The candidate is currently an Instructor and Fellow in Medicine in the Hematology Unit at the University of Rochester. She received her B.S. and M.D. degrees from the University of North Carolina at Chapel Hill followed by a three year residency in internal medicine and a one year clinical fellowship in hematology, both at the University of Rochester Medical Center. She has just completed her second year as a research fellow in the Hematology Unit where she has initiated studies examining interactions of endothelial cells with fibrin. The candidate's goal is to pursue further research training to develop the skills and experience required to become an independent investigator. The focus of the proposed five year career development plan is a research project based on the candidate's preliminary studies and designed to develop her research abilities.
The specific aims of the research proposal are to 1) identify and characterize sites on the fibrin molecule that mediate non-RGD dependent endothelial cell adhesion and spreading on non- crosslinked fibrin and 2) to characterize the role of factor XIIIa-mediated crosslinking on endothelial cell adhesion and spreading on crosslinked fibrin. Preliminary studies indicate that a site near the amino terminus of the fibrin beta chain is involved in mediating endothelial cell spreading. The experimental design involves quantitation of the adhesion and spreading of human umbilical vein endothelial cells on fibrin surfaces of varying structure to identify sites mediating the endothelial cell response. Specific fibrin fragments and peptides derived particularly from the amino terminus of the fibrin beta chain will be used in inhibition and direct attachment studies to localize the amino acid sequence that mediates adhesion and spreading. Monoclonal antibodies reactive with epitopes at the amino terminus of the fibrin beta chain will also be examined for inhibitory activity. Thrombin-inducible, non-RGD mediated endothelial cell adhesion will be examined using non-crosslinked fibrin lacking the carboxyl terminal Aalpha chain RGD site, testing inhibition of adhesion to this substrate using peptides, fragments and antibodies. The role of factor XIIIa crosslinking on the endothelial cell-fibrin interaction will be evaluated by examining endothelial cell adhesion and spreading on fibrin substrates varying in the extent of alpha and gamma chain crosslinking. The University of Rochester Medical Center and the Hematology Unit provide an environment that is supportive of research and the development of the candidate's academic career. Guidance in the research project and in career development will be provided by the Sponsor, Co-Sponsor and Advisory Committee. Academic enrichment will also include courses in cell biology and biostatistics, research seminars and interaction with M.D. and Ph.D. research scientists in the Hematology Unit with expertise in fibrin(ogen) structure, endothelial cell biology, molecular biology, protein chemistry and cell matrix interactions.
| Odrljin, T M; Francis, C W; Sporn, L A et al. (1996) Heparin-binding domain of fibrin mediates its binding to endothelial cells. Arterioscler Thromb Vasc Biol 16:1544-51 |
| Sporn, L A; Bunce, L A; Francis, C W (1995) Cell proliferation on fibrin: modulation by fibrinopeptide cleavage. Blood 86:1802-10 |
| Hamaguchi, M; Bunce, L A; Sporn, L A et al. (1994) Plasmic degradation of fibrin rapidly decreases platelet adhesion and spreading. Blood 84:1143-50 |
