This proposal sets forth a plan to elucidate the role o FGF receptors in de terming cellular responsiveness to FGF, and describes a strategy that will guide the I to become an independent investigator.. The PI has spent the last 10 years preparing for a career in academic medicine. His Ph.D. provided a foundation in basic science research while his m.D. broadened interests and knowledge of human disease and therapy. Residency training has defined his professional role as an Academic Pathologist with a focus on basic cardiovascular research. The candidate desires an understanding of molecular approaches to clinically relevant problems in order to apply more diverse strategies towards understanding cardiovascular disease. The research focus of the training program will be in the regulation of myogenic development by fibroblast growth factors. Specifically, the candidate will determine the role of receptor-mediated FGF signaling in regulating myogenic differentiation. This goal will be accomplished by genetically manipulating FGF receptor availability and then assessing the effects on skeletal myoblast proliferation and differentiation. In addition, the candidate will investigate the role of the secreted form of the FGF receptor in regulating myogenesis. The results will be of general importance for the understanding of growth factor regulation of the complex processes of myogenic development. The results obtained in skeletal myocytes may be directly extendable to cardiac myocytes and to smooth muscle cells. By understanding the determinants of myoblast proliferation and differentiation, it may be possible to develop strategies to intervene in disease processes such as coronary restenosis following angioplasty and myocyte loss following infarction. In addition, defining the biologic effects of the secreted form of the FGF receptor may provide an important and powerful tool for modulating the in vivo effects of FGF.
| Scata, K A; Bernard, D W; Fox, J et al. (1999) FGF receptor availability regulates skeletal myogenesis. Exp Cell Res 250:10-21 |
