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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R21ES032937&format=word)
| Principal Investigator: Salem, Aliasger K | |
|---|---|
| Institute Receiving Award | University Of Iowa |
| Location | Iowa City, IA |
| Grant Number | R21ES032937 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 06 Sep 2022 to 31 Aug 2024 |
| DESCRIPTION (provided by applicant): | Project Summary Chlorine is a chemical agent that is harmful to humans. Acute inhalation of high levels of chlorine results in the death of airway epithelial cells and leads to adverse effects on respiratory health, including airway remodeling and hyperreactivity. In a mouse chlorine exposure model, animals developed inflammation and fibrosis in large airways. This inflammation and fibrosis has been reported to be linked to damage to mitochondria and the generation of oxidative stress and reactive oxygen species. Our group has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in ROS generation in the airways. In this proposal, we will test the hypothesis that, in response to chlorine gas challenge, CaMKII contributes to the induction of hallmark features of airway inflammation. Utilizing a novel drug delivery system, we will expose mice to a CaMKII inhibitor peptide (CaMKIIN) encapsulated in PLGA NPs. These NPs will be directly delivered to the lung via oropharyngeal instillation. Furthermore, we will include a chitosan coating of the CaMKIIN-loaded PLGA-NPs to increase uptake in lung cells thereby reducing oxidative stress and fibrosis. This project will be completed by first evaluating CaMKII activation and ROS expression levels in the lungs of juvenile mice following chlorine exposure and then determining if a CaMKII inhibitor-loaded cationic nanoparticle can mitigate ROS expression and lung damage following chlorine exposure. |
| Science Code(s)/Area of Science(s) |
Primary: 37 - Counter-Terrorism Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | No publications associated with this grant |
| Program Officer | Srikanth Nadadur |