This application describes a collaborative research program directed toward a better understanding of the physiology and genetic control of blood components and of their safe and effective use in transfusion therapy. This will be achieved through collaborative, interactive research projects that bring together scientists who utilize a wide range of key technologies. The research will seek a better understanding of the structure and function of the alpha-2 macroglobulin receptor (Project 1), the molecular interactions of fibronectin with collagen, heparin, and the fibronectin receptor (Project 2), the structural basis by which intracellular iron controls the synthesis of ferritin and transferrin receptor (Project 3), the control and potential use of organ-like neovascular structures induced by heparin binding growth factor-1 as a potential means of introducing new genetic information (Project 4), the role of the hepatitis B virus in inducing hepatocellular carcinoma in transgenic mice (Project 5), and the production and characterization of factor VIII fragments in order to assess their potential for therapy of factor VIII inhibitor antibodies (Project 6). These projects emphasize the interaction of plasma proteins with cellular receptors, the use of transgenic mice to better characterize the molecular basis of angiogenesis and viral disease pathogenesis, and the use of domains and fragments of plasma proteins in order to better understand their function and to consider their therapeutic applications. These projects will be directed by a group of senior scientists at the Jerome H. Holland Laboratory, a new research facility that has been established by the American Red Cross to provide research and development support for its Blood Service programs. The six research projects will be supported by central, core facilities that prepare monoclonal and polyclonal antibodies (Core B), synthesize peptides and oligonucleotides and carry out protein amino acid and microsequence analysis (Core C), and provide administrative support for the SCOR program (Core A). This SCOR application is based on the contention that the interface of new technologies and interrelated projects will enhance the scientific productivity of these established, independent laboratories.
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