Abstract

The long range goal of the proposed research is to further our understanding of the development and functioning of blood cells and how these processes are affected in particular disease states. The program focuses on red cells and lymphocytes in man, mice and chickens with particular concentration on the structure and function of the cell surface plasma membrane during differentiation and its role in maturation of the mature cell. A multidisciplinary approach, using the tools of biophysics, molecular biology, cell biology and biochemistry is employed. The five participants in the program are each experts in one or more of these areas. Project 1 (D. Engel) focuses on the intrinsic and extrinsic factors which result in hematopoietic stem cell propagation versus differentiation. Project 2 (V. Patel and D. Williams) closely parallels this project focusing on the role of adhesive interactions between bone marrow and stromal cells in development of multipotential hematopoietic stem cells. Project 3 (S. Pierce) studies lymphocyte development focusing on the biogenesis on antigen-derived cell surface interaction structures. Project 4 (R. MacDonald) addresses the molecular basis of the mechanical properties of the erythrocyte membrane. Project 5 (L. Lorand) focuses on the role of covalent modification of membrane skeletal proteins in the erythrocyte during differentiation. Key to the success of the overall effort are the collaborative interactions among participants which will allow technical as well as intellectual contributions to the individual projects. The interactions among the five participants in the program create a unique environment for collaboration between the participating graduate students and postdoctoral fellows specializing in biochemistry, molecular biology and cell biology of blood cells. Such a broadly based study, including gene regulation and the regulation of the assembly and function of essential cellular structures, will certainly bear fruit with regard to a better understanding of hematopoietic diseases and defective functions of mature cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL045168-03
Application #
3098817
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1991-05-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201

  Publications

Koenig, Joyce M; Ballantyne, Christie M; Kumar, Ajith G et al. (2002) Vascular cell adhesion molecule-1 expression and hematopoietic supportive capacity of immortalized murine stromal cell lines derived from fetal liver and adult bone marrow. In Vitro Cell Dev Biol Anim 38:538-43
Swihart, A H; Mikrut, J M; Ketterson, J B et al. (2001) Atomic force microscopy of the erythrocyte membrane skeleton. J Microsc 204:212-25
Dutt, P; Hanenberg, H; Vik, T et al. (1997) A recombinant human fibronectin fragment facilitates retroviral mediated gene transfer into human hematopoietic progenitor cells. Biochem Mol Biol Int 42:909-17
Song, W; Wagle, N M; Banh, T et al. (1997) Wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocks the assembly of peptide-MHC class II complexes. Int Immunol 9:1709-22
Pantazatos, D P; MacDonald, R I (1997) Site-directed mutagenesis of either the highly conserved Trp-22 or the moderately conserved Trp-95 to a large, hydrophobic residue reduces the thermodynamic stability of a spectrin repeating unit. J Biol Chem 272:21052-9
Mc Kiernan, A E; MacDonald, R I; MacDonald, R C et al. (1997) Cytoskeletal protein binding kinetics at planar phospholipid membranes. Biophys J 73:1987-98
Xu, X; Press, B; Wagle, N M et al. (1996) B cell antigen receptor signaling links biochemical changes in the class II peptide-loading compartment to enhanced processing. Int Immunol 8:1867-76
Freie, B W; Dutt, P; Clapp, D W (1996) Correction of Fanconi anemia type C phenotypic abnormalities using a clinically suitable retroviral vector infection protocol. Cell Transplant 5:385-93
Moritz, T; Dutt, P; Xiao, X et al. (1996) Fibronectin improves transduction of reconstituting hematopoietic stem cells by retroviral vectors: evidence of direct viral binding to chymotryptic carboxy-terminal fragments. Blood 88:855-62
Orazi, A; Du, X; Yang, Z et al. (1996) Interleukin-11 prevents apoptosis and accelerates recovery of small intestinal mucosa in mice treated with combined chemotherapy and radiation. Lab Invest 75:33-42

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