Abstract

The purpose of this grant proposal is to investigate role of thrombospondin (TSP) in hemostasis and cell adhesion. We will test the hypothesis that TSP polymers support cell adhesion whereas monomers bind fibrinogen and function to support platelet aggregation. The proposal will investigate the factors that effect TSP monomer-polymer conversions as well as biochemically characterize the different subunit forms of TSP. Additionally, we will characterize the platelet-TSP receptors by means of TSP- platelet binding studies, TSP-photoaffinity labeling studies, TSP affinity chromatography, and anti-TSP affinity chromatography, and anti-TSP monoclonal antibody production. We will investigate the role of TSP in clot formation and cell adhesion. Our ultimate goal is to discover by the use of monoclonal antibodies which molecular interactions of TSP play an important role in blood coagulation and cell adhesion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028149-07
Application #
3339555
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1988-06-01
Project End
1992-03-31
Budget Start
1989-04-15
Budget End
1990-03-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129

  Publications

Nicosia, R F; Tuszynski, G P (1994) Matrix-bound thrombospondin promotes angiogenesis in vitro. J Cell Biol 124:183-93
Hosokawa, T; Sigel, B; Machi, J et al. (1994) Experimental assessment of spectrum analysis of ultrasonic echoes as a method for estimating scatterer properties. Ultrasound Med Biol 20:463-70
Tuszynski, G P; Nicosia, R F (1994) Localization of thrombospondin and its cysteine-serine-valine-threonine-cysteine-glycine-specific receptor in human breast carcinoma. Lab Invest 70:228-33
Muraishi, A; Capuzzi, D M; Tuszynski, G P (1993) Binding of thrombospondin to human plasma lipoproteins. Biochem Biophys Res Commun 193:1145-51
Tuszynski, G P; Rothman, V L; Papale, M et al. (1993) Identification and characterization of a tumor cell receptor for CSVTCG, a thrombospondin adhesive domain. J Cell Biol 120:513-21
Hosokawa, T; Muraishi, A; Rothman, V L et al. (1993) The effect of thrombospondin on invasion of fibrin gels by human A549 lung carcinoma. Oncol Res 5:183-9
Kowalska, M A; Tuszynski, G P (1993) Interaction of thrombospondin with platelet glycoproteins GPIa-IIa and GPIIb-IIIa. Biochem J 295 ( Pt 3):725-30
Tuszynski, G P; Rothman, V L; Deutch, A H et al. (1992) Biological activities of peptides and peptide analogues derived from common sequences present in thrombospondin, properdin, and malarial proteins. J Cell Biol 116:209-17
Tuszynski, G P; Smith, M; Rothman, V L et al. (1992) Thrombospondin levels in patients with malignancy. Thromb Haemost 67:607-11
Tuszynski, G P; Kowalska, M A (1991) Thrombospondin-induced adhesion of human platelets. J Clin Invest 87:1387-94

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