Grants We Funded

Abstract
Craniosynostosis, the premature fusion of one or more of the developing cranial sutures, affects up to 1 in 2100 children (Hehr and Muenke 1999). Craniosynostosis may cause both skull and facial abnormalities. With an abnormally constricted skull, there is increased risk for high pressure on the developing nervous system, which can result in problems in both brain and vision development. One genetic syndrome associated with craniosynostosis is Pfeiffer Syndrome, caused by mutations in the FGFR1 or FGFR2 gene (Chokdeemboon 2013).
Current treatment of craniosynostosis consists exclusively of surgical remodeling of the cranial vault, which comes with significant risks. Additionally, in cases associated with genetic syndromes, multiple surgeries are required over the childhood of the patient for relapse of the cranial correction or to address associated facial abnormalities (Forrest 2013). The development of nonsurgical treatments for craniosynostosis is an area of continued research. In order to effectively study the biological processes behind craniosynostosis, animal models are essential. Rodent models of craniosynostosis are limited by long gestational and developmental cycles, low
reproductive capacity, and high costs. Furthermore, viral vectors are required for the creation of transgenic animals, resulting in additional variables in the process of genome editing.
Our laboratory has already described normal cranial suture development in zebrafish, as well as developed a zebrafish model of craniosynostosis based on local fibroblast growth factor function. Recently, a stable transgenic zebrafish line was created by missense mutation of fgfr1 as a model of Pfeiffer syndrome. In this study, we aim to establish a correlation between the genotype of fgfr1-mutant zebrafish line and the phenotype of cranial suture development. We will analyze the cranial development of this model throughout growth, from embryo to adult. Additionally, we aim to analyze the effect of fgfr1 mutation on downstream mediators of Fgfr1, thereby validating the craniosynostosis model on a molecular basis.
We hope that our research will further elucidate the cellular mechanisms behind craniosynostosis, with the long term goal of determining targets for nonsurgical therapies for this important problem. Development of these therapies has potential to decrease costs and improve patient outcomes in craniosynostosis.

Biography
Dr. Jennifer McGrath is a resident in integrated plastic surgery at the McGaw Medical Center of Northwestern University in Chicago, IL. She is originally from Lansdale, PA. She graduated summa cum laude with a degree in Biomedical Science from the School of Engineering and Applied Science at the University of Pennsylvania in Philadelphia, PA. She remained in Philadelphia where she obtained her medical degree from the Perelman School of Medicine at the University of Pennsylvania. While in medical school, she completed a year-long basic science research fellowship in craniofacial plastic surgery. She is currently spending a year in the Craniofacial Biology Laboratory at the Ann and Robert H. Lurie Children's Hospital of Chicago under the mentorship of Dr. Arun Gosain.