Craniofacial Anomalies and Regeneration

National Institute Of Dental & Craniofacial Research

Investigators

Linked publications & trials

Abstract

Goal 1) examine and characterize both common and rare craniofacial anomalies through technologies including 3D imaging, musculoskeletal function assays, and genomic analysis to allow us to diagnosis, predict, and treat these conditions. We have been characterizing patient cohorts with craniofacial and oral dysmorphology. Two specific conditions/diseases include Loeys-Dietz syndrome and dentofacial deformities, and more recently patients with osteogenesis imperfects. We have a Natural History Craniofacial Anomalies protocol to allow for conducting comprehensive assessments and analyses to correlate phenotype and genotype. Through these protocols, we are examining and comparing the craniofacial dysmorphologies across genetic mutations to understand the perturbations in development of the face and teeth, and the influences that result in dysmorphologies. We are developing a craniofacial database that includes 3D imaging modalities. Using a TGFbeta receptor 2 KI mouse model, we have identified potential downstream effects that result in tooth and craniofacial developmental anomalies that have also been identified in patients. We have initiated a new clinical trial in OI dental anomalies management with a multi-center OI consortium. Goal 2) study bone regeneration to determine the mechanisms that distinguish bone regeneration in various environments. We have approved small animal protocols that will allow further examination of bone marrow stromal/stem cell function in the various aging environments. We have a second small animal protocol that examines a preclinical model of spontaneous bone regeneration and the influence of the aging environment. In each of these preclinical models, we are examining temporal and age-related RNA sequence variations to determine the the role of the microniche and its impact on the osteoprogenitors/BMSCs. Goal 3) morphometrics analysis of the craniofacial complex. Using 3D cone-beam CT technology and geometric morphometrics analysis methods (including PCA, PLS, CVA), we are examining the modularity and integration of the different craniofacial units to determine their integrative development. We are using this methodology to test the hypothesis of the influence of the cranial base on facial and mandibular development. Our goal is to determine if craniofacial growth and development can be predicted, thereby allowing early intervention to avoid invasive therapies, including surgery.