# Role of a craniosynostosis associated fibroblast growth factor receptor mutation in extraocular muscles

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $268,802

## Abstract

PROJECT SUMMARY
 Craniosynostosis syndromes are a group of devastating developmental disorders characterized by
craniofacial abnormalities and strabismus, or eye misalignment. The most common craniosynostosis syndromes,
including Apert Syndrome, are associated with genetic mutations in fibroblast growth factor receptor 2 (Fgfr2).
Strabismus in Apert syndrome patients is difficult to treat due to high surgical failure rates. Sadly, untreated
strabismus is closely correlated with amblyopia, vision loss, and significant functional and psychosocial
difficulties that negatively impact quality of life for patients.
 It is unclear how abnormal FGFR2 signaling is associated with strabismus in patients with Apert
syndrome. These patients have abnormal bony orbits and abnormal extraocular muscles (EOM) because of a
known Fgfr2 mutation; however, it is not well understood how abnormal FGFR2 signaling, abnormal bony orbits,
and abnormal EOM clinically manifest as strabismus. Previous research shows atypical EOM, specifically
smaller EOM and myofiber disorganization, in both human Apert patients and in the Apert mouse model.
 Scientific investigations will focus on identifying the contributing determinants that govern abnormal EOM
structure and function in Apert syndrome and the key factors that cause EOM disease using a mouse model for
Apert syndrome. EOM anatomy and function will be analyzed using MRI, histology, and muscle functional
studies. Mutant mice that only express the Fgfr2 mutation in muscle, muscle stem cells, bone, or innervating
neurons will be used to characterize the contributions of abnormal FGFR2 signaling in different tissues to altered
EOM structure and function in Apert syndrome. A novel gene therapy that specifically targets the abnormal Fgfr2
mutation in Apert syndrome will also be tested in our Apert mouse model using similar techniques.
 Dr. Rudell has proposed a career development plan to reach her goal of becoming an independent
clinician scientist with an expertise in EOM physiology. Her research background in synaptic development in
skeletal muscle intersects perfectly with her clinical interests in pediatric ophthalmology and EOM disease. Her
department is extremely supportive of her career goals at the University of California San Diego, with access to
outstanding mentors and research facilities. Her career development plan includes coursework and hands-on
research projects in genetics and muscle biomechanics. Her mentors are leading scientists and clinicians in
muscle physiology, craniofacial genetics, and pediatric ophthalmology, with excellent training records. They are
unequivocally committed to Dr. Rudell’s success as an independent clinician scientist.

## Key facts

- **NIH application ID:** 10846629
- **Project number:** 5K08EY034930-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jolene Rudell
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $268,802
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846629

## Citation

> US National Institutes of Health, RePORTER application 10846629, Role of a craniosynostosis associated fibroblast growth factor receptor mutation in extraocular muscles (5K08EY034930-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10846629. Licensed CC0.

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