The candidate is a Pediatric Cardiologist with a research interest in mechanisms of heart development. The application is submitted with the intent to provide mentored time for the candidate to pursue formal graduate level training in developmental biology and to accomplish the proposed research. Accomplishment of these goals will set the groundwork for establishing an Independent research laboratory. This proposal focuses on CMF1, a member of a novel family of proteins involved in the regulation of call division and differentiation during development. CMF1 is unique in its restriction to developing cardiac and skeletal muscle in the developing chick embryo. Its expression precedes that of contractile proteins in the developing heart tube and in skeletal myoblasts in vitro. Importantly, disruption of CMF1 expression disrupts myogenesis. There is evidence that this protein can localize both to the nucleus and to the cytoplasm of the myocyte, and that it may be cleaved Into two functional components. The experiments proposed will determine the patterns of subcellular localization and function of CMF1 proteins. Techniques proposed include generation of antibodies to various regions of the CMF1 protein, functional analyses of putative nuclear localization sequences, identification of CMF1 associated proteins, and in vitro and in vivo disruption of CMF1 functional domains. There is evidence for other, as yet undiscovered, relatives of CMF1 In mouse and possibly humans. Novel approaches to identify CMF1 related proteins are Included in this proposal. The overall goal is to elucidate novel mechanisms that regulate myogenesis and of developmental processes in general.
| Robertson, J Brian; Zhu, Tianli; Nasreen, Shampa et al. (2008) CMF1-Rb interaction promotes myogenesis in avian skeletal myoblasts. Dev Dyn 237:1424-33 |
| Dees, Ellen; Robertson, J Brian; Zhu, Tianli et al. (2006) Specific deletion of CMF1 nuclear localization domain causes incomplete cell cycle withdrawal and impaired differentiation in avian skeletal myoblasts. Exp Cell Res 312:3000-14 |
| Dees, Ellen; Robertson, J Brian; Ashe, Mabelle et al. (2005) LEK1 protein expression in normal and dysregulated cardiomyocyte mitosis. Anat Rec A Discov Mol Cell Evol Biol 286:823-32 |
