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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R01ES032081&format=word)
| Principal Investigator: Kosmider, Beata | |
|---|---|
| Institute Receiving Award | Temple Univ Of The Commonwealth |
| Location | Philadelphia, PA |
| Grant Number | R01ES032081 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 10 Sep 2020 to 31 Aug 2025 |
| DESCRIPTION (provided by applicant): | Abstract Alveolar type II (ATII) cells produce and secrete pulmonary surfactant and restore the epithelium after damage. Due to their energy-demanding functions and location in the lung, they are highly dependent on mitochondria. Aerosols produced from e-cigarette devices contain both the particulate and gas phases, nicotine and flavors. The effect of flavored constituents and electronic cigarette (e-cigarette) aerosols on ATII cells is unknown. Mitochondrial DNA (mtDNA) is susceptible to damage due to the lack of histones that serve as a barrier against damaging factors. MtDNA damage can lead to mitophagy and ATII cell death. Our preliminary results demonstrate the harmful effect of e-cigarette aerosols with fruit and dessert flavors on human and murine primary ATII cells. DJ-1 has a cytoprotective role and participates in transcriptional regulation and mitochondrial function. Our hypothesis is that flavored constituents and e-cigarette aerosols with fruit and dessert flavors cause mitochondrial dysfunction due to the impairment of DJ-1 function leading to ATII cell death. In SA#1, we will determine mitochondrial dysfunction induced by flavored constituents and e-cigarette aerosols in human primary ATII cells. The mechanism of DJ-1 cytoprotective function in ATII cells will be studied in SA#2. In SA#3, we will analyze the respiratory injury risk of flavored constituents and e-cigarette aerosols in wild-type and DJ-1 KO mice. The current project will fill the gap in our knowledge on the effect of this exposure on primary ATII cells and respiratory function and can provide novel therapeutic targets for lung regeneration. |
| Science Code(s)/Area of Science(s) |
Primary: 69 - Respiratory Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | No publications associated with this grant |
| Program Officer | Frederick Tyson |