I have always been interested in the genetic circuitry of tissue formation and patterning that occurs during development. Homeobox genes are DNA binding transcription factors that are intimately involved in these processes, and they are present in all species from Drosophila to human. Since I cloned the Prrx1 gene 25 years ago my research has focused on understanding its function. I have generated mouse models deficient in this gene and its homolog Prrx2 to uncover the overlapping and independent functions of the closely related paired type homeobox proteins. Null mice revealed that the Prrx1 and Prrx2 genes are critical for morphogenesis of teeth, hair, salivary glands, bone and blood vessels. Many of the regions impacted by Prrx deletions are craniofacial, which ties in with my didactic teaching of histology and embryology to dental students and residents. Throughout the years, 36 students have worked in my lab and contributed to our understanding of the role of Prrx genes in morphogenesis: 1-DMD Ph.D., 3-PhD, 1-MS, 22-DMD, 7-undergraduates, and 2-high school students.
Current and Future Research Interests
Research in my laboratory is currently focused on the carboxyl terminal region of the Prrx proteins which contains an OAR domain. In total there are 16 human proteins that contain a version of the OAR domain. Although it is phylogenetically conserved through Drosophila, not much is known about this domain in any specie. Work in our laboratory and others has led to the hypothesis that the OAR domain is a cofactor binding site, and that protein-protein interactions between the 16 OAR containing proteins and an unknown suite of cofactors likely modulate transcription of nearby genes. My current research is focused on identifying these OAR cofactors, their specificity for the 16 OAR domains, and how these interactions modulate transcriptional regulation. This work is critical since all 16 OAR containing proteins are integral to morphogenesis of many tissues and organs. In addition, our collaborative work recently published in Cell has demonstrated that Prrx1 is linked to diabetes, therefore highlighting an additional role for these important homeodomain proteins.
I have a long standing and ongoing collaborative project in the area of biomechanical engineering of the Temporal Mandibular Joint (TMJ) with Hai Yao, Ph.D. of the Clemson-MUSC Bioengineering Program. Our work together has illuminated many cell biological and mechanical properties of TMJ disc cells. This data is being collected in order to create a finite element bioengineering model of TMJ function. The ultimate goal is to be able to integrate this computer simulation model with personal TMJ function information to derive predictions on the potential of TMJ pathogenesis, to better define regeneration potential, and to guide production of patient-tailored implantable devices.