HESI Global Insights December 2025

The Health and Environmental Sciences Institute (HESI Global) is pleased to announce the 2025 THRIVE grants to support research aimed at minimizing side effects of cancer treatment and improving quality of life. This year’s recipients—Drs. Alexandre Chan, Lisa Feldman, and Yuming Jiang—are leading innovative research to predict, reduce, or prevent adverse treatment impacts so patients and survivors can thrive.

“Nearly forty percent of the population will face a cancer diagnosis in their lifetime – we are all touched by cancer in some way. And with life-saving therapies and improved drug efficacy, cancer survivorship continues to grow,” said Syril Pettit, DrPH, MEM, Executive Director of HESI. “It’s crucial that we address treatment-related toxicity so survivors can experience not only more years, but better years. These projects help make that possible.”

The 2025 THRIVE awardees were selected from a highly-competitive international pool. Each recipient will receive $50,000 to advance their novel research.

Alexandre Chan, PharmD, MPH, University of California, Irvine: Improving cognition deficits caused by radiation to the head – Dr. Chan’s team will study whether a well-tolerated medication, riluzole, can boost a natural brain protein that supports thinking, memory and learning, helping survivors regain sharper cognitive function and independence.

Lisa Feldman, MD, PhD, City of Hope: Creating less invasive and more personalized approaches to treatment for glioblastoma – Dr. Feldman’s team will develop a “liquid biopsy” that uses a simple sample of blood or spinal fluid to look for tiny tumor-derived particles. This has the potential to provide a safer and less invasive alternative for monitoring tumor progression and treatment response and could guide more personalized immunotherapy treatments that reduce toxicity and optimize efficacy.

Yuming Jiang, MD, PhD, Wake Forest University School of Medicine: Reducing treatment-related toxicities for esophageal cancer patients – Dr. Jiang’s team will develop an AI-powered approach to better predict which esophageal cancer patients are most likely to respond to neoadjuvant chemoradiotherapy (nCRT), aiming to spare nonresponders from severe toxicity when there is a lack of clear benefit.

Since the THRIVE program began in 2017, HESI has awarded nearly $1.4 million in grants, providing researchers with seed funding for innovative work that bridges laboratory science and applied medicine. This work has been translated into findings that can improve patient outcomes, has spurred expanded research and collaboration, and raised awareness of the patient experience of cancer treatment. THRIVE supports translational researchers in generating proof-of-concept data needed for long-term funding and strengthens quality of life as a core research priority.
More information about past awardees and upcoming grant cycles is available at www.hesithrive.org.

HESI Global is a globally operating science 501c3 nonprofit whose mission is to collaboratively identify and help resolve global health and environmental challenges through the engagement of scientists from academia, government, industry, the clinic, NGOs and other strategic partners. The mission is achieved through creating a collaborative environment where scientists can design and implement meaningful research to enhance human and environmental health. www.hesiglobal.org

As we celebrate this year’s 2025 THRIVE Grant Winners, we’re also pleased to recognize a major recent honor earned by a longtime HESI Global collaborator. Dr. Steve Lipshultz—a founding member of the HESI THRIVE Advisory Board and a valued contributor to the HESI Cardiac Safety Committee—was named an American Heart Association (AHA) Distinguished Scientist and received the award in November at the AHA’s annual Scientific Sessions.

The AHA Distinguished Scientist designation recognizes sustained, significant scientific contributions that advance cardiovascular and stroke research, with honorees recognized annually at AHA Scientific Sessions.

Congratulations from all of us at HESI Global, Dr. Lipshultz, on this well-deserved recognition!

This month we are thrilled to recognize Dr. Eliana Munarriz (Universidad de Buenos Aires) for her continued service as a Steering Team Member of the HESI Global Transforming the Evaluation of Agrochemicals (TEA) Committee. Her leadership and scientific insight play a pivotal role in strengthening TEA’s global engagement and impact.

A defining example of her contributions occurred on August 26, 2025, when the TEA Committee – supported by the HESI Global Risk Assessment Training Center (GRATC) and in collaboration with SETAC Latin America – hosted a regional symposium on the safety evaluation of agrochemicals in South America. The event convened more than 20 regulatory scientists from 9 Latin American countries, along with representatives from academia and industry, for a focused dialogue on regional needs, scientific priorities, and opportunities for collaboration.

This symposium offered an essential platform for regulators and other stakeholders to exchange perspectives and identify shared challenges in evaluating plant protection products. The insights gathered are already informing TEA’s strategic direction and helping ensure that the committee’s conceptual model and emerging work products remain relevant across diverse regulatory contexts.
The success of this meeting was due in large part to Dr. Munarriz’s leadership and deep relationships within the region. Her longstanding efforts to connect HESI Global with Latin American regulatory communities were instrumental in securing broad participation and fostering a constructive, trusted environment for discussion.

Beyond this symposium, Dr. Munarriz has played a major role in advancing scientific capacity throughout Latin America through her work with RISK21, GRATC, and the PAHO Virtual Campus. Her ability to translate complex concepts into accessible, actionable tools has equipped hundreds of practitioners with modern approaches to risk assessment. As a TEA Steering Team member, she brings this same commitment and collaborative spirit to shaping TEA’s priorities and outputs.

Thank you, Eliana, for your exemplary leadership within TEA and for your dedication to advancing scientific capacity and regulatory collaboration worldwide!

Advancing botanical safety relies on rigorous data and emerging scientists who are willing to dive deep into it.

The Botanical Safety Consortium is pleased to recognize the contributions of Ms. Hilva Gjoni, PhD student in Food Chemistry at the Università degli Studi di Parma, working under Professor Chiara Dall’Asta. As part of her PhD training, Hilva joined the Consortium this fall to gain experience beyond her home laboratory.

During her time with us, Hilva:
• 𝐑𝐞𝐯𝐢𝐞𝐰𝐞𝐝 𝐚𝐧𝐝 𝐬𝐮𝐦𝐦𝐚𝐫𝐢𝐳𝐞𝐝 𝐭𝐨𝐱𝐢𝐜𝐢𝐭𝐲 𝐥𝐢𝐭𝐞𝐫𝐚𝐭𝐮𝐫𝐞 𝐟𝐨𝐫 𝐬𝐞𝐯𝐞𝐫𝐚𝐥 𝐛𝐨𝐭𝐚𝐧𝐢𝐜𝐚𝐥𝐬 including bergamot, cinnamon, and Asian ginseng, with a focus on skin sensitization, irritation, and phototoxicity to support the Dermal Working Group’s strategy paper (to be submitted early next year).

• 𝐀𝐧𝐚𝐥𝐲𝐳𝐞𝐝 𝐡𝐞𝐩𝐚𝐭𝐨𝐭𝐨𝐱𝐢𝐜𝐢𝐭𝐲 𝐝𝐚𝐭𝐚𝐬𝐞𝐭𝐬 generated by the Hepatotoxicity Working Group, exploring concentration–response relationships across multiple assays, including LDH release and MT-Glo.

• 𝐈𝐝𝐞𝐧𝐭𝐢𝐟𝐢𝐞𝐝 𝐭𝐫𝐞𝐧𝐝𝐬 𝐚𝐧𝐝 𝐬𝐲𝐧𝐭𝐡𝐞𝐬𝐢𝐳𝐞𝐝 𝐟𝐢𝐧𝐝𝐢𝐧𝐠𝐬 that will help jump-start the Hepatotoxicity Working Group’s upcoming data write-up.

Through this work, Hilva expanded both her scientific knowledge base and her professional network, while helping the Consortium move forward on key projects.

We sincerely thank Hilva for her hard work, curiosity, and commitment to botanical safety.

With the support of the HESI Genetic Toxicology Technical Committee (GTTC) Professional Development Training Award and HESI Emerging Systems Toxicology for Risk Assessment Committee (eSTAR) through the Mitacs Elevate postdoctoral fellowship, I recently visited the Wellcome Genome Campus in Hinxton, UK, the University of Cambridge, and GSK’s laboratories in Stevenage. My primary objective was to step outside the immediate scope of my daily postdoc work and contextualize our ecNGS research within the broader landscape of high-throughput genomics. I wanted to deepen my understanding of recent developments in genomics and bioinformatics and to explore how advanced sequencing and imaging technologies can be translated into scalable tools for regulatory toxicology. I was able to critically refine my current thinking on error-corrected NGS (ecNGS) and clonal expansion in the context of some of the world’s leading genomics workflows, particularly how to move from specialised academic protocols toward scalable, standardised workflows suitable for regulatory acceptance. I was particularly impressed by the scale of resources and infrastructure, the industrial-grade laboratory automation and data handling designed for high-throughput operation, the depth of technical expertise, and the strong culture of collaboration across both academic institutions and industry.

A major highlight was the intensive Genome bioinformatics: from short- to long-read sequencing workshop at EMBL-EBI, which substantially expanded my computational toolkit. The course focused on rigorous development, automation, and scaling of genomics pipelines, including emerging approaches that integrate short- and long-read sequencing data. This training will directly strengthen how I design and analyse ecNGS and related studies. Complementary to this, working with Dr. Jessica Ewald’s group at EMBL-EBI provided foundational training in Cell Painting, from assay design to high-content feature extraction. The potential to combine these rich morphological profiles with our genomic data represents a massive opportunity to better understand mechanisms of action in toxicology and develop a mechanism-based risk assessment. Discussions with Dr. Raheleh Rahbari’s group at the Wellcome Sanger Institute and Dr. Alex Cagan at the University of Cambridge on cancer genomics and NanoSeq-based ultra-low-error sequencing clarified use-cases for ecNGS methods, particularly for detecting early clonal dynamics, and how ecNGS approaches can be used to map somatic evolution in normal tissues and experimental models. The visit to GSK, hosted by Dr. Anthony Lynch and Dr. Sujath Abbas, added an important industry perspective, demonstrating how large-scale genomics, screening, and data infrastructure can be deployed in a highly applied industry environment and highlighting concrete routes for translating ecNGS and related methods into industrial and regulatory contexts.

This trip has had a tangible impact on how I envision my future research career. I return with a clearer idea for a research programme that integrates genomics, image-based profiling, and advanced bioinformatics into a coherent framework that can ultimately support regulatory decision-making.

I am deeply grateful to HESI, the GTTC, Mitacs, and my hosts at GSK, the Wellcome Sanger Institute, EMBL-EBI, and the University of Cambridge for this opportunity. I look forward to continuing these discussions, pursuing future collaborations and translating these lessons into shared resources and collaborative studies for the HESI community, to help to advance the next generation of carcinogenicity testing and risk assessment.

Article by James Alper Alcaraz, University of Ottawa

Regretfully and with much sorrow, we share that James E. “Jim” Gibson, PhD passed away on November 22.

Jim was among the original group of individuals who played a key role in the founding of HESI as a distinct component of ILSI, and he provided steadfast leadership through many years of service on the HESI Board and Executive Committee. He began his career as a faculty member at Michigan State University before becoming the inaugural Vice President for Research at the Chemical Industry Institute of Toxicology (CIIT), where he helped build the scientific staff and launch CIIT’s research and postdoctoral training programs. He later served as Vice President for Global Regulatory Affairs at Dow AgroSciences.

We have lost a valued friend, and toxicology has lost a powerful voice for reason, scholarship, and excellence.

Jim’s obituary is available here.

We’re pleased to share that April Kleuver, PhD, DABT will join HESI Global in January as a Senior Program Advisor, supporting our chemical safety and risk assessment programs. April brings deep federal leadership experience, including serving as a DOE Office Director and regulatory lead for PFAS, where she founded the first interagency PFAS Working Group of Executive Branch chief scientists. Her background also includes roles as Deputy Director of Chemical Safety at the White House Council on Environmental Quality, Senior Toxicologist in the Executive Office of the President (2018–2023), and Senior Toxicologist at FDA. April is also a long-time HESI DART member, and we’re excited to welcome her expertise and collaborative spirit to the team.

We’re also excited to welcome Dominick J. Laddy, PhD, PMP, joining in January as a Senior Scientific Program Manager, supporting a range of patient and drug safety programs. Dominick brings extensive experience leading cross-functional clinical and nonclinical development efforts, including work at Barinthus Biotherapeutics on vaccine development against MERS-CoV, and at the International AIDS Vaccine Initiative (IAVI) managing nonclinical and clinical programs for mRNA vaccines, including NIH grant-supported work. He also served as Director of Preclinical Models and Biomarker Discovery at AERAS, and holds a PhD in Pharmacological Sciences from the University of Pennsylvania.

Please join us in welcoming April and Dominick to HESI Global!

The HESI Developmental and Reproductive Toxicology (DART) Committee is pleased to share the publication of its second manuscript in a series on new approach methodologies for developmental and reproductive toxicology. This manuscript highlights a modern, hypothesis-driven approach to developmental toxicity testing that moves beyond traditional animal studies by focusing on the biological mechanisms through which chemicals cause harm. Leveraging tools such as read-across, high-throughput screening, transcriptomics, stem-cell–based assays, and emerging computational models, researchers can now identify a chemical’s likely mode of action and select more human-relevant systems to test those hypotheses. Case studies illustrate how metabolic pathways, gene expression signatures, and structural “activity cliffs” help determine when analogs share toxicity mechanisms—or diverge in meaningful ways. Together, these advances support more efficient, ethical, and mechanistically informed assessments that can reduce reliance on animal testing while improving the prediction of human developmental risk.

Daston et al., 2025. Hypothesis-driven approach to developmental toxicity assessment: Using mechanistic information to inform testing. Reproductive Toxicology. https://doi.org/10.1016/j.reprotox.2025.109119

Fig. 1. Adverse Impacts on Physiological Systems. The diagram highlights a few examples of where exposure to an exogenous agent(s) can impact important biological processes resulting in negative impacts on the system. Exposure variables include things such as the route, dose, timing, and frequency, with each variable potentially changing molecular or early events (left side) that can advance to downstream impacts on key events (right side) leading to significant impacts on a physiological system.

The HESI Genetic Toxicology Technical Committee Germ Cell Working Group tackled this question in their latest publication, exploring whether measuring chemical levels in the bloodstream is enough to predict genetic damage in germ cells—the cells that pass genetic information to offspring.

Using data from multiple animal studies, the team compared chemicals known to cause mutations in somatic (non-reproductive) cells with their effects in germ cells. The findings: blood concentration alone does not reliably predict germ cell genetic damage.

Some chemicals caused mutations at low blood concentrations, while others showed no germ cell effects even at higher exposures. This variability underscores the continued need for germ cell-specific methods to directly assess DNA interaction, instead of relying solely on somatic cell data or systemic exposure measurements.

➡️ Read the full article here: Godschalk et al., 2025. An evaluation of the utility of blood concentration of somatic mutagens to inform germ cell mutagenic hazard. Regulatory Toxicology and Pharmacology. https://doi.org/10.1016/j.yrtph.2025.105989

The Botanical Safety Consortium (BSC) has released a timely new study as part of its Global Outreach Program: “An exploratory evaluation of the interaction risk between herbal products and pharmaceutical medicines used concurrently for disease management in Blantyre, Malawi.”

This work was led by researchers at Kamuzu University of Health Sciences with input from the BSC’s Pharmacognosy Group.

In Malawi and many other regions, traditional herbal medicine is commonly used for treatment of disease or for wellbeing. However, concurrent use of herbal and pharmaceutical products can pose safety risks due to potential interactions—especially for individuals managing chronic diseases.

A survey of 300 patients taking both herbal medicines and pharmaceuticals was conducted in Blantyre, Malawi. Using these results, the authors explored existing literature to identify potential herbal-drug interactions.

Results from this exploratory study serve as a foundation for future hypothesis-driven research studies. Investigating herbal-drug interactions, especially those involving understudied herbal products, remains a key priority, both globally and in Malawi. The approach is designed to support locally relevant, science-based health guidance that respects traditional practices while promoting patient safety.

🔗 Read the full article: Nyirenda et al., 2025. An exploratory evaluation of the interaction risk between herbal products and pharmaceutical medicines used concurrently for disease management in Blantyre, Malawi. Pharmaceutical Biology. https://doi.org/10.1080/13880209.2025.2586351

Thrombotic complications such as myocardial infarction, stroke, and venous thromboembolism remain a major cause of late-stage drug attrition, yet standard nonclinical coagulation panels are primarily optimized to detect bleeding risk rather than hypercoagulability. In this new Toxicologic Pathology article from the HESI Cardiac Safety Committee’s Biomarkers Working Group, Brooks et al. systematically evaluate a suite of hemostatic biomarkers in rat models of tissue factor–driven hypercoagulability (thromboplastin infusion) and impaired fibrinolysis (oral tranexamic acid). The study demonstrates that markers such as D-dimer, thrombin–antithrombin (TAT) complexes, plasminogen activator inhibitor-1 (PAI-1), Factor VIIa activity, and a kinetic turbidimetric fibrinolysis assay are substantially more sensitive to early prothrombotic imbalance than traditional APTT/PT/fibrinogen measures, and that distinct biomarker patterns can differentiate hypercoagulable versus hypofibrinolytic states. These findings support the use of customized, mechanism-informed biomarker panels to detect early drug-induced prothrombotic states in nonclinical species and to better de-risk compounds before they enter the clinic.

This work exemplifies HESI Global’s mission to collaboratively identify and help resolve global health and environmental challenges by bringing together scientists from academia, government, industry, NGOs, and other partners to develop practical, translational tools that strengthen drug safety assessment worldwide.

Read the full article here: Brooks et al., 2025. Evaluation of Biomarkers to Detect Early Prothrombotic Imbalance in Rat Models of Hypercoagulability Induced by Thromboplastin Infusion and Hypofibrinolysis Induced by Tranexamic Acid. Toxicologic Pathology. https://doi.org/10.1177/01926233251349767

Drs. Eliana Munarriz and Sandrine Deglin attended the World Water Congress in Marrakech, where Sandrine delivered an oral presentation illustrating how the RISK21 approach can be used for chemical prioritization, and Eliana presented a poster. The meeting brought together a diverse international community of experts in water management, sanitation, infrastructure, and policy, offering fresh perspectives on their intersections with public and environmental health. Discussions echoed familiar challenges, including bridging theory and practice, strengthening cross-sector collaboration, and advancing long-established frameworks such as the Water–Energy–Food–Ecosystems (WEFE) nexus, particularly informed by strong participation from the Middle East and Africa.

HESI Global’s science was prominently showcased throughout the American College of Toxicology (ACT) Annual Meeting, held November 16–19 in Phoenix, Arizona.

One of the meeting’s opening symposia, Advancing Nitrosamine Risk Assessment for Human Health Risk Assessment, held on Monday, November 17, highlighted research from across Genetic Toxicology Technical Committee’s Nitrosamine Research Project. Symposium co-chair Sheroy Minocherhomji (Eli Lilly) opened the session with an overview of HESI Global’s public–private partnership model and consortia-based scientific efforts. Timothy McGovern (White Oak Regulatory Toxicology, LLC) followed with an overview of current regulatory expectations. Co-chair Tetyana Cheairs (New York Medical College) presented ongoing efforts to improve the Enhanced Ames Test. Additional presentations included in vivo strategies by Robert Jolly (Eli Lilly), in vitro approaches by Wen Sun (Pfizer), and QSAR–QM modeling efforts to support expansion of the CPCA, presented by Kevin Cross (Instem).

The HESI Global Targeted Protein Degrader Safety (TPDS) Committee also presented two posters at the ACT Annual Meeting in Phoenix, AZ:

• Pharmaceutical Safety Considerations for Cereblon-Recruiting Targeted Protein Degraders
• Study Design Considerations for Preclinical Safety Assessment of Targeted Protein Degraders

Both posters were well-trafficked and received positive comments from meeting attendees.

Following ACT, the TPDS Committee convened its 2025 Annual Business Meeting. The meeting provided an opportunity to review progress on ongoing projects, discuss and endorse new initiatives, and strategize about the future direction of the committee. A focused session on the Cereblon Work Group reviewed and confirmed plans to launch an in vitro teratogenicity experimental project. New projects endorsed for advancement included QTc preclinical assessment and PK/PD. As the first outputs of the committee are about to be released (two publications), the group considered the potential evolution of committee scope and structure, discussed communications and outreach priorities for 2026, and addressed other business matters. The meeting reaffirmed the committee’s commitment to cross-sector collaboration to advance translational safety assessment for targeted protein degraders.

The Cell and Gene Therapy (CGT)- TRAcking, Circulation, and Safety (TRACS) Committee’s Annual Business Meeting went fully virtual this year, delivering three half-day sessions packed with science, strategy, and proof that “science without borders” is possible—even on Zoom!

Attendance was strong throughout the three sessions (~40 to 55 participants), including invited observers from external organizations, reflecting the committee’s focus on expanding networking and catalyzing future collaborations.

The meeting provided an opportunity to assess progress and learnings from 12 projects, many now in the final stages of manuscript development. With the 10th anniversary just around the corner (2026!), what better way to mark the milestone than with a set of seven articles lined up for publication to celebrate a decade of collaboration and impact?

With several projects nearing completion, the meeting held multiple opportunities to identify new project areas of high impact. Engagement was high throughout, with interactive whiteboards serving as idea incubators and live voting to help prioritize new project concepts. Over the coming months, scoping teams will begin developing some of the ideas proposed (e.g., in vivo CAR-T/engineered cells; in vivo editing; organoids for safety assessment of CGTs). This is an ideal time for new partners to join and help shape the next phase of CGT-TRACS projects! Contact HESI staff, Lucilia Mouries and Connie Chen, for more details on what’s brewing, and to learn how to get involved and/or propose your ideas.

Another key highlight was a regulatory session, featuring updates on the ICH CGT Discussion Group and candid (personal) perspectives from representatives of Health Canada, PMDA, and EMA CAT on common stakeholder questions.

Looking ahead, 2026 is shaping up to be a landmark year. We can’t thank our collaborators enough for their expertise, time, effort, and commitment over the years—and we can’t wait to see what comes next! Here’s to another year (decade?!) of collaboration, innovation, and turning safety challenges into real-world solutions!

For my final message of the year, I would like to offer thanks to all who supported HESI Global’s scientific mission in 2025. The impact, reach, synergy, and camaraderie that make HESI Global so phenomenal extend well beyond any quantitative measure. My thanks to all the incredible scientists who have given their time, expertise, energy, and vision when those elements are in great demand.

The need for safe environments to advance and communicate rigorous safety science may be greater now than at any time in my 25-year tenure with HESI Global. I am proud that we remain committed to this core function.

Thank you for being part of it and for standing up for science for a safer, more sustainable world.

Syril Pettit, DrPH, MEM
HESI Global Executive Director