Cynthia Peterson, Ph.D.

Research Statement

Ongoing research focuses on the areas of blood coagulation & fibrinolysis and cell-matrix interactions using a combination of protein biochemistry, molecular biology and cell biology. Defenses against injury and disease such as formation and lysis of blood clots and aspects of cellular immunity are achieved by interactions of circulating biomolecules with cell surfaces and vessel walls. Most of the activities are dedicated to understanding the structure and function of vitronectin, an abundant protein in the blood that regulates many physiological processes. Circulating vitronectin associates with tissue matrices, and its presence is important in pathological situations or in cancer metastasis and tissue remodeling. The factors that control the binding interactions and determine activities of vitronectin in the circulation as well as in the matrix are important unsolved issues. Complexes of vitronectin with biological targets (other proteins in the circulation and on cell surfaces) regulate the dynamic processes of coagulation vs. fibrinolysis and binding vs. release from the matrix. Approaches that encompass a wide spectrum of biophysical and cellular and molecular biological techniques are used to approach important questions regarding the specificity of interaction of vitronectin with many of its biological targets. Methods include eukaryotic cell culture/transfection; eukaryotic and prokaryotic expression systems; site-directed mutagenesis; protein purification; analytical ultracentrifugation; fluorescence spectroscopy; and calorimetry.

Selected Publications

Balbo A, Minor KH, Velikovsky CA, Mariuzza RA, Peterson CB and Schuck P (2004) Studying Multi-Protein Complexes by Multi-Signal Sedimentation Velocity Analytical Ultracentrifugation. Proc. Natl. Acad. Sci. USA, in press.

Lynn GW, Heller WT, Mayasundari A, Minor KH and Peterson CB (2004) A Model for the Three-Dimensional Structure of Human Plasma Vitronectin from Small Angle Scattering Measurements.”Biochemistry, in press.

Horn NA, Hurst GB, Mayasundari A, Whittemore NA, Serpersu EH and Peterson CB (2004) Assignment of the Four Disulfides in the N-terminal Somatomedin B Domain of Native Vitronectin Isolated from Human Plasma. J. Biol. Chem. 279: 35867-35878.

Mayasundari A, Whittemore NA, Serpersu EH and Peterson CB (2004) The Solution Structure of the N-terminal Domain of Human Plasma Vitronectin: Location of Binding Sites that Regulate Fibrinolysis and Cell Migration. J. Biol. Chem. 279: 29359-29366.

Minor KH and Peterson CB (2002) PAI-1 Promotes the Self-Association of Vitronectin into Complexes Exhibiting Altered Incorporation into the Extracellular Matrix. J. Biol. Chem. 277: 10337-10345.

Podor TJ. Campbell S, Chindemi P, Foulon DM, Farrell DH, Walton PD, Weitz JI and Peterson CB (2002) Incorporation of Vitronectin into Fibrin Clots: Evidence for a Binding Interaction between Vitronectin and gA/g' Fibrinogen. J. Biol. Chem. 277: 7520-7528.

Xu D, Baburaj K, Peterson CB and Xu Y (2001) A Model for the Three-Dimensional Structure of Vitronectin: Predictions for the Multi-Domain Protein from Threading and Docking. Proteins: Structure, Function and Genetics 44: 312-320.

Gibson AD and Peterson CB (2001) Full Length and Truncated Forms of Vitronectin Provide Insight into Effects of Proteolytic Processing on Function. Biochim. Biophys. Acta 1545: 389-403.

Podor TJ, Shaughnessy SG, Blackburn MN and Peterson CB (2000) New Insights into the Size and Stoichiometry of the Vitronectin:PAI-1 Complex. J. Biol. Chem. 275: 25402-25410.

Podor TJ, Peterson CB, Lawrence DA, Stefansson S, Shaughnessy SG, Foulon DM, Butcher M and Weitz, J. I. (2000) Plasminogen Activator Inhibitor Binds to Fibrin via Vitronectin. J. Biol. Chem. 275: 19788-19794.

Gibson AD, Lamerdin JA, Zhuang P, Baburaj K, Serpersu EH and Peterson CB (1999) Orientation of Heparin-Binding Sites in Native Vitronectin: Analyses of Ligand Binding to the Primary Glycosaminoglycan-binding Site Indicate that Putative Secondary Sites are Not Functional. J. Biol. Chem. 274: 6432-6442.

Contact Information

Office:
Room F-331A
Walters Life Sciences
Phone: (865) 974-4083

Lab:
Room E-302
Walters Life Sciences
Phone: (865) 974-4093

Email: cbpeters@utk.edu