The theme of this SCOR renewal application is to investigate the function of specific proteins carrying blood group antigens and their impact on health and disease. The objectives are: a) Link specific blood group genotypes with disease processes and develop understanding of the molecular basis for the disease; b) Determine structure/function relationships of clinically significant blood groups; and c) introduce to the blood banking community more precise and convenient methods for typing RBC antigens and for identifying antibodies. To accomplish more precise and convenient methods for typing RBC antigens and for identifying antibodies. To accomplish these goals we have a collaborative group composed of four projects and three core units: Project 1 aims to elucidate the functions of the Rh family of proteins, and requirements for expression of Rh antigens on the RBC surface. This is important in understanding clinical aspects of blood transfusion, autoimmune hemolytic anemia, and hemolytic disease of the newborn. Project 2 plans to define the functions of the Kell/XK complex. Kell participates in the activation of endothelins, which are involved in the regulation of vascular tone and lack of XK is associated with the McLeod syndrome. This project will also determine the mechanisms by which antibodies to associated with the McLeod syndrome. This project will also determine the mechanisms by which antibodies to Kell antigens suppress erythropoiesis and induce fetal anemia. Project 3 will identify the RBC receptors and the parasite ligands that are essential for plasmodium vivax and P. falciparum invasion and their specific interactions. This could lead to development of new prophylactic agents such as drugs or vaccines to prevent malaria. Project 4 will express protein carrying blood group antigens at levels equivalent to that on RBCs so as to develop an automated and objective method to detect and identify clinically- significant blood group antibodies. This project will also study diversity of blood group genes in different populations and to engineer clinically relevant monoclonal antibodies. Administrative, Cell Sorting, and Antibody Production core units support the projects. Overall the program provides an integrated approach for studying the molecular and cell biology of blood groups and applying the knowledge gained to modernize blood banking procedures and for developing detailed understanding of the functions of blood group antigens and their possible relations to human disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL054459-07
Application #
6490561
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (S1))
Program Officer
Mondoro, Traci
Project Start
1996-02-01
Project End
2005-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
7
Fiscal Year
2002
Total Cost
$1,384,493
Indirect Cost
Name
New York Blood Center
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
Migliaccio, Anna Rita (2018) A vicious interplay between genetic and environmental insults in the etiology of blood cancers. Exp Hematol 59:9-13
Ciaffoni, Fiorella; Cassella, Elena; Varricchio, Lilian et al. (2015) Activation of non-canonical TGF-?1 signaling indicates an autoimmune mechanism for bone marrow fibrosis in primary myelofibrosis. Blood Cells Mol Dis 54:234-41
Hricik, Todd; Federici, Giulia; Zeuner, Ann et al. (2013) Transcriptomic and phospho-proteomic analyzes of erythroblasts expanded in vitro from normal donors and from patients with polycythemia vera. Am J Hematol 88:723-9
Poletto, Valentina; Rosti, Vittorio; Villani, Laura et al. (2012) A3669G polymorphism of glucocorticoid receptor is a susceptibility allele for primary myelofibrosis and contributes to phenotypic diversity and blast transformation. Blood 120:3112-7
Huang, Cheng-Han; Ye, Mao (2010) The Rh protein family: gene evolution, membrane biology, and disease association. Cell Mol Life Sci 67:1203-18
Zhu, Xiang; Rivera, Alicia; Golub, Mari S et al. (2009) Changes in red cell ion transport, reduced intratumoral neovascularization, and some mild motor function abnormalities accompany targeted disruption of the Mouse Kell gene (Kel). Am J Hematol 84:492-8
Mutschler, Manuel; Magin, Angela S; Buerge, Martina et al. (2009) NF-E2 overexpression delays erythroid maturation and increases erythrocyte production. Br J Haematol 146:203-17
Ford, Louise; Lobo, Cheryl A; Rodriguez, Marilis et al. (2007) Differential antibody responses to Plasmodium falciparum invasion ligand proteins in individuals living in malaria-endemic areas in Brazil and Cameroon. Am J Trop Med Hyg 77:977-83
Peng, Jianbin; Redman, Colvin M; Wu, Xu et al. (2007) Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases. Gene 392:142-50
Hue-Roye, Kim; Lomas-Francis, Christine; Belaygorod, Larisa et al. (2007) Three new high-prevalence antigens in the Cromer blood group system. Transfusion 47:1621-9

Showing the most recent 10 out of 143 publications