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Biomineralization

Research in the Forsyth Department of Biomineralization focuses primarily on elucidating mechanisms involved in the formation, preservation, destruction and repair of mineralized tissues. This work is being carried out using multi-faceted and multidisciplinary approaches, utilizing of our expertise in physical chemistry, cell and molecular biology and tissue morphology.

The Department's collective goal is to identify key cellular and molecular factors that control the formation of dental enamel. This information will be used to develop new strategies for repairing and regenerating human tooth structures. As part of this effort, novel biomimetic approaches to tissue repair currently are being developed and tested for their ability to remineralize carious tooth enamel and restore enamel structure and properties.

For example, in vitro techniques are used to determine the structure of higher-order assemblies of enamel-matrix proteins, the mechanisms by which such assemblies are formed, and the ways that they influence mineralization and crystal organization within the enamel. Studies are being advanced to characterize protein–mineral interactions and the roles of specific enamel matrix proteins in controlling mineralization. Other studies are clarifying the role of cytoskeletal elements, transmembrane molecules and the surface molecules of ameloblasts (cells that secrete enamel proteins) in controlling the organization of enamel's extracellular matrix, which in turn regulates the formation of the highly organized tooth structure. The role of these molecules in regulating cell differentiation is also under investigation. These studies, carried out by Department members, are further supported by several key outside collaborators (from the Max Planck Institute, the University of Michigan, the University of Pittsburgh, Rockefeller University, and Vanderbilt University) who bring additional expertise to Forsyth's research efforts.

Many experimental methods (SEM, TEM, confocal and atomic force microscopy, FTIR, FTIR-microscopy, dynamic light scattering, turbidity measurements, cryo-microscopy, small angle x-ray scattering, laser capture micro-dissection, microhardness determination, microradiography and others) are used to assess the structure, composition and properties of mineralized tissues and to explore the functional roles of specific extracellular matrix and tissue components.

DNA–DNA hybridization and immunohistochemistry are also used to identify bacteria associated with the destruction of hard and soft oral tissues in endodontic lesions. These activities are enhanced and stimulated by collaborations with investigators from other Forsyth departments and from other institutions (Harvard University, Boston University). Furthermore, studies are underway to clarify the interactions between tumor cells and normal surrounding cells during bone metastasis, a common complication of breast, prostate and lung cancer, that is associated with substantial bone destruction. A particular focus is the role of osteopontin, a bone protein, in tumor development and associated bone destruction.

PRINCIPAL INVESTIGATORS

Henry C. Margolis, Ph.D., Department Head
Susan Rittling, Ph.D.
Ziedonis Skobe, Ph.D.

POST-DOCTORAL FELLOWS

Felicitas Bidlack, Ph.D.
Satheesh Elangovan, BDS, D.Sc.
Kader Yagiz, Ph.D.
Shi Liang Ma, Ph.D.

The Forsyth Institute 140 The Fenway, Boston MA, 02115
V: 617.262.5200 F: 617.262.4021

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