Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids
NCI - National Cancer Institute
About This Grant
SUMMARY/ABSTRACT Cranial radiotherapy remains a cornerstone for treating primary and metastatic brain tumors. However, it is frequently associated with long-term cognitive decline, particularly in patients who survive beyond six months post-treatment. Despite advances in radiation delivery and neuroprotective strategies, no effective interventions currently exist to prevent or reverse radiation-induced neurotoxicity. The studies outlined in this proposal are based on a novel hypothesis that radiation disrupts neural lineage commitment in the developing human brain, driving aberrant cellular plasticity and transdifferentiation of neural stem/progenitor cells into endothelial-like phenotypes, which is supported by preliminary and published data. These fate shifts impair neurodevelopment and alter synaptic function, contributing to long-term cognitive deficits. The overall hypothesis is that radiation-induced cellular reprogramming in the human brain alters both cellular identity and functional connectivity, and that these effects can be mitigated through targeted inhibition of endothelial-inductive pathways (e.g., VEGF, FGFR, Notch). To test this, we will use mature human iPSC-derived cortical organoids subjected to fractionated radiation and apply single-cell and spatial transcriptomic approaches to define lineage transitions (Aim 1), followed by functional assays including calcium imaging and multielectrode array recordings to assess neural network activity in the presence and absence of pathway inhibition (Aim 2). This R21 project leverages cutting-edge 3D human brain models and state-of-the-art technologies to address a major gap in understanding the cellular mechanisms underlying radiation-induced cognitive impairment. Because the targeted pathways have existing pharmacologic inhibitors already in clinical use, this research has high translational potential for developing radiation mitigators to preserve brain function in cancer patients undergoing radiotherapy.
Grant Summary
Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids is a NCI - National Cancer Institute grant providing up to $368K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $368K
2028-05-31
- 1Confirm your organization is eligible for Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids from NCI - National Cancer 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.
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Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids: Frequently Asked Questions
Who is eligible for the Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids?
Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids is offered by NCI - National Cancer 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 Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids provide?
Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids provides up to $368K per award from NCI - National Cancer 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 Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids deadline?
Applications for Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids?
To apply for Radiation-induced fate shift of neural progenitors toward endothelial-like cells in human cortical organoids, 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 NCI - National Cancer Institute.