientific community, share timely updates, amplify scientific insights, and connect with a broader audience.

Follow us and join the conversation: hesiglobal.bsky.social

Join the Health and Environmental Sciences Institute (HESI) for a dynamic two-day conference on AI and machine learning‘s impact on drug, chemical, and food safety. Dive into cutting-edge insights, explore challenges, and shape the future of human and environmental health protection.

What to Expect:

Real-World Applications: Case studies from molecular toxicity modeling to global ecosystem analysis.
Critical Conversations: Discussions on ethical, legal, and technical challenges in AI adoption.
Collaborative Insights: Engaging panels and interactive polling to shape the future of AI in safety science.
Poster Session: A platform to showcase cutting-edge research and exchange ideas with experts across disciplines.
Strategic Roadmap: A final session synthesizing key takeaways into actionable next steps for AI-driven innovation for human and environmental health protection.

Who Should Attend?

• Scientists & Researchers
• Industry Experts & Innovators
• Regulators & Policymakers
• AI & Data Science Professionals

Be part of the conversation shaping the responsible and effective use of AI in human and environmental health protection.

Full details and registration link available here: https://hesiglobal.org/hesiannualmeetings/

HESI is pleased to announce that several of its scientific programs will be featured at the 2025 Annual Meeting of the Genetic Toxicology Association (GTA). This year’s meeting will spotlight innovative approaches to genotoxicity and carcinogenicity testing, and HESI is proud to contribute through multiple committee-led presentations that reflect our mission to collaboratively advance science for a safer, more sustainable world.

HESI-Led Workshop, Wednesday May 7th, 4:00-6:00PM ET
“The Last Mile: Opportunities to Bridge Research and Increase Impact in Human and Environmental Health Sciences
Session Chairs: Raechel Puglisi (HESI) & Connie Chen (HESI)

• Raechel Puglisi (HESI): Defining the Last Mile: The Bridge Between Research and Impact (GTTC)
• Srijit Seal (Merck): HESI eSTAR OASIS: Leveraging ‘Omics Data for Next Gen Safety Assessment (eSTAR)
• Stefan Pfuhler (Procter & Gamble): HESI Botanical Safety Consortium: Towards a Global Genotoxicity Testing Strategy for Botanicals (BSC)
• Carole Yauk (University of Ottawa): From Discovery to Validation and Implementation: The Journey of the TGx-DDI Biomarker (eSTAR)

Additional HESI Presentation:
James Alper Alcaraz (University of Ottawa): Toward More Predictive and Human-Relevant Carcinogenicity Testing: Establishing Study Design and Approach for Detecting Cancer Driver Gene Mutations Using Duplex Sequencing (eSTAR)

This dynamic presence at GTA 2025 highlights HESI’s multi-sector commitment to translating cutting-edge science into practical tools that inform decision-making and regulatory guidance. We invite all attendees to join these sessions and engage with HESI staff and collaborators on the latest in genetic toxicology innovation.

HESI is pleased to announce that several of our collaborative scientific committees will be featured at the SETAC Europe 35th Annual Meeting, taking place 11–15 May 2025 in Vienna, Austria.

Presentations from the Next Generation Ecological Risk Assessment Committee, the UVCBs and Multi-Constituent Substances (MCS) Committee, and the Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee will highlight HESI’s ongoing contributions to advancing tools and methodologies for environmental and human health risk assessment.

Topics span critical areas such as ecological exposure modeling, characterization and assessment of complex substances, and the application of high-throughput technologies in toxicology—all aligned with HESI’s mission to deliver collaborative science for a safer, more sustainable world.

Full presentation details are available on the HESI event page:
https://hesiglobal.org/event/setac-europe-35th-annual-meeting/

If you are attending SETAC Europe, we invite you to connect with HESI members and learn more about our work.

The HESI Cardiac Safety Committee has published a new study in the Journal of Pharmacological and Toxicological Methods exploring the use of corrected JT-peak (JTpc) and Tpeak-to-Tend (TpTec) intervals as potential biomarkers for assessing drug-induced proarrhythmia risk in nonclinical species. This collaborative research, conducted by a multi-stakeholder consortium, provides critical insights into the translational value of these ECG sub-intervals in evaluating cardiac safety and correlates to the work done by FDA scientists on clinical ECGS (Vicente et al., 2018 doi10.1002/cpt.1303).

Understanding how these biomarkers perform in preclinical models is essential for improving the prediction of cardiac risks in humans and refining regulatory safety assessments. The findings highlight the complexities of translating nonclinical data into clinical outcomes and underscore the need for continued innovation in cardiac safety testing.

Read the full study here:
Assessment of corrected JT-peak (JTpc) and Tpeak-to-Tend (TpTec) as proarrhythmia biomarkers in non-human primates: Outcome from a HESI consortium. Boulay et al., 2024. Journal of Pharmacological and Toxicological Methods. https://doi.org/10.1016/j.vascn.2024.107543

As part of its Nitrosamine Research Program (NRP), HESI’s Genetic Toxicology Technical Committee (GTTC) has supported the publication of a new study evaluating the relative CYP enzyme activities in uninduced and induced hamster and rat liver S9 preparations. This research is critical for assessing the metabolic activation of potentially carcinogenic N-nitrosamine impurities, particularly in the Ames test, which relies on rodent liver S9 for metabolic activation.

Previous Ames test results have shown inconsistencies in detecting mutagenicity for some N-nitrosamines. To address this, both rat and hamster liver S9 preparations were analyzed for their ability to activate N-nitrosamines into their mutagenic forms. Findings confirm that both species exhibit relevant P450 enzyme activities for N-nitrosamine bioactivation. However, hamster liver S9 demonstrated higher overall P450 activity, supporting its recommendation for regulatory genotoxicity testing of N-nitrosamines in vitro.

Read the full publication to learn more about these findings and their implications for regulatory testing.

A comparative analysis of select P450 enzymes in uninduced and PB/BNF-induced hamster and rat liver S9. Evans et al., 2025. Mutation Research – Genetic Toxicology and Environmental Mutagenesis. https://doi.org/10.1016/j.mrgentox.2025.503855

For more information about the GTTC or NRP, please reach out to any of the managers: Connie Chen, Raechel Puglisi or Alexandra Taraboletti.

The HESI Immunotoxicology Technical Committee (ITC) and Developmental and Reproductive Toxicology (DART) Committee are excited to share our latest publication in the Journal of Reproductive Immunology!

Publication overview
This paper explores the impact and risk of immunomodulatory compounds on pregnancy, summarizing key insights from a joint HESI ITC/DART survey and workshop. The study examines immune mechanisms during pregnancy, the adequacy of current tools for assessing risk, and global regulatory considerations across different immunomodulatory therapies.

Why is this important?
For patients and clinicians, making informed medical decisions during pregnancy is one of the most critical moments in life. As immunomodulatory treatments become more common for conditions like autoimmune diseases and cancer, understanding their effects on pregnancy is important for ensuring both maternal and fetal health. This publication provides helpful insights to support decision-making by summarizing current scientific understanding and assessment approaches.

Read the full article here:
Assessing the impact and risk of immunomodulatory compounds on pregnancy. Kwak-Kim et al., 2025. Journal of Reproductive Immunology. https://doi.org/10.1016/j.jri.2025.104453

A newly published article in FACETS explores how the Health and Environmental Sciences Institute’s RISK21 framework can support more ethical, efficient, and inclusive human health risk assessments—specifically in Indigenous community contexts.

“Exploring the Use of the RISK21 Approach for Indigenous Community-Based Human Health Risk Assessments: Two Case Studies” (Chong et al., 2025) evaluates the utility of RISK21 in collaboration with the Chipewyan Prairie First Nation, Cold Lake First Nations, and the Apsáalooke/Crow Nation.

Indigenous communities often face disproportionate exposure to environmental contaminants, but conventional risk assessment methods do not always reflect the unique cultural, dietary, and socio-economic contexts that influence these risks. The authors piloted RISK21 as a tiered, exposure-driven tool that allows for flexible decision-making using both limited and detailed data. Notably, the tool was able to replicate key findings from conventional assessments, while using less data and providing an intuitive visual risk matrix.

The paper emphasizes both the promise and the limitations of current tools when applied in Indigenous contexts. Community members and researchers called for improvements to risk communication outputs and better integration of holistic and culturally relevant information.

By piloting RISK21 in these real-world cases, this study marks a crucial step toward modernizing health risk assessments in ways that are more responsive to community-specific needs. It also reinforces HESI’s mission to advance science that informs decisions and protects health across diverse populations.

Read the full open access article: https://www.facetsjournal.com/doi/pdf/10.1139/facets-2024-0085

On March 5th, HESI hosted its inaugural Networking Event in Washington, DC, bringing together over 30 scientists and professionals from across the public, private, and non-profit sectors. This event marked the first of its kind for HESI—designed to foster meaningful connections across disciplines and sectors within the health and environmental sciences community.

Attendees had the opportunity to engage with professionals representing a wide range of expertise, including toxicology, epidemiology, pharmacology, chemistry, modeling, science communication, AI/ML, regulatory sciences, and more. The evening served as a dynamic space for collaboration, mentorship, and career exploration—where individuals came together to expand their networks, share insights, and explore employment opportunities in both directions.

In the words of HESI’s Executive Director, Syril Pettit, “Smart, experienced, committed health and environmental professionals seeking to do good, make connections, and support (and hire) each other in challenging times. This was our first such event but won’t be our last!”

Thank you to all who attended and helped make the evening a success. We look forward to hosting similar events in the future to continue building bridges across the scientific community.

HESI is proud to announce the launch of the Nancy Doerrer Elevate Award, a new annual recognition celebrating individuals who exemplify collaborative and catalytic leadership within the HESI community.

Named in honor of Nancy Doerrer, HESI’s former Associate Director and a long-standing champion of HESI’s mission, this award acknowledges those who go above and beyond in engaging, strengthening, and advancing HESI’s programs and initiatives. Recipients of this distinguished award are individuals whose dedication and uplifting presence significantly enhance the HESI community.

We invite you to learn more about this exciting new opportunity and how you can nominate a deserving colleague. Visit https://hesiglobal.org/nancy-doerrer-elevate-award/ for details.

For questions, contact HESI at Elevate@hesiglobal.org

Let’s celebrate those who elevate HESI’s impact!

The HESI THRIVE 2025 Seed Grant Program is accepting Letters of Intent until April 7, 2025. This grant of up to $50,000 USD supports innovative research aimed at predicting, preventing, and reducing adverse effects from cancer therapy. To learn more about this unique funding opportunity, visit the webpage at https://hesithrive.org/.

Are you a postdoctoral or early career researcher working in cardiovascular safety science or a related field? The HESI Cardiac Safety Committee invites you to apply for the Early Career Seminar Award Series!

Award Details:

• $500 USD award
• Opportunity to present your research in a public webinar with leading experts from academia, regulatory agencies, and the pharmaceutical industry
• Network & gain insights from top scientists in toxicology and safety pharmacology

Eligibility:

• PhD or equivalent in biology or related fields (cell biology, biochemistry, pathology, biomechanical engineering, etc.)
• Currently in a postdoc position or early career stage (~1-5 years post-academic training)
• Open to both domestic & international applicants
• Must not have previously received this award

Deadline to Apply: April 25, 2025

For details on how to apply visit: https://hesiglobal.org/cardiac-safety/#earlycareeraward

Don’t miss this opportunity to showcase your work and connect with the HESI Cardiac Safety Committee! Know someone who should apply? Send them the weblink above!

The Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee (HESI GTTC) Education and Science Outreach Committee is pleased to announce that the 2025 award cycle is now open! These awards will provide opportunities for trainees to attend scientific conferences, workshops, or courses, etc., to build core competencies and transferable skills, and/or share their research. Awardees will be invited to GTTC’s 2026 Annual Meeting to learn about the emerging projects and science at HESI and to network with experts in the genetic toxicology field.

Two award categories:

• Professional Development Travel Award – Provides $1,500 USD for travel to attend scientific conferences or workshops.
• Professional Development Training Award (new!) – Provides $4,000 USD for travel specific to training courses, cross-lab trainings, etc., to build core competencies and transferrable skills.

Learn more and download the application here.

The Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee is excited to announce an expansion of its focus to include gene therapies as part of its ongoing commitment to advancing safety science in emerging advanced therapies. This addition reflects the growing importance of understanding and addressing safety concerns specific to these cutting-edge gene delivery systems, which are being increasingly utilized in clinical applications. By leveraging our existing expertise and global network, we aim to foster the development of best practices, innovative tools, and collaborative projects to support the safe translation of gene therapies to the clinic. Two new project proposals are on track to launch as new working groups in 2025: “Methods for Integration Site Analysis and Data Interpretation” and “Assessing Risk of Germline Transmission in AAV Gene Therapy Products” (the latter, in collaboration with HESI DART committee).

The committee is welcoming new partners with expertise in gene therapies development and their nonclinical safety assessment, with interest in advancing the field of safety science. Through our collaborative, pre-competitive forum, we aim to build a robust network of contributors. Reach out to committee managers Lucilia Mouriès and Connie Chen to express your interest and learn more.

HESI recognizes that the most pressing issues in environmental and public health cannot be solved in isolation. This is why we believe in fostering collaboration across disciplines and sectors, which allows our community to achieve a sum greater than our individual parts. HESI is built on this collaboration, which includes our colleagues in U.S. government agencies. We strongly value their participation and understand their important contributions to science.

HESI recognizes there is much uncertainty impacting many of the US federal agencies at this time. With this in mind, HESI recently convened a networking event to bring together members of our community. More than 50 people with varied backgrounds and expertise attended this event to expand their professional networks, exchange ideas, and spark new collaborations.

HESI is a connector, and we hope to maintain this for years to come, and through our connections and scientific work, continue to advance innovation in public and environmental health.

Jennifer Pierson, MPH
Associate Director for Program Development & Resourcing