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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R21ES036635&format=word)
| Principal Investigator: Sabo-Attwood, Tara L | |
|---|---|
| Institute Receiving Award | University Of South Carolina At Columbia |
| Location | Columbia, SC |
| Grant Number | R21ES036635 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 01 Sep 2024 to 31 Aug 2026 |
| DESCRIPTION (provided by applicant): | PROJECT SUMMARY HABs occur when colonies of algae grow out of control and negatively impact ecosystems. These blooms can produce toxins that can have detrimental effects on animals and can also make humans sick. Blooms caused by cyanobacteria (CB) in freshwater systems are prevalent across the U.S. and are expected in increase with rising water temperatures and more frequent and severe weather events. CB produce toxins, including microcystin-LR (MC-LR) and cylindrospermopsin (CYL), that are associated with acute liver and kidney toxicity after exposure through ingestion of contaminated food or water. Inhalation exposures are increasingly recognized as an important exposure route yet few studies have examined whether inhaled HAB aerosols have subacute health implications. Compared to water, atmospheric transformation of HAB components occur rapidly and tend to occur faster in air than in water. Toxins can be complexed with algal organic matter which may also aid in photooxidation. Uncovering the atmospheric aging of HAB is critical to defining inhalation exposures and associated health effects. Acute respiratory symptoms (i.e., coughing) have been documented in people near CB blooms but no studies have investigated subacute effects. Data from animal and cell studies support that classic modes of toxicity (i.e. hepatotoxicity) that rely on special transporters are not present in the lung but noted changes in immune responses have been observed. This lack of knowledge of CB aerosols and their mechanisms of action once inhaled are the basis for the research addressed in the current proposal. To address these knowledge gaps, our innovative approach will utilize a environmental chamber to produce and characterize atmospherically transformed aerosols of CB that will be applied directly to highly differentiated cultures of human primary lung cell cultures grown on an air-liquid interface supports. We will also perform novel mechanistic investigations by probing the ability of HAB-exposed lung cells to modulate critical immune cells (dendritic cells) through the production of extracellular vesicles. We will test the overall hypothesis that transformed aerosols of CB that produce the greatest extracellular ROS will trigger robust ROS and immune cellular responses evidenced by changes in epithelial cell genes, ROS production and secretion of EVs. Furthermore these EVs will modulate dendritic cells by altering their transcriptome and pushing them to a maturation state. To test this hypothesis we propose two specific aims: (1) characterization of fresh and aged algal aerosols and toxins, and (2) evaluate toxicity of aged algal aerosols and toxins to highly differentiated human lung epithelial cells and test whether released EVs alter the maturation and transcriptional profiles of dendritic cells. This work is both significant and innovative as successful completion will generate first-time toxicity profiles for airborne HABs in cell models that more closely mimic in vivo airways. In addition, data produced will provide a unique view on newly identified mechanisms of action of CB in the lung which support inhalation and pulmonary health as a risk for exposed populations. |
| Science Code(s)/Area of Science(s) |
Primary: 33 - Oceans and Human Health Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | No publications associated with this grant |
| Program Officer | Anika Dzierlenga |