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.
| 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 |
