HESI Insights May 2025

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’s Cell and Gene Therapies Safety Committee (CGT-TRACS) has officially launched DPICT (Data Portal for Imaging Cell Therapies), a new, publicly accessible online database developed by the committee’s Point-of-Administration/Biodistribution Working Group.

What is DPICT?
DPICT is an open-access resource designed to support the cell therapy community by providing curated data from peer-reviewed studies that utilize in vivo cell-tracking methods to evaluate the biodistribution and fate of therapeutic cells post-administration in clinical settings.

Key Features Include:

• A searchable database of clinical imaging studies
• An open submission form for new data contributions, reviewed by the DPICT Steering Team
• A Resources tab offering educational tools and reference materials
• An About page that explains the initiative’s goals, scientific leadership, and future vision

DPICT is intended to serve scientists, developers, regulators, educators, and students alike. It supports HESI Global’s mission to advance safety science through transparency, collaboration, and accessibility.

Explore the database and contribute to its growth here: DPICT – Data Portal for Imaging Cell Therapies

The HESI Transforming the Evaluation of Agrochemicals (TEA) Committee is happy to announce that Dr. Huan Yang is the inaugural winner of the TEA Global Challenge. This international competition was launched to promote innovative thinking around the future of agrochemical safety assessment. The challenge aimed to showcase the feasibility of new approach methodologies (NAMs), encourage cross-sector collaboration, and fostered global knowledge sharing.

Dr. Yang, an independent consultant with a PhD in Applied Mathematics, impressed the TEA Committee with his case study applying scalable digital tools to support next-generation risk assessment (NGRA). His work integrates physiologically based kinetic models and quantitative effect modeling within the adverse outcome pathway framework, leveraging both in vitro and in vivo data. Dr. Yang’s background includes collaborative projects funded by EU Horizon 2020, NC3Rs, Dutch NWO, and BMBF-ZonMW.

As the inaugural awardee, Dr. Yang received $2,000 in travel support, which he used to attend SETAC Europe, where he further engaged with the international environmental science and chemical safety community.

HESI Global proudly celebrates Dr. Lyn Jones, Public Sector Chair of the Targeted Protein Degrader Safety (TPDS) Committee, on his recent election as a Fellow of the Learned Society of Wales. This prestigious honor recognizes individuals who have demonstrated significant expertise, innovation, and leadership in research and public service, and reflects Dr. Jones’ outstanding contributions to science and society—both in his professional field and in his homeland of Wales.

The Learned Society of Wales is the national academy for the sciences, arts, and humanities in Wales, drawing its Fellows from across academia, public and health services, and civic life. Election to the Society is a highly selective process, grounded in demonstrated excellence and the capacity to influence society through knowledge. For Dr. Jones, this fellowship carries special meaning as a native of Wales and as a representative of public sector science leadership on the global stage.

Dr. Jones’ work on the TPDS Committee aligns closely with HESI’s mission to collaboratively identify and help resolve global health and environmental challenges. Under his leadership, the committee has spearheaded efforts to evaluate the safety of targeted protein degradation therapies—an emerging and highly promising class of therapeutics—through the development of innovative scientific strategies, cross-sector dialogue, and translational safety assessment frameworks.

His recognition by the Society underscores the importance of applied scientific excellence and collaborative leadership—hallmarks of the HESI community. It also reflects the broader impact of our programs in shaping not only regulatory science and translational research, but also the real-world advancement of public health across geographies.

Please join us in congratulating Dr. Jones on this exceptional achievement!

HESI Global is honored to recognize the outstanding contributions of Dr. Anne Carpenter from the Broad Institute of MIT and Harvard for her transformative impact in the fields of computational biology and image-based profiling. Her visionary leadership and pioneering work have significantly advanced the mission of data-driven discovery and innovation in biomedical research.

Dr. Carpenter’s research career has centered on the development of cutting-edge methodologies that enable high-throughput, quantitative analysis of cellular images. She is the pioneering scientist behind the Cell Painting assay, a powerful method for capturing rich cellular phenotypes using multiplexed microscopy, and the co-creator of CellProfiler, an open-source software platform that has revolutionized how researchers extract biological insights from microscopy data. These tools have enabled scientists worldwide to uncover insights into drug mechanisms, gene functions, and disease biology.

Her contributions have been instrumental in promoting unbiased, data-rich approaches to phenotypic screening. Through the Broad’s Imaging Platform, which she helped build, Dr. Carpenter has championed the use of image-based profiling for functional characterization of genes, drugs, and disease states. Her work has illuminated the potential of machine learning and artificial intelligence in translating complex image data into actionable biological knowledge.

Dr. Carpenter’s career has been marked by numerous honors and achievements, including being named to the Stat News STATUS 2025 List, election as a Fellow of the American Institute for Medical and Biological Engineering, and recognition by prominent scientific outlets for her work in computational biology. Her leadership continues to shape the future of biomedical imaging and data science.

Dr. Carpenter also serves as a leading force behind HESI’s Omics for Assessing Signatures for Integrated Safety (OASIS) Consortium. This project aims to gain confidence in the combination of Cell Painting, transcriptomics and proteomics for safety assessment using hepatotoxicity as use-case. She and her collaborator Dr. Shantanu Singh successfully applied and were awarded a grant to conduct the massive laboratory work for the project. Additionally, industry funds for the consortium support a post-doctoral fellow in their joint lab, whom Dr. Carpenter mentors.

HESI extends its deepest appreciation to Dr. Anne Carpenter for her exceptional dedication, scientific ingenuity, and lasting contributions to the global research community.

Take part in the NC3Rs stakeholder engagement survey on new approach methodologies! If you are involved in the development and application of replacement technologies for toxicity testing or the submission and assessment of data for regulatory decision making, this is your opportunity to tell us your priority areas and unmet needs that if addressed would facilitate the use of new approach methodologies in safety assessment.

This work is supported by our new expert cross-sector advisory group – NC3Rs Regulatory Science Forum

Take the survey HERE.

The CGT-TRACS Committee has published a position paper in Cytotherapy that provides consensus expert recommendations on evaluating teratoma formation risk in human pluripotent stem cell (hPSC)-derived cell therapy products.

This paper follows the first and widely cited output from this HESI committee (Sato et al. 2019), integrating learnings from its work since then and current state of the science on the topic.

Pluripotent stem cells offer immense promise to treat conditions that lack effective therapies. However, their ability to form teratomas, a type of tumor composed of multiple tissue types, poses a significant safety concern when residual undifferentiated cells remain in the final cell therapy product. Current regulatory frameworks require rigorous safety assessments, typically including in vivo tumorigenicity assays. However, the translational relevance of traditional in vivo assays for cell-based therapies is debated, as these models presuppose that human cells will exhibit comparable behavior in animal hosts and in the human physiological environment.

This publication:

• Reviews the limitations of traditional in vivo teratoma assays.
• Compares emerging in vitro methods such as droplet digital PCR (dPCR) and highly efficient culture (HEC) assays.
• Presents findings from multi-site validation studies showing these in vitro approaches offer significantly greater sensitivity and reproducibility than current in vivo methods.
• Provides practical guidance for integrating these assays into product quality control frameworks.
• This consensus paper represents a significant advancement toward the global harmonization of tumorigenicity assessment in regenerative medicine. It supports HESI Global’s mission to resolve global health challenges through collaborative science, and it equips developers and regulators with robust tools to enhance the safety of next-generation cell therapies.

Read the full paper here:

Watanabe et al. 2025. Evaluating teratoma formation risk of pluripotent stem cell-derived cell therapy products: a consensus recommendation from the Health and Environmental Sciences Institute’s International Cell Therapy Committee. Cytotherapy, DOI: 10.1016/j.jcyt.2025.04.062

The GTTC Committee has published a study in Regulatory Toxicology and Pharmacology titled, “HESI GTTC Ring Trial: Concordance between Ames and Rodent Carcinogenicity Outcomes for N-Nitrosamines with Rat and Hamster Metabolic Conditions.” This study addresses a critical public health and regulatory issue: how to effectively detect and assess the mutagenic and carcinogenic risks posed by nitrosamine impurities in medications.

Why this matters:
N-nitrosamines (NAs) are genotoxic impurities that can be introduced during pharmaceutical manufacturing. Several NAs are known potent rodent carcinogens, and their presence in drugs has sparked global concern. Accurate, reproducible testing of their mutagenic potential is essential to ensure drug safety, yet traditional bacterial mutation assays (like the Ames test) often yield inconsistent results under standard conditions.

The problem:
Regulatory bodies have expressed concern over the limited sensitivity of the standard Ames test for detecting nitrosamine-related mutagenicity, leading to calls for enhanced testing protocols. Yet, there has been no consensus on how to modify the assay for optimal performance.

HESI’s solution:
In a multi-laboratory ring trial, the GTTC tested 32 NAs and NA-like compounds using multiple bacterial strains and varying metabolic activation systems derived from rats and hamsters. The goal: determine which assay conditions best predict known rodent carcinogenic outcomes.

The study found that using 30% hamster liver S9 metabolic activation provided the highest sensitivity (90–93%) in identifying carcinogenic NAs. Furthermore, combining 30% hamster and rat S9 fractions maintained high reproducibility between labs (91%)—supporting the robustness and reliability of the approach.

Why this is beneficial:
This research validates enhanced Ames testing protocols now recommended by global regulators and provides a scientifically grounded, harmonized framework for industry and regulators to assess the risk of nitrosamine impurities. By improving the predictive power of in vitro testing, this work helps reduce reliance on animal studies and enhances public confidence in pharmaceutical safety assessments.

Aligned with HESI’s mission to resolve global health challenges through collaborative science, this study exemplifies how cross-sector partnerships can produce actionable science that safeguards public health.

Read the full publication here:

HESI GTTC Ring Trial: Concordance between Ames and Rodent Carcinogenicity Outcomes for N-Nitrosamines (NAs) with Rat and Hamster Metabolic Conditions. Bercu et al., 2025. Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2025.105835

The Botanical Safety Consortium has a new publication that demonstrates how computational modeling can streamline safety evaluations of botanical products. Using the Extended Clearance Classification System (ECCS), the researchers predicted how 82 phytochemicals from 13 botanicals are processed in the human body—whether through liver metabolism, hepatic uptake, or renal clearance. Over half of the constituents were classified as being predominantly metabolized by liver enzymes such as CYP3A4, CYP2D6, and CYP1A2, indicating a higher potential for drug-botanical interactions. Conversely, around 20% of the compounds were predicted to be cleared unchanged via the kidneys. This work provides a practical, scalable framework for predicting the absorption, distribution, metabolism, and excretion (ADME) of complex botanical mixtures, supporting more efficient risk assessments without requiring extensive animal studies. The approach aligns with emerging new approach methodologies (NAMs) and offers toxicologists a valuable tool for understanding botanical safety profiles in a regulatory context.

Integration of computational models to predict botanical phytochemical constituent clearance routes by the extended clearance classification system (ECCS). Liu et al., 2025. Toxicology and Applied Pharmacology. https://doi.org/10.1016/j.taap.2025.117385

The Immuno-Safety Technical Committee (ITC) hosted its virtual Spring-Summer Science Summit on April 22–23, 2025, bringing together experts across sectors for two half-days of focused discussion and scientific momentum. This year’s theme, “Fueling Progress: Advancing New Projects and Maintaining Momentum,” reflected the committee’s commitment to timely, high-impact work.

Key sessions spotlighted emerging and ongoing initiatives, including:

• CIVM (Clinical Immune-Related Adverse Event Mapping)
• Best Practices for Cytokine Release Assays (CRA)
• Translational Relevance of Non-Human Primates (NHPs)
• Comparative Immunobiology: Preclinical species selection for immune safety assessment
• A Retrospective Analysis on the translatability of nonclinical immune findings to clinical outcomes
• AI/ML-Powered Weight of Evidence Frameworks for carcinogenicity
• 3Rs-driven Approaches for evaluating biologics without reliance on traditional models

In between rich scientific discussions, attendees enjoyed a creative break with the unveiling of the new ITC T-shirt—a wearable conversation starter designed to spark curiosity and elevate visibility of the committee’s mission at professional meetings.

With strong community engagement and a growing portfolio, the ITC looks ahead to a year of productivity, innovation, and intentional outreach to advance the science of immuno-safety.

On May 13, 2025, the HESI Immuno-Safety Technical Committee (ITC) Comparative Immunobio workstream hosted a roundtable titled “This Little Piggy Went to Tox: Mini Pigs in Biologics Safety” to explore the role of Göttingen minipigs in biologics safety evaluation. In the context of the FDA’s recent roadmap to phase out animal testing for monoclonal antibodies (mAbs), this timely discussion evaluated whether minipigs can serve as scientifically credible and ethically aligned alternatives during the transition toward human-based new approach methodologies (NAMs).

Dr. Lars Siim Madsen, Chief Scientific Officer of Ellegaard Göttingen Minipigs, presented an overview of the minipig’s immunological relevance and highlighted recent developments in a humanized minipig model expressing human IgG1 and IgG4. His presentation emphasized the model’s pharmacological relevance, translational value, and practical applications in biologics development.

The audience raised questions that covered:

• The model’s global availability
• Limitations of the model due to the minipig’s lack of binding to Fc gamma receptor IIIA (FcγR3A)—a critical receptor expressed on human natural killer (NK) cells that mediates ADCC responses
• Pathology interpretability and innate immune function
• Use of minipigs for cytokine storm and single-dose mAb studies

This session sets the stage for continued regulatory engagement and new collaborative validation projects. It also complements the ITC’s upcoming manuscript in mAbs, titled: “Impact of Antibody Fc Engineering on Translational Pharmacology and Safety: Insights from Industry Case Studies,” where authors offer a practical roadmap for selecting nonclinical models and interpreting Fc-modified antibody behavior in safety studies in a very comprehensive review.

HESI Global was proud to participate in the SETAC Europe 35th Annual Meeting in Seville, Spain, last week. Several of HESI’s multi-sector scientific committees presented cutting-edge research supporting the institute’s mission to collaboratively develop science for a safer, more sustainable world.

The Next Generation Ecological Risk Assessment Committee was very busy! A poster was presented exploring how avian life history traits impact exposure assessments of environmental chemicals—highlighting innovative methods to improve ecological safety evaluations. The bird in vitro method development project, funded by HESI, was highlighted in a presentation by Matthew Schultz (U of Saskatchewan). Additionally, Julie Krzykwa gave a presentation and live demonstration of the EnviroTox Database and tools in a session on “In Silico NAMs for Enhancing Understanding of Chemical Safety”. Lastly, several posters highlighting the recently published OECD Bioaccumulation IATA were presented with HESI co-authors, and a small brainstorming meeting was held the day prior to the conference to discuss next steps in the bioaccumulation assessment field.

The UVCBs and Multi-Constituent Substances (MCS) Committee delivered both a poster and a platform presentation on advancing approaches for characterizing and assessing complex substances (UVCBs), sharing data from their pilot database and emphasizing the importance of fit-for-purpose testing strategies.

The Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee showcased a platform presentation from Jessica Ewald (Broad Institute) on using Cell Painting to assess the cytotoxicity and mode-of-action of over 1,000 compounds—demonstrating the utility of new approach methodologies (NAMs) in modern toxicology.

Michelle Embry presented a summary of the bioaccumulation recommendations in a session on “European Commission Roadmap Towards Phasing Out Animal Testing for Chemical Safety Assessments.” The work was part of a European Partnership for Animal Alternatives to Animal Testing (EPAA) initiative that was recently completed.

SETAC Europe continues to be a key forum for knowledge exchange and collaboration across sectors, and HESI Global was excited to engage with partners new and old in support of its global health and environmental goals.

Check out our photos from the event!

At the 2025 Genetic Toxicology Association (GTA) Annual Meeting, HESI Global co-hosted a workshop titled “The Last Mile: Opportunities to Bridge Research and Increase Impact in Human and Environmental Health Science.” Co-chaired by Raechel Puglisi, MPH, and Connie Chen, PhD, MPH, the session focused on how to close the gap between scientific discovery and real-world application, particularly in the field of genetic and genomic toxicology.

The workshop featured four case studies from three HESI Global programs – GTTC, eSTAR, and the Botanical Safety Consortium – each illustrating different pathways to translate foundational research into regulatory and public health impact. The session concluded with a lively panel discussion on how to design science with implementation in mind, engage stakeholders early, and foster meaningful uptake of tools and data.

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 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.

Are you a graduate student or postdoc working in developmental or reproductive toxicology—or a related field? This is your opportunity to take your research and training to the next level!

The HESI Developmental and Reproductive Toxicology (DART) Committee is now accepting applications for the 2025 Professional Development Awards.

Why Apply?
Two selected candidates will each receive a $2,000 USD award to support attendance at a scientific conference, training course, or another professional development activity. Whether it’s presenting your research, gaining new skills, or visiting a lab to expand your toolkit, this is a fantastic way to advance your career and contribute to the science. This award is more than funding—it’s visibility, network-building, and a steppingstone to leadership in the DART field.

Who Should Apply?
Eligible applicants must be:

• Currently enrolled in a graduate program (MS or PhD), or
• In a postdoctoral position (no more than 5 years out), and
• Working in developmental or reproductive toxicology, or a closely related scientific field.

The HESI DART Committee is a passionate proponent of collaborative science and firmly believes that advancing science requires the participation and perspectives of a diverse community. We know that meaningful progress happens when there is richness of thought and representation across disciplines and experiences—and we welcome applicants who are ready to be part of that vision.

Application Deadline: May 31st, 2025

Don’t miss your chance to be one of our 2025 awardees! This is your moment. Let us help you grow.

Apply 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.

Dear HESI Global Community,

I hope everyone is doing as well as possible. Thank you for all you do, especially thus far in 2025, for our HESI Global Community and our collective friends, colleagues, and networks!

In just 2 weeks – I hope to see you in D.C. June 4-5 to help HESI Global build a roadmap toward responsible and effective use of AI in human and environmental health protection.

We will meet at a prestigious venue – the National Academy of Sciences Kavli Auditorium – at an important time in history to foster collaborative dialogue by scientists and researchers, industry experts and innovators, regulators and policymakers, and AI and data science professionals.

We have an impressive agenda and lineup of speakers, including renowned experts in AI, health, and environmental sciences:

2 Prominent Keynote Speakers:

• Dr. Robert Califf (Day 1) will prompt dialogue on whether or not regulatory science is ready for AI.
• Dr. Shaolei Ren (Day 2) will prompt dialogue on potential hidden and public health impacts of AI.

4 Sessions Considering Molecular Level to Population:

• Molecular Initiating Events and Cellular Responses: Tackling challenges to understanding complex toxicity and exposure pathways with novel computational and AI methods.
• Understanding Organism and Population Responses to Stressors – Potential for Expanding Study Design, Diversity of Exposure Scenarios, and Study Feasibility with Virtual Elements.
• Ecosystem and One-Health (Human, Ecological, & Environmental) Protection and Prediction – Can AI Help Us with Global Scale Health Protection?
• Exploring the Last Mile of Implementation – Legal, Ethical, Environmental considerations for real-world AI applications in health and environmental sciences.

1 Dynamic Poster Session:

• Opportunity for you or your team members to present during a poster session (deadline May 23rd).

If you overlooked this meeting, please consider registering to attend and provide a poster to be part of this transformative journey!

Warm regards,
Gary

Gary Minsavage, PhD, DABT, MBA
HESI Board of Trustee Member and President of Assembly