HESI Insights - October 2022

The 2022-2023 HESI Innovation Prize will recognize public sector scientists who have helped to reduce disproportionate health burdens in underserved populations and/or to promote greater health equity. Both Mid-career ($75,000 USD) and Lifetime Achievement ($25,000 USD) awards will be offered.

Interested in applying? Click here!

Applicants must submit a short letter (maximum 5 pages) that includes examples of the impact of the nominee’s work in creating novel, cross-disciplinary collaborations in relation the year’s thematic focus. Applications must also include a CV (5-10 pages maximum) for the nominee, as well as 1-2 letters of support.

Applications are being accepted from October 1 – December 15, 2022

Register now for the Immuno-Safety Technical Committee’s “Introduction to Immuno-safety Science” on-demand training course module.

This module features a collection of 16 lightening talks (~10-20mins) designed to introduce you to key concepts and tools that are essential to mastering fundamental knowledge within this discipline. All together this course will provide a comprehensive overview of the field in “bite size” digestible pieces suitable for professionals who need refresher or quick snapshot of the immuno-safety landscape to ground them in human risk and safety assessment as it pertains to agents that may modify the immune system. Register now and begin taking the course today at https://elearning.hesiglobal.org/ . Tiered pricing is available for graduate and post-doctoral trainees. Groups of 5 or more are eligible for a 20% discount, please contact Dr. Shermaine Mitchell-Ryan (smitchell-ryan@hesiglobal.org) for more information regarding the group discount rate. An Advanced course in Cancer Immunotherapies will be released in November!

Please join us in welcoming Dr. Raegan O’Lone back to the HESI staff as a Senior Program Advisor! Dr. O’Lone will work with Dr. Lucilia Mouriès on the Targeted Protein Degrader Safety Committee and other current/evolving projects and activities.

Dr. O’Lone was an Associate Director at HESI when she departed in 2017 after moving from the DC area. She started with HESI in 2008 and provided outstanding scientific and organizational leadership across a broad range of programs including the Immunotoxicology and Genomics Committees. In the intervening years, she has gained novel experiences working with academic and nonprofit institutes focused on clinical and biotech portfolios.

We are excited to welcome her back to the team (and to the DC area)! The Senior Program Advisor is a new staff role at HESI and will provide technical and strategic leadership to specific committees across our scientific programs, and in the development of novel programs.

Welcome back!

The Health and Environmental Sciences Institute (HESI) is excited about the recent news on the passing of the FDA Modernization Act 2.0 which will allow for the use of methods other than animal testing to establish a drug’s safety and effectiveness. These methods have the potential to both reduce animal use and lower the cost of developing life-saving medicines. The U.S. Food and Drug Administration (FDA) has acknowledged HESI’s role in this important endeavor and we are honored to be recognized for taking part in the 3Rs (Replacement, Reduction and Refinement) of animals in research by the FDA and many other leading safety standard organizations (e.g. OECD, EPA, JRC, etc.).

This paper, published in Global Epidemiology, summarizes five key ideas that emerged from activities of HESI’s Environmental Epidemiology for Risk Assessment Committee, formed in 2017, with a mission to understand 1) how epidemiology is used for regulation and public health guidance, 2) how to more fully utilize and leverage environmental epidemiology in quantitative human health risk assessment, and 3) how to promote greater understanding among epidemiologists of the policy process and the data it needs. These key ideas presented here could help improve how human data inform quantitative health risk assessment and decision making.

Click below to read the full article:

Considerations towards the better integration of epidemiology into quantitative risk assessment. Déglin SE, Burstyn I, Chen CL, Miller DJ, Gribble MO, Hamade AK, Chang ET, Avanasi R, Boon D, Reed J. Global Epidemiology. 9 September 2022. https://doi.org/10.1016/j.gloepi.2022.100084

This recent paper involving HESI’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee is a case study demonstrating the utility of combining the TGx-DDI biomarker and CometChip® assay to resolve conflicting genotoxicity data and provides further validation to support the reproducibility of the TGx-DDI biomarker.

Click below to read the full article:

Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChip® assay in TK6 cells. Buick JK,Rowan-Carroll A, Gagné R, Williams A, Chen R, Li HH, Fornace Jr. AJ,Chao C, Engelward BP, Frötschl R, Ellinger-Ziegelbauer H, Pettit SD, Aubrecht J and Yauk CL. Frontiers in Toxicology. 23 September 2022. https://doi.org/10.3389/ftox.2022.991590

The HESI eSTAR Committee proposes a logic framework to explore the feasibility and future development of transcriptomic methods to refine and replace the current apical endpoint-based regulatory toxicity testing paradigm.

Click below to read the full article:

A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm. Johnson KJ, Auerbach SS, Stevens T, Barton-Maclaren TS, Costa E, Currie RA, Dalmas Wilk D, Haq S, Rager JE, Reardon AJF, Wehmas L, Williams A, O’Brien J, Yauk C, LaRocca JL, Pettit S. Toxicological Sciences. 27 September 2022. https://doi.org/10.1093/toxsci/kfac097

Since many standard tests for genotoxicity need methods alterations or specific consideration for valid assessment of nanomateirals, the Genetic Toxicology Technical Committee (GTTC) has published a series of manuscripts outlining key considerations for the genotoxicity assessment of nanomaterials. These series of papers provide common considerations that can be applied to all genotoxicity testing as well as assay-specific considerations.

1. Common considerations for Genotoxicity Assessment of Nanomaterials. Elespuru et al. Frontiers in Toxicology. 24 May 2022.  DOI:10.3389/ftox.2022.859122
2. In vivo mammalian alkaline comet assay: method adapted for genotoxicity assessment of nanomaterials. Cardoso et al. Frontiers in Toxicology. 30 May 2022.  DOI:10.3389/ftox.2022.903896
3. Thymidine kinase +/0 mammalian cell mutagenicity assays for assessment of nanomaterials. Chen et al. Frontiers in Toxicology. 8 June 2022.  DOI:10.3389/ftox.2022.864753

The HESI Cardiac Safety Committee seeks Postdoctoral or Early Career Researchers working in cardiovascular safety science or a related field for the 2023 Early Career Seminar Award Series. This award offers an opportunity to share your research, learn from and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies and pharmaceutical companies.

Award: Selected candidates will receive a $500.00 USD award and be invited to present their research on a public webinar with HESI Cardiac Safety Committee scientists and other invited guests. Webinar dates will be scheduled with the awardees in Q1 2023.

Qualifications and Requirements: Eligible candidates must have a PhD or equivalent degree in biology or related field (cell biology, biochemistry, pathology, biomechanical engineering, or similar); have current post-doc position/appointment or consider themselves an early career scientist (~1-5 years post-academic training) and may not have previously received an award under this program.

Application: To apply, please send along the following: 1) completed application form, 2) CV, and 3) one reference letter to Jennifer Pierson or E’Lissa Flores at cardiacsafety@hesiglobal.org.

Deadline to Apply: 1 November 2022

Click here to download the Application Form

The HESI GTTC seeks graduate students or postdoctoral fellows working in genetic-toxicology or genomics field for a new HESI GTTC Professional Development Award. This award offers an opportunity to attend scientific conferences, workshops, or courses, etc. to build core competencies and transferrable skills, and/or share your research. Awardees will also be welcomed to attend GTTC’s Annual Meeting in May 2023 to learn about the emerging projects and science at HESI and to network with experts in the genetic toxicology field.

Award: Selected candidates will receive up to $1000.00 USD award to support attendance at relevant scientific conferences, workshops, training courses, or another related opportunity during the 2023 calendar year that contributes to professional development (e.g., laboratory visit for specialized training or another venture – please describe in the application form). Proof of attendance 30 days after such event is required to be submitted to GTTC committee.

Qualifications and Requirements: Eligible candidates must be currently enrolled in a graduate program (MS or PhD candidates) in genetic toxicology, genomics, or related field (cell biology, biochemistry, or similar) OR hold a current postdoc position/appointment (no longer than 5yrs) AND have not previously received a professional development award from the GTTC.

Application: To apply, please send along the following: 1) completed application form 2) CV or bioksketch, and 3) one reference letter from a mentor to gttc@hesiglobal.org

Deadline to Apply: 7 November 2022

Click to learn more about the HESI Genetic Toxicology Technical Committee

HESI THRIVE is a seed grant program that is innovating translational research and improving quality of life after cancer. By providing researchers with both seed funding and access to critical networks, THRIVE enhances the visibility of the patient need, the value of the research, and the reasons that larger funding entities might elect to incorporate these research streams into future funding priorities.

THRIVE provides seed grants for clinical and translational research and technology-based solutions that enhance our ability to predict when and how adverse effects may occur in patients who have received cancer treatment. The THRIVE grant program is designed to provide seed funding to investigators for the testing of initial hypotheses and collecting of preliminary data to help secure long-term funding by the National Institutes of Health (NIH) and/or other major institutions. This year, we have expanded this opportunity to accept international applications, broadening our reach and heightening the visibility of this important research area. For details on eligibility, funding, the application process, and key deadlines, please click here.

THRIVE will accept letters of intent starting 18 October 2022, and the letters of intent deadline is 10 January 2023. For more information, contact research@hesithrive.org.

HESI is seeking your suggestions for new scientific projects (human or environmental health) for consideration as an emerging issue in 2023. Proposals will be reviewed in early 2023, and one or more may be selected to form a new scientific collaborative program within HESI. Although this is not a grant, the selected program will receive support from HESI for scientific program design, coordination, and staffing.

Learn more about the HESI Emerging Issues Process on our website or download the proposal form here. The deadline to submit proposals is 12 January 2023. Don’t miss out!

HESI’s Risk Assessment in the 21st Century (RISK21) Committee presented “RISK21: A practical framework for Risk Assessment in the 21st century” as part of a free webinar series hosted by ToxGurukul on September 10th, 2022. The presentation was given by Dr. Sandrine Delgin (HESI) and Dr. Douglas Wolf (Syngenta Crop Protection). Version 2.o of the RISK21 webtool is now available and accessible here: https://risk21.org/

The Targeted Protein Degrader Committee was featured as part of a continuing education course entitled “Safety Pharmacology Considerations for Large Molecule and Novel Therapeutic Modalities”. HESI Scientific Program Manager, Connie Mitchell gave a virtual talk called “Targeted Protein Degraders: Introduction and Potential Safety Challenges”. The session was attended by over 50 people in person and additional attendees online. Other talks included the use of gene therapies and oligonucleotides as therapeutics.

The Cardiac Safety Committee also presented three posters at the SPS 2022 Annual Meeting. Two posters focused on the chronic cardiotoxicity study in the Stem Cell Working Group and the third presented results from a Subteam working on the nonclinical JTpeak endpoint to assess arrhythmic potential. Contact Jennifer Pierson for more information on either project.

On September 14, the HESI Next Generation Ecological Risk Assessment Committee hosted a webinar by Dr. Marlo Jeffries (TCU) presented ongoing research related to the Fish Embryo Toxicity Test in a talk titled Investigating the Predictive Power of Sublethal Endpoints for Fish Embryo Toxicity Tests.

The fish embryo acute toxicity (FET) test is known to be less sensitive than the fish acute test for some chemicals, including neurotoxicants. Thus, there is an interest in identifying additional endpoints that can improve FET test performance. The goal of this project was to advance alternative toxicity testing methods by determining whether select developmental abnormalities—snout-vent length, eye size, and pericardial area—are linked to adverse alterations in ecologically-relevant behaviors and delayed mortality. Fathead minnow (Pimephales promelas) FET tests were conducted with 3,4-dicholoroaniline, cadmium, and perfluorooctanesulfonic acid (PFOS) and developmental abnormalities were quantified. Surviving eleutheroembryos were reared in clean water to 14 days post fertilization (dpf), during which time behaviors and mortality were evaluated. None of the abnormalities evaluated were predictive of behavioral alterations; however, embryos with ≥14% reductions in length or ≥3.54-fold increases in pericardial area had an 80% chance of mortality by 14 dpf. When these abnormalities were used as markers of mortality, the LC50s for cadmium and PFOS were less than those calculated using only standardized FET test endpoints and similar to those obtained via larval fish tests, indicating that the snout-vent length and pericardial area warrant consideration as standard FET test endpoints.

Click to watch the full recording

On September 16th, the Developmental and Reproductive Toxicology Committee hosted a DART Fall Career Symposium. 57 people attended virtually from over 30 different colleges and universities located in the US, Africa and Asia.

HESI had a strong presence at the International Congress of Toxicology in Maastricht, Netherlands from 18-21 September 2022. Below is the list of HESI committee Sessions, Presentations and Posters at the symposium.

On September 19th, Ruth Roberts (Chair and Director of Drug Discovery, University of Birmingham, UK) gave a talk titled “Overview of Fluidic Biomarkers of CNS toxicity – The HESI Consortium Approach” on behalf of the NeuTox Committee.

On September 2oth,  Andreas Bender (Centre for Molecular Science Informatics, University of Cambridge, UK) gave a HESI CITE Lecture titled “Using chemical and biological data and AI for predictive safety and toxicology” (photo above).

On September 21st, Michelle Embry and Jos Bessems of the PBPK Committee hosted a session titled “Putting the Puzzle Together: Multiple Lines of Evidence to Inform Design and Interpretation of Long-Term, Repeated-Dose Animal Studies to Inform Human Health Risk Assessment“.

The Botanical Safety Consortium had a poster titled “New Approach Methodologies to Evaluate Botanical Safety” which was presented by Michelle Embry, HESI.

The Botanical Safety Consortium held their annual meeting fully virtual on 27 September 2022. All the talks were recorded and are available to watch on the BSC website HERE. The meeting was well attended by 360 participants. The consortium plans to have targeted in-person meetings in 2023 in conjunction with other face-to-face meetings (e.g. SOT or ICSB).

Click to learn more about the Botanical Safety Consortium

The Botanical Safety Consortium hosted a session titled “The HESI Botanical Safety Consortium’s genotoxicity testing framework – Various perspectives”at the 33rd German Society for Environmental Mutation Research Meeting (GUM) on October 6th, 2022. Speakers included Kristine Witt (NIEHS, Washington, USA), Helga Stopper (University of Würzburg, Germany) and Stefan Pfuhler (Procter and Gamble, USA).

Click to learn more about the Botanical Safety Consortium

HESI’s Developmental and Reproductive Toxicology (DART) committee will be hosting a hybrid workshop in Washington, DC, titled “Interpretation of developmental and reproductive toxicity in regulatory contexts and frameworks”. We are looking forward to welcoming more than 40 participants in-person and 70+ virtually for the two-day meeting. Highlights of the workshop will be included in the November Insights issue, with full workshop outcomes to follow in a publication. There may still be spots for both in-person or virtual attendance available. Please check the  event page here or contact Connie Chen (cchen@hesiglobal.org) for more information.

Interested in genomics, transcriptomics, and/or systems toxicology? Join us! This year the HESI Emerging Systems Toxicology for the Assessment of Risk Committee’s Annual Meeting will be fully online and open to all! The event will provide updates from the Committee’s multiple research programs covering topics from miRNAs, to error corrected sequencing, to transcriptomic-based cancer biomarkers, to the use of Cell Painting for toxicological risk characterization, and more. The entire meeting is free and open to all.

Click here to visit the Event Page and Register

The Health and Environmental Sciences Institute (HESI) & Safety Pharmacology Society (SPS) present a new, on-demand training opportunity: A closer look at the new ICH E14/S7b Q&A’s and Training Materials. The target audience includes all sponsors (small and large; other stakeholders in pharma), safety pharmacologists and toxicologists participating in the delivery of the nonclinical data, clinicians, and regulators.

This training is being provided complimentary for SPS and HESI members, and offered to nonmembers for $49.00 USD until 31 December 2022.

Click to link to training course

Contact Jennifer Pierson at jpierson@hesiglobal.org for details.

I have been with the HESI organization for almost 23 (!) years now. One of the greatest transformations I have observed has been HESI’s increasing success as a recipient of government and foundation-funded grants. It has been incredibly exciting and rewarding to see how many programs are currently receiving and/or pursuing novel grant funding for work via HESI programs. Topics funded by grants to HESI currently range from in vitro methods to characterize the mechanism of action of dietary botanicals, to standardizing methods for the use of induced pluripotent stem cells-derived cardiomyocytes for drug safety testing, to defining adverse outcome pathways, to novel methods for characterizing genotoxicity. These grants have helped to expand the resources as well as the topical and partnership reach of the HESI organization in important and impactful ways. Many thanks to all who have worked so hard to procure these grants, to the many public and private sector partners who execute the research, and the leadership of HESI’s scientific staff and volunteer chairs! If you’d like to learn more about HESI’s grant-funded portfolio and/or how to partner with HESI on a grant application, please contact jpierson@hesiglobal.org.

Kind Regards,

Syril Pettit, DrPH, MEM, HESI Executive Director