Research
Our research is centered on understanding and treating the processes underlying craniofacial and dental malformations, which are among the most common congenital abnormalities and have profound impacts on the lives of patients and their families. Our main focus is the use of mice as a genetic model system to elucidate the mechanisms responsible for normal and perturbed development of teeth, facial skeleton, taste papillae, and other organs. Specifically, we are interested in the role of growth factor signaling and cell-matrix interactions in the formation of orofacial structures and in the regulation of adult stem cells in teeth.
Currently, there are two principal projects in the lab. The first is the analysis of adult stem cells in the mouse incisor. It is known that the maintenance, repair and growth of many adult organs, such as the bone marrow, skin, hair, brain, and gastrointestinal tract, depend on tissue-specific populations of stem cells. Similarly, the mouse incisor requires the presence of adult stem cells because, unlike human teeth, it grows continuously throughout the life of the animal. We are working to understand the molecular processes that regulate the behavior of dental stem cells, including their capacity to self-renew as well as to differentiate into the various cellular components of the tooth, such as the enamel-producing ameloblasts and dentin-producing odontoblasts. We intend to use the insights provided by our experiments in mice to guide us in the use of stem cells in regenerating dental tissues.
Our second main project involves the study of the mechanisms responsible for embryonic tooth development. This process, like the development of many organs, is driven by the dialogue between two tissues, the epithelium and the mesenchyme. Epithelial-mesenchymal communication occurs via soluble molecules that are members of the FGF, BMP, HH and WNT families of signaling molecules. We have shown that inactivating mutations in antagonists of FGF signaling, known as Sprouty genes, result in the presence of supernumerary teeth. Ongoing efforts in this area of investigation include genetic and biochemical approaches to the role of FGF and HH genes in tooth morphogenesis. We are also studying the roles of these signaling molecules in the patterning and outgrowth of other craniofacial structures, including taste papillae and the facial skeleton.
In addition to our experiments in mice, we are collecting cohorts of patients with craniofacial and dental birth defects. To identify new genes involved in these processes, we are using array comparative genomic hybridization, linkage analysis and candidate gene sequencing. We intend to integrate the human and mouse studies by using mouse genetic approaches to understand how mutations in the human genes we identify cause anomalies.