Marc D McKee
Mineralized tissues and extracellular matrix biology, pathologic calcification, bone and tooth cell biology, osteopontin, matrix Gla protein.
Research in my laboratory is primarily focused on mineralization (calcification) in extracellular matrices of bones and teeth, in mineralization pathologies, and in other biomineralizing systems such as inner-ear otoconia and eggshells. In particular, we are investigating the role of mineral-binding proteins, peptides, amino acids and other small molecules in crystal growth during normal hard-tissue mineralization, and in rare hypomineralization (osteomalacia) diseases of bones and teeth such as X-linked hypophosphatemia and hypophosphatasia. We also investigate how enzymes modify these factors to influence their mineralization-regulating activities. Our work also includes investigating pathologic circumstances and the actions of regulatory molecules where unwanted and debilitating mineral is deposited in soft tissues such as in the kidney (urolithiasis, kidney stones) and in blood vessels (vascular calcification). The proteins/enzymes that we are currently focusing on are osteopontin and PHEX. We also examine extracellular matrix organization and composition at cell- and matrix-matrix interfaces, and we examine the nanostructure of mineralized tissues. To study these processes, a variety of morphological, biochemical, immunochemical, cell biological and molecular techniques are used which include among others: electron microscopy and tomography, focused-ion beam milling, atomic force microscopy, confocal microscopy, immunocytochemistry, in vivo experimentation using normal and transgenic mice, in vitro cell culture and crystal growth systems, and standard biochemical and chemical assays.
Keywords: Extracellular matrix, biomineralization, bone, teeth, osteopontin, electron microscopy, PHEX, osteomalacia, X-linked hypophosphatemia, hypophosphatasia