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Mechanosensation in Muscle-Resident Mesenchymal Stromal Cells during Regeneration

Award Number: F31AR087301
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: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Mechanosensation in Muscle-Resident Mesenchymal Stromal Cells during Regeneration - PROJECT SUMMARY Fibrosis and fatty infiltration impair skeletal muscle's regenerative properties and function in traumatic injuries and chronic diseases, and thus there is an urgent need for innovative therapies to restore muscle structure and function. Such muscle degenerative hallmarks are driven by muscle-resident mesenchymal stem cells, also known as fibro-adipogenic progenitors (FAPs). While these cells typically contribute to muscle regeneration by supporting myogenesis through proliferation, secretion of pro-myogenic paracrine factors, and deposition of matrix before apoptotic clearance, they can become resistant to apoptosis in chronic injuries, before differentiating into myofibroblasts and adipocytes. However, extrinsic factors controlling FAPs’ response to muscle injury are not well understood. One such factor may be the biophysical cues during muscle healing. While matrix stiffness regulates mesenchymal stromal cell fate, how FAPs sense the changing matrix stiffness and drive their function in muscle regeneration remains unknown. The mechanism of sensation may be through PIEZO1, a mechanosensitive ion channel. PIEZO1 has been shown to be present in many cells across different tissues, including cells found within muscle, and responds to a range of mechanical cues, especially substrate stiffness. However, it has not yet been identified in FAPs, nor the role PIEZO1 plays on activation. This project will elucidate how FAPs sense the mechanical changes in their environment and downstream processes of PIEZO1 activation. To address this gap, the role of PIEZO1 in mechanosensation in FAPs during muscle regeneration in vivo will be identified in Aim 1. Following conditional knockout of PIEZO1 in FAPs, the muscles will then be injured with barium chloride injection. Muscles without PIEZO1 will show worsened muscle regeneration and increased pathology. Furthermore, matrix stiffening will be prevented following muscle injury to assess the role of mechanosensation in activating PIEZO1 in vivo. Here, muscles with impaired matrix stiffening will behave similarly to those without PIEZO1, showing signs of impaired muscle regeneration and increased pathology, further implicating the importance of PIEZO1 in matrix stiffness sensation and healthy muscle regeneration. Aim 2 seeks to isolate the mechanism of PIEZO1 activation in FAPs and identify downstream effects of activation. Using engineered hydrogels to match stiffnesses that are seen during muscle regeneration, I expect stiffer hydrogels to cause increased PIEZO1 activation. Furthermore, any mediators that are downstream of PIEZO1 will be identified, with a focus on mechanotransductive genes. This project will frame the research within a clinical context and provide a multi-disciplinary training in tissue engineering and stem cell biology to build my career as a future physician-scientist as well as providing therapeutic targets to prevent the development and progression of muscle degeneration following injury.


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 = $50,114 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	5/21/2026	NEW	$0
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/14/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Mechanosensation in Muscle-Resident Mesenchymal Stromal Cells during Regeneration

Award Number: F31AR087301

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: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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