# Characterizing chemical threat agent exposures using a lung-on-a-chip platform and multi-omic analysis of common pathophysiological mechanisms

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $310,000

## Abstract

PROJECT SUMMARY
The number and variety of Highly Toxic Chemicals (HTCs) that pose a health risk to the civilian population is
extensive. The Department of Homeland Security has identified close to 200 HTCs as credible public health and
safety threats. HTCs comprise diverse chemical classes and toxicity mechanisms including acids, alkylating
agents, vesicating agents, metabolic poisons, cellular respiration inhibitors, and many with understudied toxicity
and mechanisms. However only a small subset of known HTCs have been well-characterized, and there remains
an urgent unmet need to improve our understanding of the physiological mechanisms involved in the initiation
and downstream events of injury following exposure understudied HTCs.
Relevant to this proposal, we have developed micro-physiological 3D human airway Organ Tissue Equivalent
(OTE) platform for modeling pulmonary toxicity resulting from exposure to chlorine gas and for identification of
novel mechanisms of injury and for testing of potential medical countermeasures (MCMs). Our HTC exposure
system allows safe delivery of a broad range of gas, vapor or nebulized liquid HTCs to lung OTEs with high
precision and accuracy. We have established assays rapidly determining dose/toxicity relationships,
physiologically relevant chemical, biological and functional evaluation of mechanisms of toxicity and
transcriptomic analysis for the discovery of novel toxicity pathways and MCM targets. Our overall hypothesis is
that our established airway OTE - HTC delivery system and transcriptomic bioinformatic capabilities can be
applied to different classes of HTCs to characterize mechanisms of toxicity and define potential molecular targets
for MCM intervention.
If successful, this proposal promises to improve our understanding of the initiation and downstream events of
injury on acute exposure of a broad range of understudied HTCs. Rapidly defining dose/toxicity relationships
and mechanisms of action of understudied HTCs will have a major impact on understanding potential risks for
mass HTC exposure events. Finally, the potential to identify common molecular pathways of injury in response
to a range of HTC types could have a significant impact in identifying and deploying effective medical
countermeasures with broad application across unidentified or understudied HTCs. Future work will accelerate
MCM discovery, repurposing and development with broader applicability across the pulmonary threat spectrum.

## Key facts

- **NIH application ID:** 10913409
- **Project number:** 5R01ES034416-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sean Vincent Murphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $310,000
- **Award type:** 5
- **Project period:** 2023-08-25 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913409

## Citation

> US National Institutes of Health, RePORTER application 10913409, Characterizing chemical threat agent exposures using a lung-on-a-chip platform and multi-omic analysis of common pathophysiological mechanisms (5R01ES034416-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10913409. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*