Keith Alvares Feinberg School of Medicine, Feinberg Basic, Cell and Molecular Biology

Keith Alvares

Research Interest Keywords

Biochemistry: Proteins, Cell Biology, Extracellular Matrix

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312/503-2628

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Research Statement: Dentin phosphophoryn (DPP), the major noncollagenous protein of tooth dentin matrix is synthesized as dentin sialophosphoprotein (DSPP) by the mesenchyme-derived odontoblasts. We have found a spatio-temporal expression during mouse embryonic development in cells of epithelial origin. At day-13 of embryonic gestation, DPP was localized to the enamel organ at the developing tooth cap stage, with heaviest immuno-histochemical staining at the oral ectoderm but was also prominent in the inner enamel epithelium. Interestingly, at the same embryonic stage, DPP was also expressed in the ureteric bud branches of the metanephric kidney and in the alveolar epithelial buds of the developing lung. No expression was seen in the mesenchymal component of either organ. Interestingly inclusion of anti-DPP antibodies in E-13 organ cultures of kidneys harvested from wild type mice, altered ureteric bud morphogenesis and caused looseness of the metanephric mesenchyme. These findings suggest that besides its role in mineralization of the dentin, DPP modulates epithelial-mesenchymal interactions in meristic tissues during embryonic development. Another focus in our laboratory has been studies directed towards understanding the mechanism of mineralization in vertebrate tissues such as bone and tooth and in sea urchin tooth in invertebrates and the role of extracellular constituents of connective tissue in this complex process. The acidic protein constituent part of extracellular matrix has been implicated in mineral deposition but the precise series of molecular reaction mechanism remains undefined. In invertebrate systems, where the mineral part is calcite or aragonite the mechanisms of molecular calcification remains even much less understood compared to vertebrates where mineral deposition is chiefly calcium hydroxyapatite. We are studying whether it is the nature of the protein or environment that determines whether we get Calcium Carbonate or Calcium Phosphate crystals

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Journals

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    Publications
  • Open details Journal of Biological Chemistry
    7
  • Open details Proceedings of the National Academy of Sciences of the United States of America
    6
  • Open details Biochemical and Biophysical Research Communications
    5
  • Open details Biochemistry
    2
  • Open details Connective Tissue Research
    2

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