Dr. YangXin Fu is currently appointed as Associate Professor in the Division of Experimental Oncology in the Faculty of Medicine and Dentistry.
Oncology 320, Oncology 425, and Discovery Learning
Our group has two main areas of interest: (1) Molecular mechanisms governing the tumorigenic phenotypes in ovarian cancer (signaling pathways and gene regulation) and (2) the impact of rRNA methylations on mRNA translation and the tumorigenic phenotypes in glioblastoma. Project 2: To determine the functional impact of rRNA methylations on mRNA translation and the tumorigenic phenotypes in glioblastoma. Glioblastoma is the most common and aggressive malignant primary brain tumor. The median survival of adults with glioblastoma is about 14.6 months even with aggressive surgical resection, radiation and chemotherapy. We need to better understand the molecular mechanisms underlying the initiation and progression of glioblastoma to develop novel therapeutics. Cancer cells have unique (specialized) and heterogeneous ribosomes that favors translation of subsets of mRNA associated with tumor initiation and/or progression. The objective of this project is to determine how rRNA methylations alter ribosome biogenesis and structure, thereby affecting mRNA translation and the tumorigenic phenotypes in glioblastoma.
Project 1: To determine the molecular mechanisms governing the tumorigenic phenotypes in ovarian cancer. Current therapeutic regimens against advanced ovarian cancer are ineffective due to recurrent therapy resistant disease, driven at least in part by tumor heterogeneity. There is an urgent need to determine the molecular mechanisms by which the tumorigenic phenotypes are regulated, which will help identify potential novel therapeutic targets to treat ovarian cancer. This project is to study transcriptional regulation of the genes that are critical for cancer stem cells, proliferation, and metastasis in ovarian cancer. High throughput approaches (RNA-sequencing and ChIP-sequencing), as well as, in vitro and in vivo models are used to tackle this question.
Cancer stem cells, Chemoresistance, Glioblastoma, Notch pathway, Ovarian cancer, RNA methylation, RNA methyltransferase, Signaling pathway
- Huachen Chen, Powel Crosley, Abul K Azad, Nidhi Gupta, Nisha Gokul, Zhihua Xu, Michael Weinfeld, Lynne-Marie Postovit, Stephanie A. Pangas, Mary M. Hitt, YangXin Fu*, RUNX3 promotes the tumorigenic phenotype in KGN, a human granulosa cell tumor-derived cell line, International Journal of Molecular Sciences, 20(14), 3471, 2019
- Xiaolu Han, Huachen Chen, Jiesi Zhou, Helen Steed, Lynne-Marie Postovit, YangXin Fu*, Pharmacological inhibition of p38 MAPK by SB203580 increases resistance to carboplatin in A2780cp cells and promotes growth in primary ovarian cancer cells, International Journal of Molecular Sciences, 19(8), 2184, 2018
- Jiesi Zhou, Saket Jain, Abul K Azad, Xia Xu, Hai chuan Yu, Zhihua Xu, Roseline Godbout, YangXin Fu*. Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cells, Cellular Siganlling, 28(8):838-49, 2016
- Ahmed El-Sehemy, Lynne-Marie Postovit, YangXin Fu*, Nitric oxide signaling in human ovarian cancer: a potential therapeutic target, Nitric Oxide, 54, 30-37, 2016
- Samir Barghout, Nubia Zepeda, Zhihua Xu, Helen Steed, Cheng-Han Lee, YangXin Fu*, Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells, Biochemical and Biophysical Research Communications, 468, 173-178, 2015
- Samir Barghout, Nubia Zepeda, Krista Vincent, Abul Kalam Azad, Zhihua Xu, Christine Yang, Helen Steed, Lynne Postovit, YangXin Fu*, RUNX3 contributes to the chemoresistance of epithelial ovarian cancer cells, Gynecologic Oncology, 138(3), 647-655, 2015 7.
- Jennifer L. Ali, Brittany J. Lagasse, Ainsley J. Minuk, Allison J. Love, Gilbert Arthur, Spencer B. Gibson, Ludivine Coudière Morrison, Tamra E. Werbowetski-Ogilvie, YangXin Fu, Mark W. Nachtigal, Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and –resistant human epithelial ovarian cancer cells, International Journal of Cancer, 136(5):E455-69, 2015.
- Abul Kalam Azad, Subhadeep Chakrabarti, Zhihua Xu, Sandra T. Davidge, YangXin Fu*, Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-α/nuclear factor κB-induced endothelial inflammation, Cellular Signalling, 26(12): 2793-2800, 2014.
- Ahmed El-Sehemy, Alex Chang, Abul Kalam Azad, Nidhi Gupta, Zhihua Xu, Helen Steed, Aly Karsan, YangXin Fu*, Notch activation augments nitric oxide/soluble guanylyl cyclase signaling in immortalized ovarian surface epithelial cells and ovarian cancer cells, Cellular Signalling, 25(12):2780-2787, 2013.
- Nidhi Gupta, Zhihua Xu, Ahmed El-Sehemy, Helen Steed, YangXin Fu*, Notch3 induces epithelial-mesenchymal transition and attenuates carboplatin-induced apoptosis in ovarian cancer cells, Gynecologic Oncology, 130(1), 200-206, 2013.
- Chang AC, YangXin Fu, Garside VC, Niessen K, Chang L, Fuller M, Setiadi A, Smrz J, Kyle A, Minchinton A, Marra M, Hoodless PA, and Karsan A, 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, Michèle 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
- Zhihua Xu, Yanyan Jiang, Helen Steed and Sandra Davidge, YangXin Fu*, TGFβ and EGF synergistically induce a more invasive phenotype of epithelial ovarian cancer cells, Biochemical and Biophysical Research Communications, 401, 376-381, 2010
- Yangxin Fu, Alex Chang, Linda Chang, Kyle Niessen, Shawn Eapen, Audi Setiadi, and Aly Karsan, Differential regulation of TGFβ 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
- Yangxin Fu, Laura M. O’Connor, Trevor G. Shepherd, and Mark W. Nachtigal, The p38 MAPK Inhibitor, PD169316, Inhibits Transforming Growth Factor ß (TGFß) Induced Smad Signaling in Human Ovarian Cancer Cells, Biochemical and Biophysical Research Communications, 310, 391-397, 2003
- Yangxin Fu, Elizabeth J. Campbell Dwyer, Trevor G. Shepherd, and Mark W. Nachtigal, Epigenetic Regulation of Proprotein Convertase PACE4 Gene Expression in Human Ovarian Cancer Cells. Molecular Cancer Research, 1, 569-76, 2003
- Yangxin Fu, Helmut Sies, and Xingen Lei, Opposite roles of selenium-dependent glutathione peroxidase-1 in superoxide generator diquat- and peroxynitrite-induced apoptosis and signaling. Journal of Biological Chemistry, 276, 43004-43009, 2001
Characterizing cancer stem cells in granulosa cell tumors (GCT) and their role in resistance
- Funding Source: Granulosa Cell Tumor Research Foundation
- Year Granted: 2018
- Research Role: Principal Investigator