Developmental Mechanisms Driving Vascular Resiliency in the Brain
About This Grant
SUMMARY The Circle of Willis (CW) is a collateral circulatory system formed by the connection of anterior and posterior arteries to ensure oxygenated blood supply to the brain. This is especially critical in cases of arterial dysfunction, including aneurism and stroke. The anatomy of the CW is highly conserved across animal species and is formed by angiogenesis during embryonic development. Developmental and anatomical variations of the Circle of Willis are surprisingly prevalent in the human population and are associated with an increased risk of adverse outcomes from cerebrovascular diseases. However, the developmental origins and molecular pathways that lead to these structural variations remain largely unknown. This proposal aims to uncover the developmental cellular and molecular factors that underlie CW formation and maintenance. Using zebrafish, we recently found that the loss of a highly conserved microRNA, miR-125a, leads to the development an incomplete CW with absent or narrowed posterior arteries, resulting in loss of collateral function by adulthood. We identify this defect results from altered embryonic brain angiogenesis. Complementary, miR-125 suppression in human iPSC vascular organoids also causes defectous angiogenic sprouting. scRNA-seq revealed zebrafish and human miR- 125a-deficient endothelial cells exhibit enhanced mitochondrial number and oxidative metabolism due to de-repression of the PPARγ coactivator 1α (pgc1a) gene, a key regulator of mitochondrial biogenesis. These discoveries raise fundamental questions about the developmental origins of CW anatomies and their role in cerebrovascular protection: Are these variations established during embryonic development, and could they be corrected to protect against vascular stress? How does mitochondrial metabolism influence CW artery formation and stability? By addressing these questions, this proposal seeks to advance our understanding of CW development and identify potential future therapeutic targets for sustaining cerebrovascular health. 1
Grant Summary
Developmental Mechanisms Driving Vascular Resiliency in the Brain is a NHLBI - National Heart Lung and Blood Institute grant providing up to $1.7M for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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Up to $1.7M
2028-04-30
- 1Confirm your organization is eligible for Developmental Mechanisms Driving Vascular Resiliency in the Brain 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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Developmental Mechanisms Driving Vascular Resiliency in the Brain: Frequently Asked Questions
Who is eligible for the Developmental Mechanisms Driving Vascular Resiliency in the Brain?
Developmental Mechanisms Driving Vascular Resiliency in the Brain 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 Developmental Mechanisms Driving Vascular Resiliency in the Brain provide?
Developmental Mechanisms Driving Vascular Resiliency in the Brain provides up to $1.7M 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 Developmental Mechanisms Driving Vascular Resiliency in the Brain deadline?
Applications for Developmental Mechanisms Driving Vascular Resiliency in the Brain 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 Developmental Mechanisms Driving Vascular Resiliency in the Brain?
To apply for Developmental Mechanisms Driving Vascular Resiliency in the Brain, 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.