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Interrogating mechanisms of limb regeneration using a viral toolbox for molecular gain- and loss-of-function

Award Number: R21HD119496
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Interrogating mechanisms of limb regeneration using a viral toolbox for molecular gain- and loss-of-function - Project Summary Incomplete healing and limb loss impact millions of Americans each year. However, animals such as the Mexican axolotl salamander (Ambystoma mexicanum) have an exceptional ability to regenerate complex organs and tissues, including full limbs. Understanding the molecular mechanisms that make regeneration possible in the axolotl has the potential to advance therapies for improved human healing and tissue regeneration. An integral component of regeneration is the potential for contributing cells to revert back to a developmental-like state in a process called dedifferentiation. Despite its crucial role in limb regeneration, we know little about the molecular underpinnings of regenerative dedifferentiation. A key limitation to testing potential regulators of cellular dedifferentiation is a lack of tools that allow gain- or loss-of-function in complex, post-developmental limb tissue. The work outlined in this application leverages expertise in creating and applying molecular tools in the axolotl to overcome these challenges by i) validating new viral gene delivery methods in the axolotl limb and ii) combining viral delivery with novel transgenic strategies for gain-of-function, CRISPR/Cas-mediated loss-of-function, and cell type-specific nuclei isolation. Using these tools, we will test the role of a candidate transcriptional regulator in driving dedifferentiation and successful limb regrowth. The outcome of this work will not only establish new tools to elucidate mechanisms of regenerative dedifferentiation but will also provide a framework for systematic investigation of regulators of limb regeneration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $390,101 )
2025	2025	WAKE FOREST UNIVERSITY	1834 WAKE FOREST RD	WINSTON SALEM	NC	27109	FORSYTH	USA	Child Health and Human Development Extramural Research	000	1	7/23/2025	NEW	$390,101
														Subtotal = $390,101

Grand Total All Awards = $390,101

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Interrogating mechanisms of limb regeneration using a viral toolbox for molecular gain- and loss-of-function

Award Number: R21HD119496

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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