The objective will be to investigate the role of specific macromolecules involved in the cellular recoginition (cell-cell) and in the recognition of the extracellular matrix components (cell-ECM) in cardiac morphogenesis. Investigations will be conducted to: 1) isolate and characterize cell surface macromolecules involved in cell-cell and cell-ECM recongintion; 2) develop both polyclonal and monoclonal antibodies to these isolated macromolecules; 3) conduct bioassays to determine the role of these macromolecules at specific times of development of the heart; 4) analyse the association between these cell surface components and the cytoskeleton of developing myocytes; and 5) examine the expression of these components at specific periods of morphogenesis using cDNA technology and image enhancement analysis. Fundemental to the formation of the heart are the specific cell-cell and cell-ECM interactions at all stages of development from the embryo to the adult. These complex interactions between the three principal cell types of the heart (myocytes, fibroblasts and endothelial cells) will be examined. Initially, cell adhesion assays will be conducted with fetal, neonate and adult myocytes, fibroblasts and endothelial cells to determine the similarities and differences in the recognition of the cell types for purifies ECM components such as fibronectin, laminin and various types of collagens. Cell-cell adhesion will also be assayed with these same cell types. Using an immunological approach, antibodies will be prepared against purified extracts to the cell surface and used for: 1) inhibition of cell-cell and/or cell-ECM interactions, and 2) purification and identification of the specific macromolecule(s). Antibodies produced against cell surface components will be examined at different times of development using recombinant cDNA technology and by fluorescent microscopy. The role of cell sorting in the formation of of the heart will be examined after the development of specific cell surface probes of the 3 principal cell types. The specific interaction of these cell surface components with cytoskeleton in relation to cardiac morphogenesis will be investigated using antibodies against the cell surface markers and various components of the cytoskeleton. Through these investigations on the role of cell-cell and cell-ECM receptors we will attempt to further elucidate the complex biochemical controls of cardiac morphogenesis.
| Morales, Mary O; Price, Robert L; Goldsmith, Edie C (2005) Expression of Discoidin Domain Receptor 2 (DDR2) in the developing heart. Microsc Microanal 11:260-7 |
| Borg, Thomas K (2004) It's the matrix! ECM, proteases, and cancer. Am J Pathol 164:1141-2 |
| Goldsmith, Edie C; Carver, Wayne; McFadden, Alex et al. (2003) Integrin shedding as a mechanism of cellular adaptation during cardiac growth. Am J Physiol Heart Circ Physiol 284:H2227-34 |
| Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K (2002) Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy. Circ Res 91:888-98 |
| Goldsmith, Edie C; Borg, Thomas K (2002) The dynamic interaction of the extracellular matrix in cardiac remodeling. J Card Fail 8:S314-8 |
| Knezevic, V; Sim, A J; Borg, T K et al. (2002) Isotonic biaxial loading of fibroblast-populated collagen gels: a versatile, low-cost system for the study of mechanobiology. Biomech Model Mechanobiol 1:59-67 |
| Ross, R S; Borg, T K (2001) Integrins and the myocardium. Circ Res 88:1112-9 |
| Ding, B; Price, R L; Goldsmith, E C et al. (2000) Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure. Circulation 101:2854-62 |
| Yost, M J; Simpson, D; Wrona, K et al. (2000) Design and construction of a uniaxial cell stretcher. Am J Physiol Heart Circ Physiol 279:H3124-30 |
| Kanekar, S; Borg, T K; Terracio, L et al. (2000) Modulation of heart fibroblast migration and collagen gel contraction by IGF-I. Cell Adhes Commun 7:513-23 |
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