ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD
About This Grant
Project Summary Lung respiratory diseases remain a leading cause of global morbidity and mortality, often linked to impaired alveolar repair and regeneration. Severe forms of interstitial lung diseases (ILDs) and idiopathic pulmonary fibrosis (IPF) emerge when alveolar cells fail to mount effective responses to repeat lung injury, resulting in excessive extracellular matrix (ECM) deposition, fibrotic tissue scarring, and loss of alveolar type 1 (AT1) cells. While AT1 cells are essential for gas exchange, their role in lung remodeling and fibrosis is not well understood. Alveolar type 2 (AT2) cells, the primary alveolar progenitor stem cells, can proliferate and differentiate to replace damaged or dead AT1 cells. In ILD, AT2 cells may become impaired, leading to the abnormal formation of a heterogeneous population of pro-fibrotic KRT8+ alveolar differentiation intermediate (ADI) cells. Our work identified the let-7 microRNA family as a key regulator that restrains excessive ADI cell formation and hinders proper AT1 differentiation. Additionally, we found that impaired let-7 activity in AT2 cells promotes the ectopic expression of pro-fibrotic oncogenes EZH2/BACH1. Our preliminary data also support the novel hypothesis that let-7 plays a pro-fibrotic signaling role in AT1 and AT2 cells through double negative feedback loop via EZH2 and BACH1. Our proposal has three specific aims: (1) to elucidate the role of the let-7/Ezh2/Bach1 axis in maintaining AT1 cell homeostasis during alveolar injury and fibrotic remodeling; (2) to investigate the contribution of the let-7/Ezh2/Bach1 feedback circuit in lung injury and fibrotic remodeling in AT2 and AT1 cells; and (3) to examine the conservation and function of LET-7/EZH2/BACH1 regulatory axis on human AT2-to-AT1 cell differentiation. This project will address a critical knowledge gap in lung repair and regeneration processes and aims to uncover new therapeutic targets for fibrotic lung diseases.
Grant Summary
ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD is a NHLBI - National Heart Lung and Blood Institute grant providing up to $1.6M for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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Up to $1.6M
2028-04-30
- 1Confirm your organization is eligible for ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD from NHLBI - National Heart Lung and Blood Institute, 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 NHLBI - National Heart Lung and Blood Institute before the deadline.
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ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD: Frequently Asked Questions
Who is eligible for the ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD?
ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD is offered by NHLBI - National Heart Lung and Blood Institute 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 ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD provide?
ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD provides up to $1.6M per award from NHLBI - National Heart Lung and Blood Institute. 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 ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD deadline?
Applications for ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NHLBI - National Heart Lung and Blood Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD?
To apply for ROLE OF LET-7/EZH2/BACH1 DOUBLE NEGATIVE FEEDBACK LOOP IN AT1/AT2 CELL INDUCED ILD, 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 NHLBI - National Heart Lung and Blood Institute.