Abstract

This application is a request for renewal of our R01 entitled: """"""""A proliferative switch for genetically modified cells,"""""""" which was funded beginning in August 1997. The stated goal of that application was """"""""to apply newly developed technology to the expansion of genetically modified hemopoietic cells in vitro or in vivo."""""""" We have achieved that goal. Our approach uses a derivative of the thrombopoietin receptor (mpl) that delivers a conditional growth signal in response to a drug called a chemical inducer of dimerization (CID).
In specific aim 1 we will humanize the mpl vector.
In specific aim 2 we will test our humanized vector in normal mice and in a mouse model of mpl deficiency.
In specific aim 3 we will test the humanized vector in a canine model.
in specific aim 4 we will test the humanized vector in hemopoietic cells taken from patients with mpl deficiency.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052997-07
Application #
6605792
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
1997-08-10
Project End
2005-05-31
Budget Start
2003-08-01
Budget End
2004-05-31
Support Year
7
Fiscal Year
2003
Total Cost
$271,981
Indirect Cost

  Institution

Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Harkey, Michael A; Kaul, Rajinder; Jacobs, Michael A et al. (2007) Multiarm high-throughput integration site detection: limitations of LAM-PCR technology and optimization for clonal analysis. Stem Cells Dev 16:381-92
Nagasawa, Yasuo; Wood, Brent L; Wang, Linlin et al. (2006) Anatomical compartments modify the response of human hematopoietic cells to a mitogenic signal. Stem Cells 24:908-17
Weinreich, Michael A; Lintmaer, Ingrid; Wang, Linlin et al. (2006) Growth factor receptors as regulators of hematopoiesis. Blood 108:3713-21
Blau, C Anthony; Peterson, Kenneth R (2006) Establishment of cell lines that exhibit correct ontogenic stage-specific gene expression profiles from tissues of yeast artificial chromosome transgenic mice using chemically induced growth signals. Methods Mol Biol 349:163-73
Blau, C Anthony; Barbas 3rd, Carlos F; Bomhoff, Anna L et al. (2005) {gamma}-Globin gene expression in chemical inducer of dimerization (CID)-dependent multipotential cells established from human {beta}-globin locus yeast artificial chromosome ({beta}-YAC) transgenic mice. J Biol Chem 280:36642-7
Richard, Robert E; Siritanaratkul, Noppadol; Jonlin, Erica et al. (2005) Collection of blood stem cells from patients with sickle cell anemia. Blood Cells Mol Dis 35:384-8
Zhao, Shengming; Weinreich, Michael A; Ihara, Kenji et al. (2004) In vivo selection of genetically modified erythroid cells using a jak2-based cell growth switch. Mol Ther 10:456-68
Richard, Robert E; De Claro, R Angelo; Yan, James et al. (2004) Differences in F36VMpl-based in vivo selection among large animal models. Mol Ther 10:730-40
Richard, Robert E; Weinreich, Michael; Chang, Kai-Hsin et al. (2004) Modulating erythrocyte chimerism in a mouse model of pyruvate kinase deficiency. Blood 103:4432-9
Richard, Robert E; Blau, C Anthony (2003) Small-molecule-directed mpl signaling can complement growth factors to selectively expand genetically modified cord blood cells. Stem Cells 21:71-8

Showing the most recent 10 out of 21 publications