Grants We Funded

Abstract
Craniosynostosis is premature fusion of the cranial sutures. The cause is unknown, and while it is associated with numerous syndromes, most cases are sporadic. To investigate the causes and potential treatments of craniosynostosis we possess an ideal model, a colony of New Zealand White rabbits with familial, non-syndromic coronal craniosynostosis. Elucidating the gene expression of suture tissues will help us to understand how they interact and what derangements cause premature fusion. This knowledge will aid us in designing tissue engineering strategies to treat craniosynostosis. Tools to study this were previously lacking, but we have recently utilized laser capture microdissection (LCM) to isolate small, homogenous cell populations from histology sections. Genes expressed by these samples are quantified using real time PCR (rtPCR). This will allow exact localization of gene expression and accurate quantification of it for comparison between normal and synostotic tissues. Craniosynostosis is a condition of abnormal bone formation, and we have recently utilized LCM to demonstrate differences in genetic expression between craniosynostotic and wild-type coronal suture. Here, we will investigate sagittal suture from wild-type and synostotic rabbits. Samples of dura mater, periosteum, osteogenic fronts, and suture cellular contents will be isolated by LCM. We will perform rtPCR using probes targeted for markers of osteoblast differentiation: RunX2, Collagen 1A2, Alkaline Phosphatase, Osteopontin, and Osteocalcin, determining relative expression levels using Ct calculations, and comparing the tissue samples of wild-type and synostotic rabbits to assess their degree of osteoblast maturation. Many signaling factors have been implicated for their role in synostosis, including: FGF-2, FGFR-3, BMP-4, Noggin, TGFB-2, and TGFB-3. Here we will investigate the role these play in causing synostosis in our rabbits and demonstrate if their expression is different in the synostotic rabbit sagittal suture compared to wild type and synostotic coronal sutures from our previous study. Any differences observed will offer insight into the processes causing fusion in these animals, and may suggest strategies for restoring normal function in affected patient's sutures.

Biography
Brian H. Gander received his medical degree from the University of Louisville School of Medicine after completing his Bachelors of Science degree at the University of South Carolina. His undergraduate degree was obtained in Chemistry and he graduated Magna Cum Laude as well as graduating with honors from the University of South Carolina Honors College. During his medical school education Dr. Gander published articles pertaining to Composite Tissue Allotransplantation before matriculating to the University of Pittsburgh Medical Center for his training in Plastic Surgery. Dr. Gander’s current research interests include advancing craniofacial basic science research in addition to hand and reconstructive surgery.