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YangXin Fu Adjunct Assistant Professor Experimental Oncology Department of Oncology University of Alberta 5-142M Katz Group Centre 114 Street & 87 Avenue Edmonton, Alberta T6G 2E1 Tel: 780.248.1363 yangxin@ualberta.ca Profile The objective of the Fu laboratory is to better understand the molecular mechanisms underlying ovarian tumorigenesis, with a particular interest in the role of Notch signaling pathway in ovarian cancer development and progression.   Ovarian cancer is the fifth leading cause of cancer deaths in women and the leading cause of gynecologic cancer-related death. The high mortality is due to the lack of effective methods for early detection of ovarian cancer. Despite advances in surgical techniques and chemotherapy regimens, relapse will occur in patients with advanced ovarian cancer. Patients become less responsive to chemotherapy with each subsequent relapse due to the development of drug resistance. Thus there is an urgent need to understand the molecular pathogenesis for this heterogeneous disease and to identify potential signaling pathways as therapeutic targets.   Notch signaling determines cell fate by regulating multiple processes such as differentiation, proliferation and apoptosis. Notch signaling pathway has been associated with human cancers and proposed as potential therapeutic target for several types of cancer. We will utilize tissue culture, molecular and cell biology approaches as well as mouse models to investigate whether activation of Notch signaling plays a role in ovarian cancer development and progression, and to identify the underlying molecular mechanisms.   The undergoing projects include 1) determining the role of Notch activation in ovarian cancer using in vitro and in vivo models, 2) identifying downstream effectors of Notch signaling in ovarian cancer cells, and 3) studying how Notch interacts with other signaling pathways in ovarian cancer. We hope that our research can lead to a better treatment for ovarian cancer in the future.     Publications Alex C.Y. Chang, YangXin Fu, Victoria C. Garside, Kyle Niessen, Linda Chang, Megan Fuller, Audi Setiadi, Justin Smrz, Alastair Kyle, Andrew Minchinton, Marco Marra, Pamela A. Hoodless, and Aly Karsan, Notch Initiates the Endothelial-to-Mesenchymal Transition in the Atrioventricular Canal through Autocrine Activation of Soluble Guanylyl Cyclase, Developmental Cell, 21(2):288-300, 2011   YangXin Fu, Alex Chia YU Chang, Michele Fournier, Linda Chang, Kyle Niessen and Aly Karsan, Runx3 maintains the mesenchymal phenotype after termination of the Notch signal, Journal of Biological Chemistry, 286, 11803-13, 2011 (Epub 2011 Feb 2)   Zhihua Xu, Yanyan Jiang, Helen Steed, Sandra Davidge, and YangXin Fu*, TGFβ and EGF synergistically induce a more invasive phenotype of epithelial ovarian cancer cells, Biochemical and Biophysical Research Communications, 401, 371-381, 2010. (*Corresponding author)   YangXin Fu, Alex Chang, Linda Chang, Kyle Niessen, Shawn Eapen, Audi Setiadi, and Aly Karsan, Differential regulation of TGF b signaling pathways by Notch in human endothelial cells. Journal of Biological Chemistry, 284 , 19452-19462, 2009   Kyle Niessen, YangXin Fu, Pamela Hoodless, Debroah McFadden, and Aly Karsan, Slug is a direct Notch target required for initiation of cardiac cushion cellularlization. Journal of Cell Biology, 182, 315-325, 2008   Michela Noseda, Yangxin Fu, Kyle Niessen, Fred Wong, Linda Chang, Graeme McLean and Aly Karsan, Smooth muscle alpha-actin is a direct target of Notch/CSL. Circulation Research, 98, 1468-1470, 2006