Reactivation of developmental signaling programs during human injury-repair
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
ABSTRACT Intestinal stem cells (ISCs) maintain and regenerate the intestinal epithelium within a specialized niche known as the crypt. In mouse models, ISCs have been shown to activate a gene expression program similar to the developing intestine, referred to as ‘fetal reversion’ or ‘developmental reprogramming’ during injury repair/regeneration. Reactivation of this program is emerging as a critical process for effective regeneration. However, whether a similar developmental program is reactivated during human intestinal repair/regeneration remains unknown. The current proposal provides preliminary data that developmental reprogramming takes place during human intestinal repair/regeneration, and aims to interrogate the functional importance of development and repair mechanisms. As preliminary data, we have identified the EGF family member EPIREGULIN (EREG) as a developmentally expressed gene/protein that is re-activated after various forms of injury in vitro. In addition, we have developed novel iPSC-derived human intestinal organoid (HIO) injury models following transplantation into immunocompromised mice to create an in vivo-like injury and observe that EREG influences growth/proliferation in this transplanted HIO (tHIO) model. Based on our preliminary data, this proposal will test the hypothesis that the human intestine reactivates a developmental gene expression program following injury, including reactivation of EREG, which is an essential regenerative pathway. Using adult tissue-derived organoids and genetically engineered iPSC-derived HIO models, we propose three aims: (1) Define the developmental role of EREG through overexpression and knockout experiments in tHIOs; (2) Investigate the role of EREG during injury repair in EREG-modified tHIOs challenged with irradiation, 5-fluorouracil and Oxaliplatin; and (3) Elucidate the mechanistic pathway of EREG action, specifically evaluating downstream targets including c-MYC activation, that are crucial for the regenerative response.
Grant Summary
Reactivation of developmental signaling programs during human injury-repair is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $651K for university, nonprofit, healthcare org. Applications are due 2030-03-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $651K
2030-03-31
- 1Confirm your organization is eligible for Reactivation of developmental signaling programs during human injury-repair from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, 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 NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Reactivation of developmental signaling programs during human injury-repair: Frequently Asked Questions
Who is eligible for the Reactivation of developmental signaling programs during human injury-repair?
Reactivation of developmental signaling programs during human injury-repair is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases 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 Reactivation of developmental signaling programs during human injury-repair provide?
Reactivation of developmental signaling programs during human injury-repair provides up to $651K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. 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 Reactivation of developmental signaling programs during human injury-repair deadline?
Applications for Reactivation of developmental signaling programs during human injury-repair are due 2030-03-31 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Reactivation of developmental signaling programs during human injury-repair?
To apply for Reactivation of developmental signaling programs during human injury-repair, 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 NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.