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The role of Fbxl22 in the regulation of skeletal muscle mass

Award Number: K01AR077684
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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The role of Fbxl22 in the regulation of skeletal muscle mass - Project Summary/Abstract Skeletal muscle atrophy occurs as a consequence of many chronic diseases and conditions such as disuse. Central to the process of muscle atrophy is protein degradation, for which the E3 ubiquitin ligases are critical in targeting specific proteins for degradation. The roles of many E3 ubiquitin ligases in muscle are unknown and specific substrates have yet to be identified. The overall objective of this proposal is to determine the role of the E3 ligase, F-box and leucine-rich repeat protein 22 (Fbxl22), in skeletal muscle atrophy. My central hypothesis is that Fbxl22 is necessary for the process of muscle atrophy. Robust preliminary data supports this hypothesis: 1) Fbxl22 mRNA expression is induced after 3 days in a model of neurogenic muscle atrophy, 2) Overexpression of Fbxl22 in hindlimb muscles results in significant elevations of total ubiquitinated proteins. I propose two specific aims: Specific Aim 1: Determine the functional role of Fbxl22 isoforms in skeletal muscle atrophy, injury and regrowth. I will address this aim using knockdown and overexpression of Fbxl22 gene isoforms in a model of neurogenic muscle atrophy and assess Fbxl22 isoform expression in an acute muscle injury model. Specific Aim 2: To identify substrate targets for Fbxl22-dependent ubiquitination. I will address this aim using a combined approach of Fbxl22 gene manipulation with proteomics analysis and post-translational modification identification of ubiquitin motifs on Fbxl22-dependent substrates. With the completion of this proposal, I expect to have identified novel mechanisms for understanding the muscle atrophy process. By identifying the mechanisms of skeletal muscle atrophy, we can explore new therapeutic strategies for improving an individual’s quality of life where muscle wasting is present. The University of Iowa has a longstanding history of support to its trainees and junior faculty. My mentor, Prof. Bodine is a world leader in skeletal muscle physiology, atrophy and hypertrophy. This K01 award will expand my research skills in ubiquitin proteomics and skeletal muscle atrophy. These tools may enable the identification of new therapeutic strategies for alleviating the detrimental impact of skeletal muscle wasting.


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 = $120,420 )
2025	2025	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/7/2025	NON-COMPETING CONTINUATION	$120,420
														Subtotal = $120,420

Issue Date FY: 2024 ( Subtotal = $120,420 )
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	5/12/2024	NON-COMPETING CONTINUATION	$120,420
2024	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	4/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$46,842
2024	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/18/2024	NON-COMPETING CONTINUATION	-$46,842
														Subtotal = $120,420

Issue Date FY: 2023 ( Subtotal = $120,420 )
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	6/19/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$120,420
2023	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $120,420

Issue Date FY: 2022 ( Subtotal = $120,420 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/1/2022	NON-COMPETING CONTINUATION	$120,420
														Subtotal = $120,420

Issue Date FY: 2021 ( Subtotal = $120,420 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/31/2021	NEW	$120,420
														Subtotal = $120,420

Grand Total All Awards = $602,100

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The role of Fbxl22 in the regulation of skeletal muscle mass

Award Number: K01AR077684

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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