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Investigating the role of FGF21 in bone homeostasis in Duchenne Muscular Dystrophy

Award Number: F30HD118663
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Investigating the role of FGF21 in bone homeostasis in Duchenne Muscular Dystrophy - PROJECT SUMMARY/ABSTRACT Duchenne Muscular Dystrophy (DMD) is a severe muscle-wasting disease caused by mutations in the dystrophin gene (DMD). Beyond the characteristic muscle wasting, patients with DMD are often plagued by significant skeletal comorbidities, including severe osteoporosis and consequent fracture. Although an estimated 60% of patients are affected by these comorbidities, there are no recommended prophylactic treatments. This is partially due to poor understanding of the pathogenesis of osteoporosis in DMD. Osteoporosis results when bone resorption by osteoclasts outweighs bone deposition by osteoblasts. Our lab has identified a novel myokine, fibroblast growth factor 21 (FGF21), which is increased in the serum of DMD patients and mouse models. Neutralization of FGF21 prevented osteoporosis in a mouse model by reducing the number of osteoclasts. Furthermore, in vitro studies demonstrated that FGF21 directly promotes osteoclastogenesis. However, the mechanism of FGF21 signaling to osteoclasts remains unknown. Aim 1 will investigate the role of FGF21 signaling to osteoclasts in bone homeostasis in a mouse model of DMD by using osteoclast-specific FGF21 receptor knockout mice. Aim 2 will explore how FGF21 potentiates osteoclastogenesis by evaluating signaling mechanisms and the effect on precursor fusion, an essential step in differentiation. Since preliminary data also suggest that FGF21 promotes osteoclast activity, Aim 3 will examine how FGF21 affects secretion of bone-resorptive proteins via the lysosome. These carefully and rigorously designed studies will provide valuable insight into how FGF21 promotes osteoporosis in DMD and advance our understanding of osteoclast biology. Successful completion of this project will establish FGF21 as a critical regulator of bone homeostasis and a promising target for treatment of osteoporosis in this patient population. The project and training plan described herein were developed specifically for Ms. Hurley-Novatny. The experiences, skills, mentoring, and topics of this proposal were designed to ensure that Ms. Hurley-Novatny achieves her training goals and becomes a successful, independent physician-scientist in the field of orthopedics and bone research. Under the guidance of Dr. Hongshuai Li and Dr. Matthew Potthoff, Ms. Hurley- Novatny will receive the mentorship she needs to develop as a scientist and the technical training to become a researcher in musculoskeletal biology. The MSTP, Department of Orthopedics, and Department of Anatomy and Cell Biology provide ample training opportunities in the form of seminars, collaborations, opportunities to present research, and research support both financially and otherwise. The University of Iowa has an unparalleled history of research in the field of orthopedics, providing Ms. Hurley-Novatny a unique training environment to achieve her goal of becoming a surgeon-scientist in the field of orthopedics at a major academic medical center.


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 = $47,092 )
2026	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Child Health and Human Development Extramural Research	000	2	5/7/2026	NON-COMPETING CONTINUATION	$47,092
														Subtotal = $47,092

Issue Date FY: 2025 ( Subtotal = $46,138 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Child Health and Human Development Extramural Research	000	1	3/20/2025	NEW	$45,574
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Child Health and Human Development Extramural Research	001	1	8/12/2025	NEW	$564
														Subtotal = $46,138

Grand Total All Awards = $93,230

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Investigating the role of FGF21 in bone homeostasis in Duchenne Muscular Dystrophy

Award Number: F30HD118663

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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