? The program entitled """"""""Adhesion Molecules in Transfusion Biology"""""""" seeks to continue to conduct basic research that is relevant to major problems in Transfusion Medicine. The common theme of this program is to study adhesive interactions in the vasculature including interactions among blood cells, between normal and malignant blood cells and host endothelium or tissue, and ways these interactions affect the fate, communication and function of transfused cells. In addition to studies with human cells, all projects share a general scientific approach using genetically engineered animal models, primarily mice mutant in adhesion receptors. All projects further utilize highly sophisticated imaging techniques to visualize cellular changes and behavior in vitro and in vivo. The program is composed of four highly interactive projects. Project 1, Dr. Denisa Wagner will focus on the biology of pro-coagulant microparticle generation by P-selectin/PSGL-1 interaction from leukocytes and on the pathways emanating from platelet mitochondrial injury to the activation of ADAM17 (TACE) and platelet clearance. Project 2, Dr. John Hartwig will seek to define the mechanisms that alter the surface of refrigerated platelets and target them for removal from circulation. Project 3, Dr. Ulrich von Andrian will define how transfused dendritic cells gain access to and communicate with different subsets of bone marrow resident CDS T cells. The function of leukocyte adhesion molecules in the dissemination of multiple myeloma in the BM and the potential for transfusion-based immunotherapy will be explored. The mutant mice which are an important common resource of this program, will be housed by the Animal Care Core. Electron and multiphoton microscopy will be performed as part of the Imaging 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 transfusions as well as lead to new immunotherapies and increase efficiency in hematopoietic stem cell engraftment. ?
| Majewska-Szczepanik, Monika; Paust, Silke; von Andrian, Ulrich H et al. (2013) Natural killer cell-mediated contact sensitivity develops rapidly and depends on interferon-?, interferon-? and interleukin-12. Immunology 140:98-110 |
| Muehlschlegel, Jochen D; Perry, Tjörvi E; Liu, Kuang-Yu et al. (2012) Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury. Am J Hematol 87:161-6 |
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| Jansen, A J Gerard; Josefsson, Emma C; Rumjantseva, Viktoria et al. (2012) Desialylation accelerates platelet clearance after refrigeration and initiates GPIb? metalloproteinase-mediated cleavage in mice. Blood 119:1263-73 |
| Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll et al. (2012) The origin and function of platelet glycosyltransferases. Blood 120:626-35 |
| Stadtmann, Anika; Brinkhaus, Laura; Mueller, Helena et al. (2011) Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol 41:2074-85 |
| Fuchs, Tobias A; Bhandari, Ashish A; Wagner, Denisa D (2011) Histones induce rapid and profound thrombocytopenia in mice. Blood 118:3708-14 |
| Textor, Johannes; Peixoto, Antonio; Henrickson, Sarah E et al. (2011) Defining the quantitative limits of intravital two-photon lymphocyte tracking. Proc Natl Acad Sci U S A 108:12401-6 |
| Hoffmeister, K M (2011) The role of lectins and glycans in platelet clearance. J Thromb Haemost 9 Suppl 1:35-43 |
| Ho-Tin-Noe, B; Demers, M; Wagner, D D (2011) How platelets safeguard vascular integrity. J Thromb Haemost 9 Suppl 1:56-65 |
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