|
Faculty
Velia Fowler
Professor
Department of Cell Biology
TSRI - 1987
Education
B.A., Oberlin College, 1974
Ph.D., Harvard University, 1980
Awards & Activities
Vice-Chair, Gordon Research Conference on Red Cells, Tilton, NH, 2009; Chair in 2011
Chair, Gordon Research Conference on "Motile and Contractile Systems", Colby-Sawyer College, NH, 2003
Chair, Cell and Developmental Function F05 Fellowship Review Group ZRG F05, National Institutes of Health, 2001-2003
Research Focus
Actin Dynamics: Roles in Cell and Tissue Morphogenesis in Development
Our laboratory studies the role of actin dynamics in regulating assembly and function of the diverse cytoskeletal structures that contribute to cell and tissue morphogenesis during embryonic development. Current research focuses on tropomodulins (Tmods), a conserved family of actin pointed end-capping proteins that block association and dissociation at slow-growing (pointed) ends of actin filaments. Tmods also bind tropomyosins (TMs), which cooperate with Tmods to tightly cap actin pointed ends, regulating actin filament lengths and stability in the spectrin-based membrane skeleton of non-muscle cells and in the contractile myofibrils of skeletal and cardiac muscle. Differences among Tmod family members in expression patterns, TM isoform binding, and actin monomer and polymer regulation suggest unique functions for each of the four vertebrate Tmods. Recent studies of mouse knockouts further implicate key requirements for Tmods and TMs in diverse developmental processes, including striated muscle development, erythrocyte differentiation and stability, and eye lens fiber cell morphogenesis. A central question is: to what extent are common or distinct molecular mechanisms for Tmods’ regulation of actin dynamics utilized to drive unique features of morphogenetic differentiation and development in different tissues? We use a broad spectrum of approaches to answer these questions including molecular, cellular and functional analyses of development in transgenic mice, fluorescence confocal microscopy and 3D image analysis of the actin cytoskeleton in situ in mouse embryos, fluorescence imaging and biochemistry of actin organization and dynamics in cultured cells, and actin polymerization and binding assays with purified proteins in vitro .
Selected References
McKeown, C.R., Nowak, R.B., Moyer, J., Sussman, M.A., and Fowler, V.M. Tropomodulin1 is required in the heart but not the yolk sac for mouse embryonic development. Circ. Res. 103:1241-38, 2008.
Littlefield, R.S. and Fowler, V.M. Thin filament length regulation in striated muscle sarcomeres: Pointed-end dynamics go beyond a nebulin ruler. Sem. Cell Dev. Biol. 19:511-19, 2008.
Weber, K.L., Fischer, R.S. and Fowler, V.M. Tmod3 regulates polarized epithelial cell morphology. J. Cell Sci. 120:3625-32, 2007.
Fischer, R.S. and Fowler, V.M. Tropomodulins: Life at the slow end. Trends Cell Biol. 13:593-601, 2003.
|