Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease
NIEHS - National Institute of Environmental Health Sciences
About This Grant
Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease Cadmium (Cd) is a highly toxic environmental pollutant derived from natural sources such as volcanoes and wildfires, as well as anthropogenic activities including metalworking, coal-fired power plants, and military operations. Elevated levels of Cd have been found in the lungs of U.S. military personnel deployed to Iraq and Afghanistan, where it has been implicated in constrictive bronchiolitis and other serious lung disorders. Chronic occupational exposure to Cd, through activities like welding, grinding, and heating metals, can severely impair lung function and increase the risk of chronic airway diseases. Emerging evidence suggests that disruption of the circadian clock contributes significantly to the pathogenesis of chronic lung diseases. The circadian clock plays a vital role in regulating several important processes, including antioxidant defense mechanisms, epithelial- mesenchymal transition (EMT), and fibroblast-to-myofibroblast transition (FMT). These processes are essential for proper lung development, regeneration, and repair. Disruptions to the circadian rhythm can significantly impact lung health and the response to injury or environmental pollutants. The nuclear receptor REV-ERBα (encoded by NR1D1), a key circadian clock transcription factor, has been implicated in modulating FMT signaling and pulmonary fibrosis. Prior studies also indicate cell type-specific roles for circadian genes in alveolar type II (AT2) cells and lung fibroblasts in chronic lung disease progression. Preliminary data from our lab using a repeated Cd exposure model show impaired lung function, enhanced lung inflammation, and increased collagen deposition, accompanied by significantly reduced Rev-erbα expression. These changes are associated with the upregulation of pro-inflammatory and profibrotic genes and the downregulation of circadian clock genes. Myofibroblast-specific deletion of Rev-erbα leads to worsened lung function following Cd-induced lung injury. Despite these findings, the molecular mechanisms by which REV-ERBα modulates cadmium-induced chronic airway disease remain poorly understood. We hypothesize that Rev-erbα plays a critical, cell-type-specific role in regulating cadmium-induced persistent inflammation, lung function decline, circadian clock disruption, and fibrotic airway remodeling. Aim 1: Define the cell type-specific role of Rev-erbα in cadmium- induced persistent inflammation, fibrogenesis, and chronic airway disease using conditional knockout (cKO) mouse models. Aim 2: Determine whether pharmacological activation (Rev-erbα agonist SR29065) or genetic reconstitution (AAV9-Rev-erbα overexpression) can reverse cadmium-induced chronic airway disease phenotypes. Understanding how REV-ERBα modulates persistent inflammation and fibrogenesis in Cd-exposed lungs will provide novel insights into circadian clock-targeted therapies for environmentally induced chronic lung diseases.
Grant Summary
Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease is a NIEHS - National Institute of Environmental Health Sciences grant providing up to $426K for university, nonprofit, healthcare org. Applications are due 2028-05-14 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $426K
2028-05-14
- 1Confirm your organization is eligible for Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease from NIEHS - National Institute of Environmental Health Sciences, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIEHS - National Institute of Environmental Health Sciences before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIEHS - National Institute of Environmental Health Sciences's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease: Frequently Asked Questions
Who is eligible for the Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease?
Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease is offered by NIEHS - National Institute of Environmental Health Sciences and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease provide?
Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease provides up to $426K per award from NIEHS - National Institute of Environmental Health Sciences. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease deadline?
Applications for Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease are due 2028-05-14 (open). Because deadlines can change, verify the date with the funder, NIEHS - National Institute of Environmental Health Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease?
To apply for Nuclear Receptor REV-ERBα as a Novel Modulator of Cadmium-Induced Chronic Airway Disease, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIEHS - National Institute of Environmental Health Sciences.