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WENJUN GUO, Ph.D. Positions: Assistant Professor, Department of Cell Biology, Member, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research Albert Einstein College of Medicine Research interests: Our research focuses on the role of stem/progenitor cell fate dysregulation in breast cancer pathogenesis. One area of our work is related to the cell-of-origin of breast cancer. How do heterogeneous subtypes of breast cancer arise remains largely unclear. Addressing this question is important for breast cancer prevention and treatment. Distinct stem/progenitor cell populations have recently been identified in the mammary gland. It is likely that accumulation of genetic/epigenetic mutations in different cell types leads to distinct tumor subtypes. Thus we are elucidating the normal mammary stem/progenitor cell hierarchy and heterogeneity and applying this understanding to dissect breast cancer cell-of-origin. The second area of our work is to understand the role of cellular reprogramming in cancer initiation and progression and dissect the mechanism mediating such changes. Non-stem cells can be reprogrammed in vivo to a stem-like state and contribute to cancer development. We are investigating the effect of cancer driver mutations and tissue microenvironment in disrupting proper cell fate determination and inducing stem -like cells. Our long-term goal is to identify unique molecular characteristics and vulnerabilities of these aberrant cell types to enable development of more effective preventive and therapeutic strategies. Current grant funding: NYSTEM/IIRP C029571 06/01/2014-05/31/2017 Role of Mammary Stem/Progenitor Cell Regulator Sox9 in Basal-Like Breast Cancer The V Foundation for Cancer Research / V Scholar Award 11/01/2014-10/31/2016 Role of novel breast cancer mutations in cell fate dysregulation and oncogenesis Five recent publications: 1. 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. The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704–15. (* equal contribution) 2. Scheel C, Eaton EN, Li SH, Chaffer CL, Reinhardt F, Kah KJ, Bell G, Guo W, Rubin J, Richardson AL, Weinberg RA. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 2011, 145:926–40. 3. Guo W, Keckesova Z, Donaher J, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zürrer-Härdi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 2012, 148:1015–28. 4. T a m WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA. Protein kinase C is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell 2013, 24: 347 – 364. 5. Guo W. Breast cancer stem cells: regulatory networks, stem cell niches, and disease relevance. Stem Cells Translational Medicine 2014, 3:942-948.