This application proposes a graduate educational program at Baylor College of Dentistry (BCD), Texas A&M University System for Mr. Joseph T. Rawlins.This program will combine PhD studies in Biomedical Sciences with concurrent clinical training leading to a DDS. Mr. Rawlins' ultimate goal is a career in dental research and academic dentistry. His research interests are directed toward growth factor regulation of bone growth in intramembranous sutures and the premature closure of sutures (craniosynostosis). A research proposal modified by Mr. Rawlins during the initial portion of his research training is submitted. This research will address hypotheses that transforming growth factor a2 (TGF-a2) regulates cell proliferation and apoptosis within the suture and these chances are associated with suture obliteration. Specifically, the research will determine: 1) if TGF-beta2 increases cell proliferation, decreases apoptosis and Twist expression in cells that express Fgfr 2, 2) whether this is followed by decreased Fgfr2 expression and increased Fgfr1 and Runx2 expression, and 3) if TGF-beta2 can induce suture obliteration in TGF-beta2 null mice calvaria in vitro, and to determine which factors are downstream of TGF-beta2 can induce suture obiliteration in TGF- beta2 null mice calvaria in in vitro, and to determine which factors are downstream of TGF-beta2 signaling by gene arrays. Experiments will use an established calvarial system to expose suture to growth factors. These experiments will provide important new information on how growth factors interact with one another to regulate cell proliferation, differentiation, and apoptosis to maintain sutures as intramembranous bone growth sites.
