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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK074522-04
Application #
7582438
Study Section
Hematopoiesis Study Section (HP)
Program Officer
Wright, Daniel G
Project Start
2006-05-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2009
Total Cost
$304,315
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Belay, Eyayu; Miller, Chris P; Kortum, Amanda N et al. (2015) A hyperactive Mpl-based cell growth switch drives macrophage-associated erythropoiesis through an erythroid-megakaryocytic precursor. Blood 125:1025-33
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