# Project 4

> **NIH NIH P42** · TEXAS A&M UNIVERSITY · 2022 · $202,989

## Abstract

Project 4 ABSTRACT
Project 4 aims to develop a translational in vitro-to-in vivo testing strategy for evaluating the inter-tissue and inter-
individual variability in responses to complex environmental exposures. This goal is a critical part of the overall
strategy of the Texas A&M University Superfund Research Center to characterize and manage the human health
risks associated with exposure to environmental emergency-mobilized hazardous substances through the
development of tools that can be used by first responders, the impacted communities, and the government
bodies involved in site management and cleanup. In the past funding period, we not only developed a multi-
tissue “biological read-across” approach for complex environmental exposures in high-content/high-throughput
assays using human induced pluripotent stem cells (iPSC), but also demonstrated its utility for quantitative
estimation of hazard of complex environmental exposures through a number of case studies that spanned
community, national and international scales. These studies show how new approach methodologies (NAMs)
can be applied for assessment of risks from real-life exposures. Our central hypothesis remains that a tiered
risk-based strategy for safety evaluation utilizing human organotypic in vitro cultures, combined with population-
based reverse toxicokinetics, can be used to accurately characterize the risks posed by combined exposures to
hazardous substances during environmental emergencies. First, we will develop a population-based human in
vitro approach to characterize inter-tissue and inter-individual variability in responses to complex environmental
exposures. We will test the hypothesis that human population-based in vitro models can refine hazard predictions
and characterize the molecular underpinnings and extent of inter-tissue and inter-individual variability. Second,
we will develop a high-throughput reverse toxicokinetics (RTK) modeling approach for complex exposures to
enable in vitro-to-in vivo extrapolation (IVIVE) of environmental samples. Because IVIVE is critical for
interpretation of in vitro NAMs data in the context of human health, we hypothesize that novel exposomic
analyses and new organ-on-a-chip models can provide concentration- and combined exposure-dependent RTK
parameters needed for IVIVE, ultimately enabling more accurate predictions of effects in vivo. Third, as art of
Center’s Disaster Research Response (DR2) approach, we will demonstrate the application of human multi-
tissue and population-wide high-throughput in vitro models to disaster research response. We will show how the
“biological read-across” method developed in the past funding period can be applied to DR2 by testing the
hypothesis that in vitro toxicity data can be used to quantitatively predict and characterize health hazard of
environmental samples. We will partner with all Projects to use their samples or collaborate on analytical,
molecular and biomedical engineering methods an...

## Key facts

- **NIH application ID:** 10349754
- **Project number:** 2P42ES027704-06
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Ivan Rusyn
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $202,989
- **Award type:** 2
- **Project period:** 2022-09-20 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349754

## Citation

> US National Institutes of Health, RePORTER application 10349754, Project 4 (2P42ES027704-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10349754. Licensed CC0.

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