Understanding the dynamic interaction between kinases and phosphates is a critical biochemical mechanism in the control of cytoplasmic signaling that mediates blood cell development. Much of the information passed from cell surface receptor-ligand interaction to the nucleus is transmitted via phosphorylated proteins. We wish to understand the molecular basis and signal transduction pathways responsible for the commitment and differentiation of hematopoietic stem/progenitor cells. We intend to address this question by investigating the role of Shp-2, a protein tyrosine phosphatase, in hematopoiesis. We will determine the role of Shp-2 in mediating the development of a common precursor for hematopoietic and endothelial cells. We will also determine the significance of the ras-Erk kinase pathway in mediating Shp-2 control of hematopoiesis Our ultimate goal is that the findings from these studies will allow for the development of improved and less toxic therapies for human leukemias.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA084677-03
Application #
6514337
Study Section
Special Emphasis Panel (ZRG1-HEM-2 (01))
Program Officer
Lohrey, Nancy
Project Start
2002-05-01
Project End
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
3
Fiscal Year
2002
Total Cost
$54,352
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Li, Yanjun; McClintick, Jeanette; Zhong, Li et al. (2005) Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood 105:635-7
Chan, Rebecca J; Johnson, Scott A; Li, Yanjun et al. (2003) A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis. Blood 102:2074-80
Guo, Ying; Chan, Rebecca; Ramsey, Heather et al. (2003) The homeoprotein Hex is required for hemangioblast differentiation. Blood 102:2428-35
Xie, Xiaodong; Chan, Rebecca J; Yoder, Mervin C (2002) Thrombopoietin acts synergistically with LIF to maintain an undifferentiated state of embryonic stem cells homozygous for a Shp-2 deletion mutation. FEBS Lett 529:361-4
Palis, J; Chan, R J; Koniski, A et al. (2001) Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis. Proc Natl Acad Sci U S A 98:4528-33