The program entitled """"""""ADHESION MOLECULES IN TRANSFUSION BIOLOGY"""""""" seeks to conduct basic research that is relevant to major problems of Transfusion Medicine. The common theme of this program is the investigation of adhesive interactions among blood cells and host endothelium; and ways in which they affect the fate and function of transfused cells. The interaction of adhesion receptors with cytoskeletal and signaling elements and the importance of shape change directed by these elements for blood cell function will also be addressed. In addition to studies with human cells, all projects will share a general scientific approach using genetically engineering animal models deficient in adhesion receptors or cytoskeletal components. The program is composed of four highly interactive projects. In project 1, Drs. Wagner, Groopman and Avraham will examine the adhesive interactions of megakaryocytes and platelets with other vascular cells during platelet generation, storage, circulation and clearance. The development of the platelet storage lesion will be closely scrutinized. In project 2, Drs. Hartwig and Kwiatkowski will study the mechanisms involved in sphering of cooled platelets and how this affects adhesive functions of the platelets. New inhibitors of platelet shape change in the cold will also be tested. In project 3, Drs. von Andrian and Gutierrez-Ramos will identify the adhesion receptors responsible for homing of leukocytes to peripheral lymph nodes and of hematopoietic stem cells to bone marrow. Hematopoietic stem cell mobilization to peripheral blood will also be studied. In project 4, Drs. Remold-O'Donnell and Ardman will investigate a molecule that modulates adhesion and often manifests anti-adhesive properties. The role this molecule plays in regulation of adhesiveness of circulating blood cells and in the maintenance of functional integrity of blood cell products will be evaluated. The null mice, which are an important common resource of this program, will be housed by the Animal Care Core. We hope that the proposed basic research in cell adhesion will lead to better preservation of blood products, reduce adverse side effects, and improve the outcome of transfusion, as well as increase the efficiency in hematopoietic stem cell engraftment.
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