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Research Interests:The focus of the lab is to understand how regulators of stem cells and lineage commitment in the mammary gland can contribute to breast cancer. We use the mouse mammary gland as a model system because its accessibility allows the use of gold standard assays such as limiting dilution and serial transplantations. The fact that these techniques measure stem cell activity in vivo is especially important considering the strict regulation of stem cell activity by surrounding cells and systemic cues from the environment. We investigate selected candidate regulators of stem cells, and subsequently study their role in mammary stem cells, lineage commitment and overall mammary gland development. For those candidates that show interesting phenotypes, we study the causal involvement in tumorigenesis by modulating their levels in normal, predisposed and tumor cells. An important tool to determine the effects of our genes of interest on the different lineages of the mammary stem cell hierarchy is the FACS Sorter with 4 lasers (analysis up to 12 colors) that we operate in the lab. Currently we are analyzing the role of T-box repressors and Wip1 phosphatase in mammary stem cells and breast cancer. For most recent information see: www.pietersenlab.com. Selected Publications:Puppe, J., Drost, R., Liu, X., Joosse, S.A., Evers, B., Cornelissen-Steijger, P., Nederlof P., Yu, Q., Jonkers, J.*, van Lohuizen, M.* and Pietersen, A.M.* (2009) BRCA1-deficient mammary tumors cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A. Breast Cancer Res, 11:R63. *equal contribution Pietersen, A.M.*, Horlings, H.M.*, Hauptmann, M., Langerød, A., Ajouaou, A., Cornelissen-Steijger, P., Wessels, L.F., Jonkers, J., Vijver, M.J., and van Lohuizen, M. (2008). EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer. Breast Cancer Res, 10:R109.*equal contribution Pietersen, A.M., Evers, B., Prasad, A.A., Tanger, E., Cornelissen-Steijger, P., Jonkers, J., and van Lohuizen, M. (2008). Bmi1 regulates stem cells and proliferation and differentiation of committed cells in mammary epithelium. Curr Biol, pp. 1094-1099. Pietersen, A.M., and van Lohuizen, M. (2008). Stem cell regulation by polycomb repressors: postponing commitment. Curr Opin Cell Biol, pp. 201-207. |
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