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TGFbeta in the pathology and development of the spine

Award Number: R01AR078740
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/04/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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TGFbeta in the pathology and development of the spine - Project Summary. The long-term objective of this study is to understand signals involved in development and maintenance of the axial skeleton that can inform regenerative and engineering strategies. Members of the Tgfb superfamily are secreted signaling proteins that regulate many aspects of skeletal biology. Polymorphisms and mutations in genes that regulate Tgfb activity have been associated with pathology in the spine. It’s also been shown using genetically engineered mice that Tgfbr2 is required for development and maintenance of the fibrous tissues in the spine including the annulus fibrosus of the intervertebral disc, ligaments, and tendon. Previous results obtained in my laboratory indicate that Tgfb regulates cell fate decisions in the sclerotome, the embryonic progenitor of the connective tissues in the spine. In this application, we propose to address the instructive mechanisms whereby Tgfb regulates embryonic formation of fibrous tissues in the spine. In addition, we propose to address the problem of sclerotome resegmentation, an embryonic process that creates the spatial organization of tissues in the spine. Alterations in resegmentation would be expected to alter the context in which cells differentiate, affecting permissive signals and competence to respond to instructive signals that govern cell fate decisions. Finally, using a mouse model developed in my laboratory, we will start to determine the mechanisms of how Tgfb acts to maintain fibrous character in the postnatal annulus fibrosus. The overall aims of this proposal are to: 1) Determine the signaling pathways used by Tgfb to generate fibrous tissues of the spine during embryonic development; 2) To map the process of resegmentation and determine the mechanism of Tgfb-mediated regulation and 3) To understand how Tgfb maintains annulus fibrosus postnatally. The experiments described here will provide mechanistic information about development and maintenance of the axial skeleton and provide a foundation for future regeneration and engineering strategies in the spine.


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 = $289,363 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	7/10/2025	NON-COMPETING CONTINUATION	$289,363
														Subtotal = $289,363

Issue Date FY: 2024 ( Subtotal = $311,869 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/29/2024	NON-COMPETING CONTINUATION	$311,869
														Subtotal = $311,869

Issue Date FY: 2023 ( Subtotal = $321,514 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/4/2023	NEW	$321,514
														Subtotal = $321,514

Grand Total All Awards = $922,746

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TGFbeta in the pathology and development of the spine

Award Number: R01AR078740

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/04/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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