Assistant Professor, Department of Cell Biology
My lab is interested in two interlocking areas of stem cell biology: the molecular pathways that regulate the normal stem-cell state in the mammary gland, and the role of these pathways in the regulation of breast cancer stem cells.
Regulators of mammary stem cells
We have developed sensitive and specific mammary stem cell assays. Using these assays, we aim to identify novel markers and regulators of mammary stem cells.
In this effort, we identified two key transcription factors of mammary stem cells, Slug and Sox9. Both factors are necessary for maintaining endogenous mammary stem cells. Furthermore, ectopic expression of these factors efficiently converts differentiated mammary epithelial cells into long-term gland-regenerating stem cells. We are now investigating the mechanism of action by which these factors induce stem cells and regulate the epithelial cell hierarchy in the mammary gland.
Function of stem-cell pathways in breast cancer
Emerging evidence suggests that normal stem-cell pathways often get activated aberrantly in cancers and contribute to aggressive cancer behaviors. Identification of key normal stem cell regulators provides us a framework to understand how breast cancer stem cells are regulated. We are particularly interested in understanding the role of stem-cell factors in regulating metastatic colonization, a rate-limiting step of the metastatic cascade that involves cancer stem cells. In addition, we are interested in how cancer stem cells are regulated by the tumor microenvironment.
1- Guo W, Pylayeva Y, Pepe A, Yoshioka T, Muller WJ, Inghirami G, Giancotti FG. (2006) Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 126: 489-502.
2- Mani SA*, Guo W*, Liao MJ*, Eaton EN, Ayyanan A, Zhou A, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campell LL, Polyak K, Brisken C, Yang J, Weinberg RA. (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133: 704-715. (*: equal contribution.)
3- Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. (2008) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology 26: 795-797.
4- Scheel C, Eaton EN, Li SH, Chaffer CL, Reinhardt F, Kah KJ, Bell G, Guo W, Rubin J, Richardson AL, Weinberg RA. (2011) Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 145: 926-940.
5- Guo W, Keckesova Z, DonaherJ, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zürrer-Härdi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA. (2012) Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 148: 1015-1028.
More Information About Dr. Wenjun Guo
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Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 122
Bronx, NY 10461