The proposed career development plan has two components: biomedical research, additional training in advanced experimental techniques. The research project will test the hypothesis that alterations in the expression of active MMPs are crucial early indicators of the conversion of endothelial cells from the quiescent to the angiogenic or angiotumorigenic phenotypes. In vitro experiments with unique tumorigenic and nontumorigenic lymphatic, venous, and microvascular endothelial cells will be extended to an in vivo model. The synergistic influence of VEGF165 and bFGF, (cytokines which induce angiogenesis) and of inhibitors of MMP activity (TIMPs, antibodies and tetracycline) upon MMP expression will be evaluated in vitro and in vivo. Brief visits to other laboratories will provide opportunities to train, consult, and share expertise with colleagues and advisory committee members, to enhance the candidate's ability to translate results of basic research into clinical applications.
