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Deciphering the myofibroblast life cycle in skin wound healing

Award Number: F32AR083823
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Deciphering the myofibroblast life cycle in skin wound healing - PROJECT SUMMARY/ABSTRACT Myofibroblasts generate scar tissue in wound healing and most forms of organ fibrosis. Aberrant wound healing produces a large clinical burden, including deficient wound healing (dehiscence and chronic non-healing wounds) and excessive wound healing (keloids and hypertrophic scars). During wound healing, quiescent fibroblasts are activated to proliferate, migrate, and differentiate into myofibroblasts, which are critical for proper wound healing. After the wound is closed, SMApositive myofibroblasts disappear from the skin. Where do they go? Recent studies show that many myofibroblasts revert to deactivated myofibroblasts or post-contractile fibroblasts. This project begins with preliminary data showing that many PostnMerCreMer labeled skin myofibroblasts revert to a deactivated SMAnegative phenotype and persist in the lower scar long after wound closure, suggesting that survival is regulated rather than stochastic. Myofibroblasts in the lower scar express higher levels of the Hippo-regulated transcriptional cofactors YAP and TAZ compared to myofibroblasts in the upper scar. This project will create a molecular map of the myofibroblast life cycle and will test the hypothesis that myofibroblasts convert to a deactivated phenotype in late wound healing through YAP/TAZ-dependent survival. To generate a molecular map of the myofibroblast life cycle (Aim 1), the NuTRAP system will be used to isolate nuclei and translating mRNAs in vivo, specifically from cells of the fibroblast-myofibroblast lineage, at each stage of the life-cycle. Then, ATAC-seq and RNA-seq will be performed and data sets integrated to create a map of how chromatin and gene expression coordinately change as fibroblasts differentiate into myofibroblasts and then convert into deactivated myofibroblasts. scRNA-seq will also be used to characterize deactivated myofibroblast heterogeneity and to map the lineage of PostnMerCreMer labeled cells. Second, this proposal will use genetic approaches to investigate the role of Hippo-YAP/TAZ signaling in myofibroblast deactivation and survival (Aim 2). The results of this project will move the field forward by characterizing the myofibroblast life cycle in the skin and exploring the latent fibrogenic potential of deactivated myofibroblasts. This will be significant to human health because it may open the way to precisely modulate these signals as a treatment for skin fibrosis and regenerative medicine.


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: 2026 ( Subtotal = $85,864 )
2026	2026	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	3/31/2026	NON-COMPETING CONTINUATION	$1,356
2026	2026	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	3/27/2026	NON-COMPETING CONTINUATION	$83,224
2026	2025	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/26/2026	NON-COMPETING CONTINUATION	$1,284
														Subtotal = $85,864

Issue Date FY: 2025 ( Subtotal = $79,756 )
2025	2025	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/17/2025	NON-COMPETING CONTINUATION	$79,756
														Subtotal = $79,756

Issue Date FY: 2024 ( Subtotal = $77,284 )
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/6/2024	NEW	$72,000
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	5/3/2024	NEW	$5,284
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	3/6/2024	NEW	$0
														Subtotal = $77,284

Grand Total All Awards = $242,904

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Deciphering the myofibroblast life cycle in skin wound healing

Award Number: F32AR083823

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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