The goal of this application is to test a candidate 'universal' cell growth switch, a conditional derivative of the fibroblast growth factor receptor 1, F36VFGFR1, in preclinical models of gene and cell therapy.
In specific aim 1, we will test whether different growth factor receptor signaling domains differentially regulate human hemopoiesis.
In specific aim 2 we will compare the nature, intensity and duration of the hematopoietic response to F36VFGFR1 signaling versus F36Vmp1 signaling in dogs.
In specific aim 3 we will test whether F36VFGFR1 signaling promotes self-renewal in engineered human embryonic stem (ES) cells. We will be using the human embryonic stem cell line WA01.
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| Kacherovsky, Nataly; Harkey, Michael A; Blau, C Anthony et al. (2012) Combination of Sleeping Beauty transposition and chemically induced dimerization selection for robust production of engineered cells. Nucleic Acids Res 40:e85 |
| Okazuka, Kiyoshi; Beard, Brian C; Emery, David W et al. (2011) Long-term regulation of genetically modified primary hematopoietic cells in dogs. Mol Ther 19:1287-94 |
| Weinreich, Michael A; Lintmaer, Ingrid; Wang, Linlin et al. (2006) Growth factor receptors as regulators of hematopoiesis. Blood 108:3713-21 |
