# Project 2

> **NIH NIH P42** · TEXAS A&M UNIVERSITY · 2022 · $221,890

## Abstract

Project 2 ABSTRACT
Project 2 is a new Biomedical Research Project aimed at developing novel tools to rapidly characterize pediatric
respiratory health risks from exposure to hazardous volatile organic compounds (VOCs). This work will be a
critical element in 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. Current toxicity testing strategies do not account for developmental stage that is representative of
the pediatric lung or encompass human population variability, even though these factors (i.e., age, sex, race,
and genetics) are critical in asthma risk. Moreover, mechanisms of action underlying individual/combined VOCs
on asthma pathogenesis is poorly understood. To support the evaluation of hazardous VOCs, including real
urban mixtures, and elucidate mechanistic linkages, Project 2 will test the hypothesis that the pediatric airway is
distinctly susceptible to pulmonary injury from hazardous VOCs, and that airway responses are modulated by
extracellular vesicle (EV)-mediated signaling. The research team brings together a toxicologist, a physician-
scientist and an atmospheric chemist to address the following specific aims. Aim 1 prioritizes the evaluation of
20 individual Superfund-priority VOCs to test for asthma-related phenotypes in vitro, first using a respiratory
epithelial cell line (16HBE) cultured at air-liquid interface, and then in a population-based, age-appropriate model
comprised of pediatric bronchial epithelial cells from the Developing Lung Molecular Atlas Program. Next,
representative designed mixtures matching environmentally-relevant proportions of chemicals in ambient air will
be evaluated in the standard and population-based pediatric cell lines. These responses will inform aim 2
mechanistic studies, which will test the hypothesis that VOC exposures alter EV protein expression, underlying
respiratory dysfunction. It is known that inflammation and epithelial barrier function are mediated by exosomes,
a class of secreted EVs ranging from 30 to 150 nm. In aim 2, EVs derived from 16HBE cells exposed to select
VOCs/mixtures will be purified and sequenced using a high-throughput proteomics approach. Protein signatures
revealed in this model will then be validated across diverse pediatric donor cell lines. Last, the functional role of
VOC-exposed, cell-derived EVs will be evaluated using adoptive transfer experiments. In parallel to aims 1 and
2, aim 3 objectives will characterize VOC mixtures through mobile air monitoring across different locations in the
greater Houston Area during baseline and in response to environmental disasters. Additionally, to fill in gaps in
disaster-related toxicity testing, 16HBE cells will be directly exposed to ambient air onboard the mobile platform
in the field, using time-resolved measurements to drive conditional sampling of different ai...

## Key facts

- **NIH application ID:** 10349752
- **Project number:** 2P42ES027704-06
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Natalie M Johnson
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $221,890
- **Award type:** 2
- **Project period:** 2022-09-20 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349752

## Citation

> US National Institutes of Health, RePORTER application 10349752, Project 2 (2P42ES027704-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10349752. Licensed CC0.

---

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