Novel Tools and Approaches Research Program

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

The NTA Program will optimize durable capabilities that may already exist within DTT while introducing new capabilities that have been identified as needs and that have been shown to be valuable in other contexts, with an emphasis on those that are judged most likely to have enduring utility even with modifications/improvements over time. For example, the S1500+ high-throughput transcriptomic (HTT) platform was developed by DTT in collaboration with several partners to provide rapid characterization of expression profiles of toxicity-related genes following compound exposure, with accompanying benchmark dose (BMD) assessment. This approach has promoted an expanded understanding of mode of action and the interaction among gene signaling networks, and links exposures to adverse human health effects, thus enhancing our understanding of risk. The NTA Program focuses on promoting the development and acquisition of novel tools and approaches while balancing estimated costs (resources required) with anticipated benefits (direct benefits to DTT and indirect benefits to the field of toxicology), while also factoring in risks and likelihood of success associated with investments into specific NTAs. The NTA Program aggregates the demand emerging from other DTT program areas and facilitates efficient evaluation and use in different projects and contexts. The value of the suite of capabilities in the NTA Program is further driven by demonstrated stakeholder adoption of the NTAs and confidence in utilizing information derived from their application. The NTA Program vigorously engages both internally and externally to stay apprised of DTT internal projects/needs and seek out novel technologies on the horizon and under development in external laboratories that may be well-suited to advancing DTT goals. DTT can lead this technological transformation in toxicology due to the diversity and depth of scientific and operational expertise. DTT is uniquely positioned to lead and innovate in key areas (e.g., genomics, metabolomics, proteomics, high-throughput testing, and 3-D cellular models) because of its resources, scientific expertise over a broad range of disciplines, and international perspectives in toxicology. The NTA Program is charged with ensuring that DTTs leadership and innovation in toxicology continues, and that the data produced by DTT have direct applicability to public health problems. During FY24-25, the NTA program has continued success working on the development and use of in vitro biological model systems/assays. This included the expansion of the Tox21 assay panel for prediction of drug induced liver injury and cardiotoxicity (doi: 10.1289/EHP16190) and the use of human cerebral organoids to explore mechanisms of arsenic induced developmental neurotoxicity (DOI: 10.1016/j.taap.2025.117230). Additionally, results were reported during FY24-25 on using in vitro skin sensitization assay to investigate chemicals of concern (https://doi.org/10.22427/NICEATM-06). The NTA Program has also continued to focus on advancing new tools for example focusing on how duplex sequencing can be useful for regulatory decision making (doi: 10.1021/acs.est.4c07236).