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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R01ES034387&format=word)
| Principal Investigator: Jordt, Sven-Eric | |
|---|---|
| Institute Receiving Award | Duke University |
| Location | Durham, NC |
| Grant Number | R01ES034387 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 02 Sep 2022 to 31 Aug 2025 |
| DESCRIPTION (provided by applicant): | Reactive chemicals such as chlorine and phosgene pose a grave threat to respiratory health. These agents were used in warfare, with a significant risk of diversion for terrorist attacks, and frequently cause injuries due to accidental release. Little progress has been made in developing countermeasures, with supportive treatment remaining standard of care. In this application, we hypothesize that inhalation of chlorine and phosgene damage different subsets of pulmonary cells critical for maintenance of epithelial and endothelial barriers, gas exchange, and tissue recovery. Our hypothesis is based on preliminary studies in rodent and porcine chlorine exposure models in which we discovered a novel lung repair mechanism relying on submucosal lung cells that repopulate and differentiate into new epithelia. In contrast to chlorine, phosgene initially spares upper airway cells and primarily damages pulmonary endothelial cells, including newly discovered alveolar endothelial cell subtypes, specialized aerocytes (“aCap”) and general capillary (“gCap”). Comparing mice and pigs, we noted that the identity and location of cell populations in the pig lung more closely resemble the human anatomy. The following specific aims are designed to comprehensively analyze the short- and long-term effects of chlorine and phosgene on lung cell populations in rodents and pigs: Aim 1. Monitor molecular identities and temporal dynamics of pulmonary cell populations after exposures to chlorine or phosgene and during recovery; Aim 2. Visualize pulmonary epithelial and alveolar cells and structures after chlorine or phosgene injury using thick slice microscopy; Aim 3. Compare effects of ventilator and oxygenation support and positional maneuvers on pulmonary cell survival after phosgene or chlorine exposure |
| Science Code(s)/Area of Science(s) |
Primary: 37 - Counter-Terrorism Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | See publications associated with this Grant. |
| Program Officer | Srikanth Nadadur |