HESI Insights - December 2024

In 2024, HESI’s portfolio and scientific team continue to expand, and with this growth comes a renewed commitment to enhancing the quality and effectiveness of our program support. To strengthen this support, we’re proud to announce the establishment of three new Centers:

1. Center for Environmental and Ecological Health
2. Center for Translational Sciences
3. Center for Patient and Consumer Safety

These Centers serve as dedicated hubs for staff to share strategies, scientific insights, management practices, and innovations. Each of HESI’s Scientific Committees and Board Strategic Programs align with one of these Centers, streamlining collaboration and coordination.

We hope these Centers will help you easily identify programs related to your core interests.

We are excited to announce the following promotions as part of this new structure:

• Dr. Sandrine Deglin has been promoted from Senior Program Manager to Senior Advisor, Center for Environmental and Ecological Health (CEEH)
• Dr. Connie Chen has been promoted from Senior Program Manager to Senior Advisor, Center for Translational Sciences (CTS)
• Dr. Lucilia Mouriès has been promoted from Senior Program Manager to Senior Advisor, Center for Patient and Consumer Safety (CPCS)

Visit our HESI Centers webpage to learn more.

An OECD IATA case study on Bioaccumulation was developed by the Health and Environmental Sciences Institute (HESI), Canada, United Kingdom, United States, Business at OECD (BIAC) was recently released as part of the 2023 review cycle of the IATA Case Studies Project. This IATA combines decades of work and the most recent state of the science into a single document and approach that can be adapted to various problem contexts and data types.

• The Bioaccumulation IATA provides a systematic and transparent weight of evidence approach to aid evaluators in the collection, generation, evaluation, and integration of multiple lines of evidence for clear and transparent decision-making within defined problem contexts.
• Three illustrative case studies representing both data poor and data rich chemicals are presented
• We hope that this IATA methodology will spark the development of additional examples and serve as a guide for bioaccumulation assessments as the science and regulatory needs evolve.

If you would like additional information on the IATA or are interested in working through case studies using the approach, please contact Michelle Embry (membry@hesiglobal.org).

After over three decades of unwavering dedication and extraordinary contributions to HESI, our beloved Branch Administrator, Cyndi Nobles, will be retiring on December 31, 2024.

Cyndi joined HESI in 1993 and has been an integral part of the organization ever since. Over the years, she has served as the primary staff administrator to the HESI Executive Director and senior staff, playing a pivotal role in coordinating many elements of HESI’s financial management as well activities with the HESI Board of Trustees, the HESI Assembly, and the Emerging Issues Committee (EIC). Her meticulous attention to detail, commitment to excellence, and deep institutional knowledge have been invaluable in advancing HESI’s mission.

In addition, Cyndi has been instrumental in supporting HESI’s Scientific Committees and the HESI Annual Conference. If you have ever attended a HESI event, chances are you’ve had the pleasure of interacting with Cyndi and know how essential she has been in making it all run smoothly.

Her warmth, professionalism, and dedication will be deeply missed by everyone who has had the privilege of working alongside her. While we are sad to see her leave, we celebrate her incredible career and extend our heartfelt gratitude for all she has done for HESI.

Please join us in wishing Cyndi all the best in this exciting new chapter of her life!

We are excited to welcome Hannah Richardson as HESI’s new Donor Relations and Operations Manager.

In her role, Hannah will be responsible for activities that Cyndi Nobles has so capably supported for many decades (she will be retiring on December 31, 2024). These roles will include managing donor and sponsor relationships, supporting institutional operations, and overseeing financial payments as part of HESI’s mission to address global health and environmental challenges.

Hannah brings a strong background in donor engagement, organizational management, and financial oversight. Her experience includes enhancing membership retention and managing large-scale events with the American Clinical Laboratory Association, as well as mentoring young professionals with The Fund for American Studies. She holds a Bachelor’s degree in Business Administration from Viterbo University and has demonstrated leadership in operational and financial management.

We are thrilled to have Hannah on board and look forward to her contributions. Please join us in welcoming her to the HESI team!

Hannah can be reached at hrichardson@hesiglobal.org

The HESI Cardiac Safety Committee, alongside academic and industry collaborators, has published a new review article titled “An Overview of Drug-Induced Sodium Channel Blockade and Changes in Cardiac Conduction: Implications for Drug Safety” in Clinical and Translational Science. This publication addresses the critical role of sodium channel Nav1.5 in cardiac safety assessments and provides guidance for identifying and mitigating proarrhythmic risks in drug development.

Key Takeaways:

1. Understanding Nav1.5 Blockade: Drug-induced blockade of cardiac sodium channel Nav1.5 can slow cardiac conduction, increase QRS duration, and heighten proarrhythmic risks.
2.  Clinical and Regulatory Gaps: Despite its importance, there is no standardized framework for assessing conduction slowing compared to QT prolongation.
3. Methodological Advances: The review outlines in silico, in vitro, and in vivo tools for evaluating Nav1.5 block, emphasizing a “weight of evidence” approach.
4.  Translational Challenges: The article highlights species-specific differences and challenges in translating nonclinical findings to clinical outcomes.
5. Risk Mitigation Strategies: Early screening and robust biophysical characterization can improve cardiac safety predictions during drug development.

Why It Matters: This article bridges gaps in cardiac safety assessments, offering actionable insights to researchers, regulators, and drug developers. Understanding Nav1.5 pharmacology is critical for identifying and managing potential safety concerns in both cardiac and non-cardiac drugs.

Who Should Read This: Drug developers, safety pharmacologists, regulatory scientists, and anyone involved in cardiac safety assessments will benefit from this comprehensive overview.

Read the full article here: https://doi.org/10.1111/cts.70098

The challenges and opportunities for the development of regulatory T cells (Tregs) therapies to treat autoimmunity and transplantation took center stage at a workshop co-hosted by the National Institute of Allergy and Infectious Diseases (NIAID) and the Health and Environmental Sciences Institute (HESI).

Ten months in the making, the organizing committee led by Daniel Rotrosen (Director of the Division of Allergy, Immunology, and Transplantation, NIAID), Jeffrey Bluestone (CEO, Sonoma Biotherapeutics) and HESI program managers from CT-TRACS and ITC committees, designed a program that brought together leading scientists, pioneers in Treg biology, and experts in Treg therapy development, alongside regulators, to explore the scientific advances and regulatory considerations for manufacturing engineered Treg products for non-oncologic applications.

This 1.5-day event was attended by 81 in-person participants, including 30 speakers and panelists, and over 130 online participants. Notably, the workshop saw strong engagement from FDA scientists, both in person and online, including from the Director of the FDA’s Center for Biologics Evaluation and Research (CBER), Dr. Peter Marks. In his opening remarks, Dr. Marks emphasized the agency’s strong interest in advancing T regulatory (Treg) cell therapies, particularly as they intersect with genetically modified T cell technologies. He highlighted this convergence as a transformative opportunity to address chronic autoimmune diseases, which are often as debilitating as cancers but remain underserved by current therapies, and viewed this workshop as a critical platform to discuss the safe and effective clinical development of Treg therapies.

This collaborative effort underscores the importance of advancing Treg therapies to address critical unmet needs in patient care. A publication is in preparation to share key highlights and learnings from this event.

Click the links to learn more about HESI CT-TRACS and ITC committees.

On November 13, 2024, the HESI Emerging Systems Toxicology for Assessment of Risk (eSTAR) Committee Annual Meeting brought together over 100 participants from across the globe for a successful day of knowledge sharing and collaboration. This virtual meeting showcased the exciting progress of six cutting-edge omics-based projects, including:

• miRNA biomarkers
• Transcriptomic biomarkers for tumorigenicity
• Error Corrected Sequencing
• Cell Painting
• tPOD
• Carcinogenomics

Attendees also explored cross-sector initiatives such as a microphysiological systems (MPS) platform project, demonstrating the committee’s commitment to advancing systems toxicology through innovation and collaboration.

A highlight of the event was a keynote presentation by Dr. Michael Roberts, Chief Scientific Officer of the International Space Station (ISS) National Laboratory, who shared insights on “Research and Innovation from Low Earth Orbit.”

Missed the Event? Recordings of the presentations and discussions are now available! Access them here.

The Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee held its annual meeting in person and online on 14-15 November to review its portfolio of current activities within the Tumorigenicity Working Group and Point of Administration-Biodistribution Working Group. We were honored with the presence of Dr. Bruce Levine (University of Pennsylvania), who gave a keynote lecture on “Balancing Precision and Doubt: Tracking Cells and Assessing Risk”, which led into updates and discussions on the committee’s working groups aimed at advancing the safety of CAR-T therapies. The committee also reviewed two exciting project proposals aimed at expanding the remit of the committee to gene therapies (germline transmission and insertional site analysis) and a proposal to collaborate with the NIH/NHLBI on a workshop to identify the compelling questions and critical challenges related to tracking and monitoring the fate of cell therapy products in patients.

New participants interested in joining these new projects in development, and scope expansion to Gene Therapies safety are welcome and encouraged to join! Please contact the committee managers, Connie Chen and Lucilia Mouriès, for more information.

Click the link to learn more about the HESI CT-TRACS Committee.

Over 70 scientists from the UK, Europe, Canada and the US convened over two days for “The Future of Genetic Toxicology: NAMs and ecNGS,” a joint meeting between the UKEMS Industrial Genotoxicity Group and the Next Generation Sequencing Special Interest Group at the Discovery Center (DISC) AstraZeneca in Cambridge, England. During the meeting, Patricia Escobar (Merck) gave a talk on behalf of the eSTAR committee on the “Update on the use of ecNGS (Duplex Sequencing) as a potential tool to measure clonal expansion as an early tumorigenicity biomarker for non-genotoxic compounds.” Connie Chen (HESI) closed the meeting with a presentation titled “Multi-Sector Collaborations to Support Regulatory Acceptance of ecNGS.” She highlighted HESI’s pivotal role in supporting the previous publication of OECD Test Guidelines and ongoing efforts within the Genetic Toxicology Technical Committee (GTTC) to integrate ecNGS technology into existing genetic toxicology test guidelines.

Learn more about the eSTAR Committee here, and the GTTC ecNGS working group here.

HESI CT-TRACS committee collaborators, Silvana Libertini (Novartis) and Joana Ferreira (AstraZeneca), presented at the Swiss 3RCC Symposium on alternative in vitro assays for stem cell-based therapy products’ preclinical safety assessments. Tumorigenicity is a major safety concern for stem cell-based therapies, yet in vivo models are limited. The Highly Efficient Culture (HEC) assay, along with SACF and GILA assays, offers an in vitro alternative for assessing these risks in genetically modified stem cell products.

The assays featured in their talks, HEC assay, SACF, and GILA assays, were part of two CT-TRACS’ international multi-site evaluation collaborative studies. We are thrilled to see the impact of this work toward the implementation of alternative methods for safety assessment of CGT products and reducing animal use!

Learn more about the projects here: https://hesiglobal.org/cell-therapy-tracking-circulation-safety-ct-tracs/

The HESI THRIVE 2025 Seed Grant Program is now accepting Letters of Intent. This grant 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/.

SCIENTIFIC PROGRAM MANAGER

Looking for an exciting career in human or environmental toxicology, drug safety, biomedical innovation, regulatory science, epidemiology, exposure-science, and risk assessment — outside of the lab?

Want a great place to grow your career via collaboration with thought-leaders from government, industry, academia, clinic, and NGOs?

Seeking an opportunity to apply your skills in leadership and program management while applying science to real world challenges?

The Health and Environmental Sciences Institute (HESI), a global nonprofit scientific organization, seeks a Scientific Program Manager to help lead collaborative scientific programs in the biomedical and environmental health fields. Successful candidates will have a passion for fostering creative and rigorous scientific collaborations that pool expertise, resources, and technical input from a diverse base of stakeholders. HESI Scientific Managers are responsible for developing, managing, and providing scientific input to large international scientific teams that generate science to protect public health and the environment. HESI offers the opportunity to work with internationally recognized scientists from government, academia, NGOs, clinic, and industry. This responsible position requires leadership skills and the ability to work as part of a team to help realize HESI’s mission of achieving science for a safer, more sustainable world.

This position works in Washington, DC, and reports to the HESI Executive Director.

KEY RESPONSIBILITIES

Provides scientific, strategic, management, and administrative support to collaborative scientific committees involving academic, government, nonprofit, and private sector scientists;

Works with committee members to design and execute novel scientific research programs, publications, workshops, and trainings;

Prepares and monitors committee budgets, assists with communications (technical and non-technical), supports membership development, facilitates workshops and meetings, and contributes to overall HESI strategy and outreach.

QUALIFICATIONS

• A Master’s or Ph.D. in a scientific field such as toxicology, pharmacology, genetics, immunology, epidemiology, genetics, molecular biology, cell biology, pathology, chemistry, environmental health, or related life sciences and a minimum of 3 years of experience in project management, drug or chemical safety evaluation, scientific consulting, and/or regulatory affairs.
• Strong facilitation skills and the ability to work with groups meeting virtually or in person.
• Advanced written and verbal communication skills, outstanding management and organizational ability.
• At least 5 years of experience in project or program coordination.
• Leadership experience and presentation skills.
• Technical/scientific writing.

EXPERIENCE

Expertise in any/all of the following areas preferred:

• Regulatory Science
• Exposure Science
• Drug Safety Assessment
• Chemical Safety Assessment
• Computational Toxicology
• ADME

ABOUT HESI

At HESI, it is our mission to collaboratively identify and help to resolve global health and environmental challenges through the engagement of scientists from academia, government, industry, clinical practice, research institutes and NGOs. We achieve that in a variety of ways:

• Create a collaborative environment where scientists from academia, government, industry, and NGOs come together to find solutions that improve health and environmental safety.
• Encourage the development of meaningful studies that ask the right questions, structure the right framework, and develop solutions that inform decision-making by both private- and public-sector scientists.
• Create a knowledge base that can be easily transferred from the laboratory or journal page to real life.

Individuals interested in applying for this position should send their RESUME with COVER LETTER to Career@hesiglobal.org.

Principals only, please. Unsolicited resumes from third-party agencies will not be considered. Qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, or veteran status.

Learn more about us at www.hesiglobal.org.

What a tremendous and exciting year of collaboration, transformation, innovation, and impact at HESI!

Thank you, Cyndi! On behalf of the Board of Trustees, I’d like to sincerely thank Cyndi Nobles and extend our warmest well wishes as she retires! Her dedication to advancing HESI’s mission has been unmistakable. Cyndi leaves with us an extraordinary three-decade legacy, as she provided invaluable contributions to every aspect of HESI’s evolution and impact. Wishing you a happy retirement and all the best as you write the next chapter of your journey. Congratulations and thank you for all you have done for HESI, Cyndi!!

HESI is growing and building capacity and capability. One recent example is the addition of Hannah Richardson, who joined HESI as our new Donor Relations and Operations Manager. Hannah will play a key role in strengthening donor engagement and operational management. On behalf of the Board of Trustees, I’d like to warmly welcome you, Hannah! Thank you in advance for all you will help shape and transform for HESI.

HESI is committed to leader development and strategic evolution. On behalf of the Board of Trustees, I’d like to highlight the well-deserved promotions of Dr. Sandrine Deglin, Dr. Connie Chen, and Dr. Lucilia Mouriès. I can’t wait to see how you all stimulate HESI’s evolution as you lead the new HESI Centers. The Centers will serve as hubs to streamline collaboration and enhance support for scientific committees, aligning with HESI’s commitment to innovation and excellence.

The impact of HESI’s collaborative science is remarkable and unmistakable. Too many to highlight in this short write-up…but just to mention a couple, I’d like to highlight the release of the OECD IATA case study on bioaccumulation – a key milestone highlighting how HESI drives collaborative approaches to advance scientific methodologies and regulatory frameworks. Please also join me in celebrating the success of the NIAID/HESI Treg therapies workshop, which showcases HESI’s leadership in cutting-edge research and collaboration.

HESI THRIVE has real impact. If, unfortunately, you or anyone you care about has had cancer treatment, I encourage you to please become familiar with the objectives, intent, and impact of HESI THRIVE. Please also consider sharing with your networks the notice found in this newsletter about the HESI THRIVE Grant and open call for Letters of Intent. THRIVE, like all HESI’s areas of science focus, underscores HESI’s commitment to supporting innovative research with real-world implementable science that has real impact.

Exciting evolution ahead! As 2024 draws to a close and as we anticipate the amazing impact HESI will have in 2025, I want to thank the HESI staff, volunteers in the scientific committees, partners, stakeholders, and board members for your collaborative approach and innovative drive over the past year. As HESI continues to evolve, we aim to ensure HESI continues to have an unrivaled role as a leader in fostering collaborative science for public health and environmental safety.

I encourage you all to stay engaged and in touch with us to help shape our future together, navigating an exciting period focused on deeper collaboration, transformation, innovation, and impact.

Please have a safe and happy holiday season and New Year.

Warm regards,

Gary

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