Research Division--Basic Science and Clinical
The mission of the research division is to carry out basic and applied research in aspects of bone biology, inflammation research, and extracellular matrix biology, related to regenerating new bone, controlling the loss of bone under a variety of conditions and bone and ridge augmentation in periodontal patients. One of our missions is to generate funds from various granting agents to support our research efforts in periodontics and bone biology. In this effort we can then support residents in their research thesis projects, and carry out basic research in understanding how the various cells of bone, integrate with extracellular matrix components and vascular system, under various physiological and pathological conditions. Also our mission is to carry out fundamental research in tissue regeneration, but then to integrate our basic knowledge into better clinical practices and ways to prevent and treat periodontal disease.
AREAS OF RESEARCH
The bone morphogenetic protein 2 or BMP2 is a potent cytokine/growth factor that can stimulate the entire cascade of bone formation and also integrates formation of blood vessels around new areas of bone formation. Using mouse models, we are studying the role of BMP2 in bone formation, vascularization, and mesenchymal stem cell commitment and differentiation. This mouse model in which BMP2 gene is removed from early osteoblasts, is beginning to tell us how vascularization and new bone formation are integrated at the mesenchymal stem cell level and later stages of differentiation of osteoblasts. In these efforts, we collaborate with members in Restorative Dentistry, in Xia-Dong Chen’s laboratory.
Another main area of research is in osteocyte biology. The osteocytes are thought to be in part the “brains” of bone. The osteocyte is buried in the bone matrix, integrates with the vascular system through a complex network of channels or canaliculi, and is the most abundant cell in bone tissue. It is becoming clear that the osteocyte responds to many hormones such as PTH and to the mechanical load environment of the bone tissue. Using mouse models and various ex vivo techniques we are beginning to understand how the osteocyte works, using a system biology approach, combined with various gene expression studies.
Periodontic residents also participate in studies and research of enamel matrix proteins. Using an in vivo calvarial assay, various angiogenesis assays, combined with proteomic research, we are finding the various components of enamel matrix protein that are involved in stimulating new bone formation and new vascular tissue. This will allow us to develop formulas of enamel matrix protein that are optimal for bone regeneration in cases of periodontal bone loss.
Dr. Cristina Villar's field of interest lies in Oropharyngeal candidiasis--the most common opportunistic fungal infection in bone marrow transplant, hematopoietic stem cell transplant, solid organ transplant and HIV-infected populations, occurring in as many as 90% of these patients. Despite significant advances in transplant and HIV anti-retroviral therapy, Candidal infections remain a major concern due to their impact on the overall quality of life of patients and associated risk for systemic spread. Dr. Villar’s laboratory investigates the mechanisms by which C. albicans escapes the classic endocytic trafficking pathway after its internalization by oral epithelial cells to survive and stimulate epithelial signaling pathways that promote host cell death. In these studies we use a human oral epithelial cell-C. albicans co-culture system to model host-pathogen interactions. The results of these studies will improve our understanding of how C. albicans survives and triggers extensive epithelial cell damage during oropharyngeal infections and will provide the basis for future studies focusing on the generation of novel drugs for the treatment of symptomatic oropharyngeal infection.
Professor Bjorn Steffenson’s laboratory investigates the biology of the extracellular matrix associated with health and disease. The central focus areas are the interactions between extracellular matrix components, the roles of these molecules in modifying cell behavior, and the contributions of their structural domains and modules to their overall functions. Our working hypothesis is that cells contacting structurally altered matrix molecules modify their behavior. Whereas such modifications may contribute in a positive way to normal homeostasis, they could also form the basis for negative events such as delayed wound healing and contribute to cancer cell invasion. Molecules of special interest are matrix metalloproteinases (MMPS), collagens, and fibronectin. Within this framework, we are addressing a number of research questions.
Chun, Yong-Hee, D.D.S., M.S., Ph.D.
Harris, Stephen E. , Ph.D.
Oates, Thomas W., D.D.S., Ph.D.
Steffensen, Bjorn, D.D.S., Ph.D.
Villar, Cristina, D.D.S.
Histology Lab - Bustamante, Sonja, H.T. (ASCP)