Wednesday, September 17, 2025 9/17/2025

Decoding the metabolic requirements for vertebrate appendage regeneration

Award Number: R01GM148490
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Decoding the metabolic requirements for vertebrate appendage regeneration - SUMMARY In contrast to humans, some animals are able to scarlessly heal and regrow lost appendages after major injury. Appendage regeneration requires rapid and carefully regulated cell proliferation to replace lost tissue, an inherently anabolic process. Despite the fundamental need for biosynthesis as part of regenerative healing, we lack a mechanistic understanding of how injury is coupled to metabolic changes that enable cell proliferation and growth. Re-creating the metabolic conditions that enable growth is critical to being able to foster regenerative success in organisms where it is normally limited, such as ourselves. In this proposal, we leverage two advantages to articulate the metabolic requirements for vertebrate appendage regeneration. The first is a suite of mechanistic insights from other highly proliferative cell types, which rely on aerobic glycolysis to convert glucose to glucose-6-phosphate, a versatile biosynthetic precursor for nucleotide and phospholipid production. Our preliminary data suggest that this is a shared strategy in appendage regeneration. The second is the unique context-specificity of appendage regeneration in Xenopus tadpoles, which is lost or gained on the basis of nutrient source, developmental stage, and appendage type. This context specificity gives us the opportunity to directly compare regenerative structures to their non-regenerative counterparts and to other non- regenerative structures, thereby defining the specific features of the metabolic landscape that enhance or limit regenerative outcome. In this proposal we will test the central hypothesis that regenerative success is dictated by the ability of tissues to rapidly remodel their metabolic landscape and funnel nutrients toward biosynthesis. We will test this hypothesis by first defining the metabolic paradigm that dominates in regenerative conditions: glycolysis, pentose phosphate pathway, or oxidative phosphorylation. We will then identify shared and context- specific features of metabolic reprogramming, contrasting the metabolic profile of regenerative structures and non-regenerative structures at different developmental stages of the Xenopus tadpole. We conclude by building a regulatory landscape of metabolism in regeneration, functionally testing candidate regulatory transcription factors, and defining how metabolic gene expression is partitioned or integrated between cell types.


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 = $420,235 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	3	8/8/2025	NON-COMPETING CONTINUATION	$42,023
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	3	11/27/2024	NON-COMPETING CONTINUATION	$378,212
														Subtotal = $420,235

Issue Date FY: 2024 ( Subtotal = $420,350 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	2	11/28/2023	NON-COMPETING CONTINUATION	$378,315
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	2	7/23/2024	NON-COMPETING CONTINUATION	$42,035
														Subtotal = $420,350

Issue Date FY: 2023 ( Subtotal = $419,271 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	12/30/2022	NEW	$419,271
														Subtotal = $419,271

Grand Total All Awards = $1,259,856

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Decoding the metabolic requirements for vertebrate appendage regeneration

Award Number: R01GM148490

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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