Skeletal dysplasias constitute an important group of congenital birth defects. Children with these disorders may die in infancy, and survivors may have malformations and disabilities that significantly impact their quantity and quality of life. Craniosynostosis and chondrodysplasias are skeletal dysplasias caused by activating mutations in fibroblast growth factor receptors (Fgfrs), highlighting the critical role of FGF signaling in both membranous and endochondral bone development. The candidate has generated mice lacking both Fgf9 and Fgf18 that show severe skeletal abnormalities, including striking agenesis of the calvarial bones, enabling her to characterize membranous bone development in early embryogenesis. This application will explore the mechanisms by which FGF9 and FGF18 regulate membranous bone formation, using murine calvarial development as a model system. The results of these proposed studies will enhance our understanding of FGF signaling in skeletal biology, and may promote the development of treatment strategies for patients with skeletal dysplasias. The candidate's long-term objective is to understand the genetic pathways that regulate skeletal biology. She hypothesizes that FGF9 and FGF18 are critical FGF ligands that regulate membranous bone development. Thus the following specific aims are proposed: 1. Determine the cellular mechanism(s) by which FGF9 and FGF18 signaling regulate(s) calvarial development and membranous bone formation, and 2. Define molecular signaling networks in calvarial development and membranous bone formation. A well structured career development plan, extensively supported with institutional resources and internationally known mentors, has been designed to allow the candidate to transition during the tenure of the K award to an independent tenure-track faculty investigator. Thus, she will receive the necessary training both to direct an active research program and to provide state-of-the-art clinical care.

Public Health Relevance

Skeletal dysplasias constitute an important group of congenital birth defects that can profoundly impact quantity and quality of life for children. The data generated from these proposed studies will enhance our understanding of molecular mechanisms in skeletal biology and may promote the development of treatment strategies for patients with skeletal dysplasias and other bone disorders.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD058219-04
Application #
8476241
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Javois, Lorette Claire
Project Start
2010-07-15
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$137,160
Indirect Cost
$10,160
Name
University of Utah
Department
Pediatrics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112