HESI Insights - August 2024

The HESI Genetic Toxicology Education and Science Outreach Committee is excited to announce the recipients of the 2024 Professional Development Travel Award and the inaugural Training Award.

The Professional Development Travel Award offers individuals with the opportunity to attend scientific conferences or workshops, while the Training Award supports travel for specific training programs (e.g., training courses, cross-lab training) to enhance core competencies and transferable skills. As part of this recognition, the awardees will be invited to GTTC’s 2025 Annual Meeting, where they will have the chance to engage with emerging projects and scientific advancements at HESI and to connect with industry, academic, and government experts in the genetic toxicology field.

Congratulations to all the well-deserving recipients! We wish them continued success in their scientific endeavors.

Learn more about the HESI Genetic Toxicology Technical Committee (GTTC) here.

HESI staff recently participated in a 3-day Advanced Facilitation Skills training course offered by Leadership Strategies, taking our facilitation skills to a new level! This course is built on the Effective Facilitator training we completed last year. We learned new meeting facilitation techniques, received expert feedback from our trainer, and got plenty of hands-on practice. We’re excited to implement our new techniques! If you join a HESI meeting, see if you can spot our new techniques in action!

We are excited to announce that HESI is a partner on the NC3Rs CRACK-IT Challenge “Wings of Change” initiative, which is focused on advancing acute and chronic avian non-animal models (NAMs). This collaboration aims to develop innovative and ethically responsible methods for assessing toxicity in avian species, reducing the reliance on animal testing, and enhancing the scientific rigor of avian safety assessments.

A launch webinar for the “Wings of Change” initiative will be held on Tuesday, 17 September 2024.

We invite researchers, innovators, and industry leaders to join us in solving this challenge and driving positive change in the field of toxicology.

For more details, visit NC3Rs CRACK-IT Challenge.

We are delighted to share that the HESI eSTAR committee and OASIS Consortium have received special recognition in a recent Society of Toxicology blog post. The 2024 Annual Meeting Report, featured on ToxChange, highlights the groundbreaking contributions of both groups to the field of toxicology. This acknowledgment underscores the significant impact of their ongoing efforts to advance early model applications and safety assessments. We encourage our members to read the full report here and join us in celebrating this esteemed recognition.

A new paper from the HESI Botanical Safety Consortium describes the development and validation of a novel method for quantifying the constituents in milk thistle extracts to ensure consistency and reliability in efficacy and toxicity research.

Milk thistle has been used for its purported hepatoprotective properties and other reported health benefits. Given that it is a complex mixture, there is product-to-product and even lot-to-lot variability in terms of chemical constituents and their quantification. There is a need for a reliable and validated method to chemically quantify the constituents of milk thistle extracts to ensure consistency and reproducibility across preclinical and clinical studies, ultimately leading to better health outcomes and informed consumer choices.

HESI Botanical Safety Consortium member Dr. Richard Van Breemen and his lab have developed and tested a UHPLC-MS/MS method for accurately measuring and standardizing flavonolignans in milk thistle extracts, ensuring their chemical consistency and authenticity for reliable use in studies. This analysis was determined to be fit-for-purpose for use in the chemical standardization of milk thistle extracts intended for preclinical and clinical investigation.

Read the full paper here:
Chemical Standardization of Milk Thistle (Silybum marianum L.) Extract Using UHPLC-MS/MS and the Method of Standard Addition. Muchiri et al., 2024. Journal of the American Society for Mass Spectrometry. https://doi.org/10.1021/jasms.4c00125

The HESI CT-TRACS Committee is pleased to announce the release of its latest publication titled “Detection of Residual Pluripotent Stem Cells in Cell Therapy Products Utilizing Droplet Digital PCR: An International Multisite Evaluation Study” in Stem Cells Translational Medicine.

This study addresses a critical safety concern in regenerative medicine—the presence of residual undifferentiated pluripotent stem cells (PSCs) in cell therapy products (CTPs), which poses a risk of tumor formation. The research highlights the successful application of droplet digital PCR (ddPCR) as a highly sensitive and robust method for detecting these impurities.

Key takeaways from the study include:

• The ddPCR method showed exceptional sensitivity, detecting as low as 0.0003% of residual iPSCs in CTPs.
• The study confirmed the reliability and reproducibility of ddPCR across multiple international laboratories.
• This approach is expected to significantly enhance the safety and quality control of PSC-derived therapies, ensuring better outcomes in clinical applications.

This publication marks a significant advancement in the field of regenerative medicine, providing a standardized method that can be widely adopted to improve the safety of cell-based therapies.

Read the full paper at the link below:
Detection of residual pluripotent stem cells in cell therapy products utilizing droplet digital PCR: an international multisite evaluation study. Yasuda et. al., (2024). STEM CELLS Translational Medicine. https://doi.org/10.1093/stcltm/szae058

The HESI Cardiac Safety Committee is excited to announce the publication of its latest study titled “Detection of Contractility Changes in the Heart from Arterial Blood Pressure Data Using Symmetric Projection Attractor Reconstruction” in the Journal of Pharmacological and Toxicological Methods.

This innovative study addresses a critical challenge in cardiovascular safety assessment—detecting drug-induced changes in cardiac contractility. Traditionally, left ventricular pressure (LVP) measurements, which are invasive and resource-intensive, have been the gold standard. However, this study introduces a novel method using Symmetric Projection Attractor Reconstruction (SPAR) to analyze arterial blood pressure (BP) signals as a non-invasive surrogate for LVP.

Key takeaways from the study include:

• The SPAR method demonstrated a high correlation (≥0.8) with LVP measurements, outperforming conventional BP metrics across various drugs and doses.
• This technique offers a less invasive, more efficient approach to screen for potential cardiotoxicity in non-clinical drug development, potentially reducing the need for direct LVP measurements.
• The findings suggest that SPAR analysis could become a valuable tool in early-stage drug development, enhancing the safety and efficiency of cardiovascular assessments.

This publication marks a significant advancement in the field, offering a promising alternative to traditional methods and aligning with the goals of reducing animal testing and improving data reproducibility.

Read the full paper at the link below:
Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction. Bonet-Luz et al., 2024. Journal of Pharmacological and Toxicological Methods. https://doi.org/10.1016/j.vascn.2024.107546

The HESI Botanical Safety Consortium (BSC) hosted a training course titled “Cultivating Safety: Toxicology 101 of Botanicals and Natural Products” on Saturday, 13 July, at the International Congress on Natural Products Research (ICNPR) in Krakow, Poland. The course was designed for experts in natural products, analytical chemistry, and pharmacognosy to gain a foundational understanding of toxicology. The 39 participants attended 1.5 hours of lectures followed by 1.5 hours of hands-on case studies to apply their knowledge. The BSC plans to offer this course at other venues in the future!

Additionally, the BSC presented a poster outlining the overall strategy of the Consortium during the meeting.

Learn more about the HESI Botanical Safety Consortium here.

HESI Program Manager, Raechel Puglisi, will be presenting virtually at ACS FALL 2024 on Monday, August 19th at 10:05 AM MST. Register here.

DIVISION: Division of Agrochemicals
SESSION: Getting Out of the Toxicology Rat Race: Development to Adoption of New Approach Methodologies (NAMs)
TALK TITLE: Transforming the evaluation of agrochemicals: Conceptualizing the problem to create a solution.
ROOM: Virtual

Learn more about the HESI Transforming the Evaluation of Agrochemical Committee here.

The Applied Genetic Toxicology (AGT) Special Interest Group (SIG) will be holding a webinar, “Meet your Peers and Explore the Diversity of our Research Field”. The webinar aims to provide a platform for students to connect with accomplished researchers, gain insights into the latest advancements in genetic toxicology and become more integrated in the EMGS community. Several speakers will be sharing about the work and professional stories, including HESI’s own Connie Chen. Online registration is open through 30 August here.

Science from the HESI Genetic Toxicology (GTTC) and Emerging Systems Toxicology for the Assessment of Risk (eSTAR) committees will be well represented at the 55th Annual Meeting of the Environmental Mutagenesis and Genomics Society (EMGS) in Palm Springs, California.

Reach out to Connie Chen or Raechel Puglisi if you have any questions!

Saturday September 7

• Workshop 1 “Sequencing the Future: Understanding Error-Corrected Sequencing” is organized by Connie Chen & Meagan Myers. Shaofei Zhang (Pfizer) will be presenting work from GTTC and Alberto del Rio (GentiBio) will be presenting work for CT-TRACS.

Sunday September 8

• Symposium 2: Towards the development of a global genotoxocity AOP network will feature several GTTC speakers and activities – Wen Sun (Pfizer) will present on Topoisomerase II and Dan Roberts (Toxys) will present on Tubulin and Kinase inhibitors.

Monday September 9

• Poster Session 2: Understanding the Carcinogenic Potential of Nitrosamines: Developing an In vivo Verification Strategy for the Ames, Comparative Analysis of In Vitro/In Vivo Mutagenicity Testing for NDSRIs presented by Tetyana Cheairs on behalf of the HESI GTTC Nitrosamine Research Program.
• Poster Session 2: Optimizing the Ames Assay for Nitrosamine Testing: Concordance Results of a HESI Multi-Sector Ring Trial presented by Tetyana Cheairs on behalf of the HESI GTTC Nitrosamine Research Program.

Tuesday, September 10

• Symposium 9: Under the Spotlight: High-Profile Chemicals will feature an overview of the HESI GTTC Nitrosamine Research Program presented by Tetyana Cheairs (NYMC).
• Platform 3: Sequencing the Genome and Beyond will include a presentation by Shaofei Zhang (Pfizer) on the GTTC reconstruction project and James Alcaraz (U Ottawa) on cancer driver gene mutations for the eSTAR committee.

Members of the HESI DART and eSTAR Committees will be in attendance at EUROTOX 2024 taking place September 8-11 in Copenhagen. Details below.

HESI Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee

• Monday, 9 September 2024, 9:30
• Poster Session P06 – A vision for the use of molecular points of departures (PODs) for chemical testing (#559)
• Karen Tilmant, Bayer

HESI CITE Lecture

• Tuesday, 10, September 2024 13:00 – 14:00
• Shana Sturla (ETH Zuerich, CH)

HESI Developmental and Reproductive Toxicology (DART) Committee

• Wednesday, 11 September 2024, 14:00 – 17:00
• Auxiliary workshop – Dose Selection for Developmental and Reproductive Toxicology (DART) Studies
• The workshop will feature Dr. Mannon Beekhuijzen, Co-Chair of the HESI DART Extended One-Generation Reproduction Toxicology Studies, who will share highlights and perspectives on the recently published “Review of Dose Setting for the Extended One-Generation Reproductive Toxicity Studies (OECD TG 443): Considerations on ECHA’s Dose Level Selection Recommendations.”
• For more information about HESI DART activities contact Shermaine Mitchell-Ryan or Connie Chen.

This year the 52nd Annual European Teratology Society Meeting will take place in Bologna, Italy. Members from the HESI Developmental and Reproductive Toxicology (DART) Committee Alternatives to the Use of Non-Human Primates for DART Studies Working Group will participate in the “DART strategies for New Therapeutic Modalities” symposium to share insights and updates from these impactful DART initiatives. This session is co-chaired by our incoming HESI DART Public Sector Committee Chair, Dr. Steven van Cruchten.

For more information about DART activities, contact Connie Chen or Shermaine Mitchell-Ryan.

The HESI Genetic Toxicology Technical Committee (GTTC) is proud to be a co-sponsor of the 52nd EEMGS and 15th ICAW Meeting meeting from September 23 – 27 in Rovinj, Croatia. GTTC will be kicking off the meeting with a pre-workshop “Where the Rubber Hits the Road: Transitioning Genotoxicity Testing from Academica to Regulatory Settings”, which will feature several GTTC members as speakers and will be co-chaired by GTTC manager, Connie Chen.

Michelle Embry, Ph.D., Deputy Director, Health and Environmental Sciences Institute (HESI), will be a featured plenary speaker at the ICCS 2024 Annual Meeting taking place in Washington, DC. Dr. Embry will discuss her work towards “one health assessment” with bioaccumulation as a learning which sits at the intersection of human and environmental health. Michelle will discuss the commonalities and differences between human and environmental health and how that has highlighted the advances and needs in next generation risk assessments (NGRA) and new approach methodologies (NAMs). Included also in her talk is the importance of problem formulation and the context regarding existing NGRA/NAMs with an emphasis on exposure and fate.

We are excited to announce the upcoming Translational Biomarkers of Neurotoxicity (NeuTox) Mini Session at this year’s Society for Neuroscience Annual Meeting in Chicago! Join us for an enlightening session titled “Seizure and Epilepsy: New Opportunities for Detection and Treatment,” featuring esteemed speaker and HESI Board member Ruth A. Roberts.

The Botanical Safety Consortium (BSC) will hold it’s first in-person meeting (with virtual option) at NIEHS in Durham, NC in October 2024. The in-person meeting is limited to members, with preference for steering committee and working group members. The virtual option will be open to all.

The hybrid portion will include updates from the working group on the new approach methodologies (NAMs) tested for their suitability for botanicals. The in-person portions will include hands-on breakout groups and discussions to understand the current tool-kit, identify gaps, and identify future research priorities. Virtual connection information will be provided at a later date, expect an email with the connection information in the coming weeks for those who register.

Register on the event page here.

We are excited to announce that the 16th Annual CHI Immunogenicity & Bioassay Summit will take place this fall in Washington, DC! This year, we are proud to have Chairs from the HESI Immuno-Safety Technical Committee’s Immunogenicity Pilot Study Project returning to share fresh insights from their ongoing research with our community.

Dr. Laurent Malherbe will be presenting an update on the collaborative HESI/AAPS effort aimed at developing a monoclonal antibody reference panel for preclinical immunogenicity risk assessment. Don’t miss this opportunity to stay informed and connect with leading experts in the field.

We look forward to seeing you there!

HESI UVCB and NextGen EcoRisk Committees will be in attendance at SETAC North America

Connect with us!

Tuesday, 22 October 2024, 10:00am

Platform Talk – 5.05.T-01 Tripartite Perspectives on Challenges and Opportunities for the Testing and Assessment of Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)
Sandrine Estelle Deglin-1, J. Samuel Arey-2, Marc Fernandez-3, Sarah A. Hughes-4, Athena Keene-5, Julie Krzykwa-1, Delina Lyon-6, Philipp Mayer-7, Claire Phillips-8, Ursula Sauer-9 and Sandrine Sourisseau-10, (1)Health and Environmental Sciences Institute (HESI), (2)Oleolytics LLC, (3)Environment and Climate Change Canada, Canada, (4)Shell Global Solutions, Houston, (5)Afton Chemical Corporation, (6)Concawe, Belgium, (7)Department of Environmental and Resource Engineering, Technical University of Denmark (DTU), Denmark, (8)Centre for Environment Fisheries and Aquaculture Sciences (Cefas), United Kingdom, (9)Scientific Consultancy – Animal Welfare, Germany, (10)TotalEnergies, France; HESI UVCBs and Multi-Constituent Substances (MCS) Committee

HESI Chaired Session – 5.05.T – Bridging the Gap Between Science Development and Policy, Regulatory, and Technology (PRT) Needs for Complex Substances – Supporting Data-Driven Decision-Making in Heath & Environmental Risk Assessment and Management.
Sandrine Estelle Deglin-1, Craig Warren Davis-2, Michael Beking-3 and Scott Coffin-4, (1)Health and Environmental Sciences Institute (HESI)(2)ExxonMobil Biomedical Sciences, Inc., Cypress(3)Environment and Climate Change Canada (ECCC), Gatineau, Canada(4)Division of Drinking Water, California State Water Resources Control Board; HESI UVCBs and Multi-Constituent Substances (MCS) Committee

Poster – 5.05.P-Tu-169 Development of a Pilot Database of Chemical Characterization Information for Substances of Unknown or Variable Composition, Complex Reaction Products or Biological Materials (UVCBs)
Erin Maloney-1, Marc Fernandez-2, Lilly Cesh-2, Antony John Williams-3, Charles Lowe-4, Emma Schymanski-5, Julie Krzykwa-6 and Sandrine Estelle Deglin-6, (1)Shell International, Netherlands, (2)Environment and Climate Change Canada, Canada, (3)Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency (US EPA), (4)U.S. Environmental Protection Agency (US EPA), (5)Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, (6)Health and Environmental Sciences Institute (HESI); HESI UVCBs and Multi-Constituent Substances (MCS) Committee

Wednesday, 23 October 2024, 1:42pm

Talk – 1.09.T-02 Optimising Concentration Setting for In Vivo Endocrine Screening Assays with Aquatic Vertebrates
Constance Mitchell, Health and Environmental Sciences Institute (HESI); HESI Next Generation Ecological Risk Committee

Thursday, 24 October 2024, 10:00am

HESI Chaired Session – 1.17.T Not Just Another NAM: Integrated, Intelligent, and Iterative Approaches to Ecological Risk Assessment
Julie Krzykwa-1, Kristin Connors-2 and Wesley S. Hunter-3, (1)HESI Global, Washington, United States(2)Procter & Gamble(3)U.S. Food and Drug Administration (FDA); HESI Next Generation Ecological Risk Committee

The HESI Developmental and Reproductive Toxicology (DART) Committee will be holding their Fall meeting virtually over two half-days. During the meeting, the committee will be hearing updates on its various working groups and consider the adoption of new ones. For more information contact Connie or Shermaine.

The HESI Cell Therapy – Tracking, Circulation, & Safety (CT-TRACS) Committee will be holding its annual meeting from 13-14 November at the HESI Offices, with an exciting opening keynote presentation will be from Dr. Bruce Levine (University of Pennsylvania). In addition to hearing the latest from existing Work Groups, the committee will be considering new project proposals and discussing new collaborations. For more information contact Lucilia or Connie.

The HESI Emerging Systems Toxicology for Assessment of Risk (eSTAR) Committee will hold it’s 2024 Annual Meeting on 13 -14 November 2024. The meeting is free, virtual and open to all!

Agenda and Meeting Link will be added closer to the date.

We are thrilled to announce that the 45th Annual American College of Toxicology Meeting will be held in Austin, Texas! Several HESI committees have organized workshops and symposia to showcase their ongoing efforts.

Immuno-Safety Technical Committee
Symposium: “Immunogenicity Risk Assessment: Are Preclinical Models Informative?”
Date & Time: Monday, November 18th, 9:00 AM – 12:00 PM CT
Chairs: Drs. Laurent Malherbe and Kristina Howard

Developmental and Reproductive Toxicology Committee
Symposium: “Informing Risk of Infertility and Adverse Pregnancy Outcomes: Are Nonhuman Primates Really Needed? (S11)”
Date & Time: Monday, November 18th, 2:00 PM – 5:00 PM CT
Chairs: Drs. Christopher Bowman and Peter J.K. van Meer

We look forward to seeing you in Austin for this exciting event!

HESI’s Committee on Transforming the Evaluation of Agrochemicals (TEA) invites you to participate in the TEA Global Challenge, a groundbreaking initiative focused on advancing ecological and human safety assessments of plant protection products using non-animal methods. This year’s challenge focuses on the safe use of a hypothetical grape fungicide (VineGuard).

Not familiar with agrochemicals? No problem! Anyone can participate!

Your mission is to propose creative solutions to evaluate the safety of VineGuard.

We offer great flexibility in how you can participate:

• You are free to choose the scope of the problem you want to solve.
• You can propose conceptual solutions (simply explain how you would proceed) or more specific solutions based on hypothetical datasets of your choice.
• You only need to explain your approach, using the provided reporting template.

Exciting Rewards:

• $2,000 USD in travel funds to attend a relevant scientific conference.
• Support from the HESI TEA committee to publish your work.

For detailed guidelines, visit TEA Global Challenge website.

Watch our recent webinar outlining the Challenge!

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.

I would like to use my platform this month to recognize the incredible expertise we have on staff at HESI. This team of outstanding scientists has training in fields including molecular epidemiology, chemistry, toxicology, public health, cancer biology, molecular biology, and genetics, among others. Of course, this training is augmented by their broad exposure to safety sciences within the HESI portfolio. Their expertise in providing scientific input, strategic leadership, and managerial coordination across nearly 100 ongoing programs at HESI is well established. But did you know that they are also sought-after scientists, educators, and strategists in their own right? HESI staff serve as invited instructors—often developing unique educational content—at academic institutions and scientific forums around the world. They are elected as leaders on local, national, and international science advisory boards and professional societies, serve as invited experts on science advisory panels, and are asked to contribute as co-authors on papers outside of their HESI programs. We are truly fortunate to have such an outstanding team that chooses to use their talents to help further HESI’s mission.

Kind regards,
Syril Pettit, DrPH, MEM, HESI Executive Director