Deciphering the myofibroblast life cycle in skin wound healing
Active Project Grant Awarded Last action
- Award ID
- F32AR083823
- Recipient
-
Oklahoma Medical Research Foundation UEI NGCNCJ1X6XA4
- Awarding agency
-
National Insititue of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $393,472
Award facts
- Assistance listing
- 93.846 Arthritis, Musculoskeletal and Skin Diseases Research
- Completion date 83% complete
- Place of performance
- Oklahoma City, OK 73104, USA
Award details come from USAspending.gov.
Description
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $1,356 | |
| Amendment | $83,224 | |
| Amendment | $1,284 | |
| Amendment | $1,284 | |
| Amendment | $79,756 | |
| Amendment | $5,284 | |
| Amendment | $5,284 | |
| Amendment | $72,000 | |
| Amendment | $72,000 | |
| Amendment | $0 | |
| Amendment | $72,000 | |
| Original award | $0 |
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Quick answers
Who received award F32AR083823?
F32AR083823 was awarded to Oklahoma Medical Research Foundation by National Insititue of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health) on September 1, 2024.
How much is award F32AR083823 worth?
$393,472 has been obligated on F32AR083823.
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