徐曉玲教授

Education
PhD	Department of Physiology, University of Maryland, Medical School, Baltimore, USA. (2002)
MSc	Institute of Hydrobiology, Academia Sinica, Wuhan, China (1987)
BSc	Department of Biology, West China Normal University, Nanchong, China (1982)

Positions
20223 – Present	Visiting Professor, Faculty of Health Sciences, University of Macau
2014 – 2023	Associate Professor, Faculty of Health Sciences, University of Macau
1999 – 2014	Staff Scientist, Mammalian Genetics Section, Genetics of Development and Disease Branch, NIDDK
1995 – 1999	Visiting associate, Genetics of Development and Disease Branch, NIDDK
1992 – 1995	Visiting associate, Whitehead Institute for Biomedical Research, MIT, Nine Cambridge Center, Cambridge, MA 02142.
1987 – 1992	Research associate, Department of Pathology, University of Utah

Research Interests
Tumor suppressors Smad4, and Pten in mammalian development and tumorigenesis.  Breast cancer associated gene 1 (BRCA1) in mammary gland development and tumorigenesis  Interactions between estrogen signaling and BRCA1 in DNA replication and genome stability

Representative Publications

Eicher, Eva M., Washburn, Linda L., Schork, Nicholas J., Lee, Barbara K., Shown, Elanie P., Xiaoling Xu, Dredge, Robert K., Pringle, M. Jodeane & Page, David C (1996). Sex-determining genes on mouse autosomes identified by linkage analysis of C57BL/B6J-Ypos sex reversal. Nature Genetics 14, 206-209. Xiaoling Xu, Michael Weinstein, Cuiling Li, Michael Naski, Rick I. Cohen, David M. Ornitz, Philip Leder and Chuxia Deng (1998). Fibroblast growth factor receptor 2 (FGFR2) mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125, 753-765. Xiaoling Xu, Michael Weinstein, Cuiling Li and Chu-Xia Deng (1999). Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell&Tissue Research, 296, 33-43. Xiaoling Xu, Zoë Weaver, Steven P. Linke, Cuiling Li, Jessica Gotay, Xin-Wei Wang, Curtis C. Harris, Thomas Ried and Chu-Xia Deng (1999). Centrosome Amplification and a Defective G2-M Checkpoint Induce Genetic Instability in BRCA1 Exon 11 Isoform-Deficient Cells. Molecular Cell 3, 389-396. Xiaoling Xu, Cuiling Li, Katsu Takahashi, Harold C. Slavkin, Lillian Shum and Chuxia Deng (1999). Murine Fibroblast Growth Factor Receptor 1 Alpha (FGFR1) Isoforms Mediate Node Regression and Are Essential for Posterior Mesoderm Development. Developmental Biology, 208, 293-306. Xiaoling Xu, Kay-Uwe Wagner, Cuiling Li, Anthony Wynshaw-Boris, Lothar Hennighausen and Chu-Xia Deng (1999). Conditional knockout of BRCA1 in mammary glands results in abnormal ductal morphogenesis and tumor formation. Nature Genetics, 22, 37-43. Xiaoling Xu, Steven G. Brodie, Xiao Yang, Young-Hyuck Im, W. Tony Parks, Lin Chen, Yong-Xing Zhou, Jian-Wu Xie, Seong-Jin Kim and Chuxia Deng. (2000). Haploinsufficiency of the tumor suppressor Smad4/Dpc4 initiates gastrointestinal polyposis and cancer in mouse. Oncogene. 2000 19(15):1868-74. Xiaoling Xu, Cuiling Li, Lisa Garrett-Beal, Denise Larson, Anthony Wynshaw-Boris, and Chu-Xia Deng. (2001). Direct removal in the mouse of a floxed neo gene from a three-loxP conditional knockout allele by two novel approaches. Genesis, 30(1):1-6. Xiaoling Xu, Wenhui Qiao, Steven P. Linke, Wen-Mei Li, Cuiling Li, Pricilla A. Furth, Curtis C. Harris, and Chu-Xia Deng. (2001). Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle, genomic stability and tumorigenesis. Nature Genetics 28, 266-271. Xaioling Xu, Wenhui Qiao, Cuiling Li, and Chuxia Deng (2002). Generation of Fgfr1 conditional knockout mice. Genesis, 32, 85-6. Xiaoling Xu (corresponding author), Olga Aprelikova, Peter Moens, Chuxia Deng, and Priscilla A. Furth (2003). Impaired meiotic DNA damage repair and lack of crossing over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development. 30, 2001-12. James MA Turner*, Olga Aprelikova*, Xiaoling Xu* (*equal contribution), Ruihong Wang, Sangsoo Kim, Paul S Burgoyne, and Chuxia Deng (2004). BRCA1 interacts with ATR and H2AX and plays an essential role in meiotic sex chromosome inactivation during spermatogenesis. Current Biology. 14(23):2135-42. Chuxia Deng, and Xiaoling Xu (2004). Generation and analysis of Brca1 conditional knockout mice. Methods Mol Biol. 280:185-200. James MA Turner, Shantha K Mahadevaiah, Fernandez-Capetillo O, Nussenzweig A, Xiaoling Xu, Chuxia Deng and Paul S Burgoyne (2005). Silencing of unsynapsed meiotic chromosomes in the mouse. Nature Genetics. 37(1):41-7. Ruihong Wang, Cuiling Li, Xiaoling Xu, Yin Zheng, Cuiying Xiao, Patricia Zerfas, Sharon Cooperman, Michael Eckhaus, Tracey Rouault, Lope Mishra, and Chuxia Deng. (2005). A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metabolism. 2(6):399-409. Xiaoling Xu, S. Kobayashi, W. Qiao, C. Li, C. Xiao, S. Radaeva, B. Stiles, R.H. Wang, N. Ohara, T. Yoshino, D. LeRoith, M.S. Torbenson, G.J. Gores, H. Wu, B. Gao and Chuxia Deng (2006). Induction of intrahepatic cholangiocellular carcinoma by liver specific disruption of Smad4 and Pten in mice. Journal of Clinic Investigation, 116(7):1843-1852. Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, Kim SS, Xiaoling Xu, Zheng Y, Chilton B, Jia R, Zheng ZM, Appella E, Wang XW, Ried T, and Chuxia Deng (2008). Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell 14, 312–323. Wang RH, Zheng Y, Kim HS, Xiaoling Xu, Cao L, Luhasen T, Lee MY, Xiao C, Vassilopoulos A, Chen W, Man YG, Hung MC, Finkel T, and Chuxia Deng (2008). Interplay among BRCA1, SIRT1, and SURVIVIN during BRCA1-associated Tumorigenesis. Mol. Cell 32, 11–20. Jie Liu*, Liu Cao* (*Equal contribution), Jichun Chen, Shiwei Song, In Hye Lee, Bong-Hyun Ahn, Neil G. Kumar, Long-Yue Cao, Hongjun Liu, Ilsa I. Rovira, Keyvan Keyvanfar, Xiaoling Xu, Maarten van Lohuizen, Noboru Motoyama, Chu-Xia Deng and Toren Finkel (2009). Deletion of Bmi1 activates a redox-sensitive DNA damage response pathway. Nature, 459(7245):387-92. Liu Cao, Xiaoling Xu, Samuel F. Bunting, Rui-Hong Wang, Jie Liu, Longyue L. Cao, Junjie Chen, Andre Nussenzweig, Chu-Xia Deng* (*Corresponding author) and Toren Finkel* (*Corresponding author) (2009). A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Molecular Cell, 35(4):534-41. Xiaoling Xu, Beeta Ehdaie, Nobuya Ohara, Tadashi Yoshino, and Chu-Xia Deng (2010). Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in mice. Oncogene, 4;29(5):674-86. Samuel Bunting, Nancy Wong, Hua-Tang Chen, Federica Polato, Oscar Fernandez-Capetillo, Jeremy M. Stark, Liu Cao, Xiaoling Xu, Chu-Xia Deng, Toren Finkel, Elsa Callén1, André Nussenzweig (2010). Loss of 53BP1 rescues homologous recombination in Brca1-deficient cells. Cell, 141(2):243-54. Su N*, Xiaoling Xu * (Equal contribution), Li C, He Q, Zhao L, Li C, Chen S, Luo F, Yi L, Du X, Huang H, Chu-Xia Deng*, Chen L* (Corresponding author). (2010). Generation of Fgfr3 conditional knockout mice, Int J Biol Sci. 6(4):327-32. Hyun-Seok Kim, Cuiying Xiao, Rui-Hong Wang, Tyler Lahusen, Xiaoling Xu, Athanassios Vassilopoulos, Guelaguetza Vazquez-Ortiz, Won-Il Jeong, Ogyi Park, Sung Hwan Ki, Bin Gao, and Chu-Xia Deng. (2010). Hepatic specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metabolism, 12(3):224-36. Hyun-Seok Kim, Athanassios Vassilopoulos, Rui-Hong Wang, Tyler Lahusen, Zhen Xiao, Xiaoling Xu, Cuiling Li, Timothy D. Veenstra, Bing Li, Hongtao Yu, Junfang Ji, Xin Wei Wang, Seong-Hoon Park, Yong I. Cha, David Gius, and Chu-Xia Deng. (2011). SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. Cancer Cell, 20, 487–499. Seung Min Jeong* (equal contribution), Cuiying Xiao* (equal contribution), Lydia W.S Finley, Tyler Lahusen, Amanda L. Souza, Kerry Pierce, Ying-Hua Li, Xiaoxu Wang, Gaëlle Laurent, Natalie J. German, Xiaoling Xu, Cuiling Li, Rui-Hong Wang, Jaewon Lee, Alfredo Csibi, Richard Cerione, John Blenis, Clary B. Clish, Alec Kimmelman, Chu-Xia Deng* (Corresponding authors) & Marcia C. Haigis* (Corresponding authors) (2013). SIRT4 is a tumor suppressor that regulates cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell, 23(4):450-63. Wang Rui Hong, Tyler Lahusen, Qiang Chen, Xiaoling Xu, Lisa Miller Jenkins, Elisabetta Leo, Hai Qing Fu, Mirit Aladjem, Yves Pommier, Ettore Appella, and Chu Xia Deng. (2014) SIRT1 deacetylates TopBP1 and modulates intra-S-phase checkpoint and DNA replication origin firing. Int J Biol Sci 10 (10), 1193-1202 Li Yu Ying, N Hong, A Zhang, W Chen, RH Wang, Xiaoling Xu, and Chu Xia Deng. (2014) Enhancing mammary differentiation by overcoming lineage-specific epigenetic modification and signature gene expression of fibroblast-derived iPSCs. Cell Death Dis 5 (12), e1550 Cristine L Chisholm, Haitao Wang, Ada Hang-Heng Wong, Guelaguetza Vazquez-Ortiz, Weiping Chen, Xiaoling Xu, Chu-Xia Deng. (2016). Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin. Oncotarget. 7(51):84439-84452. Takaaki Masuda, Xiaoling Xu, Emilios K Dimitriadis, Tyler Lahusen, Chu-Xia Deng. (2016). “DNA Binding Region” of BRCA1 Affects Genetic Stability through modulating the Intra-S-Phase Checkpoint. Int J Biol Sci. 12(2):133-43. Hongping Zheng, Fangyuan Shao, Scots Martin, Xiaoling Xu, and Chu-Xia Deng. (2017). WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance. Scientific Reports. Mar 6;7:43517. Qiang Chen, Wenhui Hao, Cuiying Xiao, Ruihong Wang, Xiaoling Xu, Huiyan Lu, Weiping Chen, Chu-Xia Deng (2017). SIRT6 is Essential for Adipocyte Differentiation through Regulating Mitotic Clonal Expansion. Cell Reports. Mar 28;18(13):3155-3166. Liu J, Adhav R, Xiaoling Xu (2017). Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research. Int J Biol Sci. Jul 18;13(8):949-960. Wei Xu, Fengtao Luo, Quan Wang, Qiaoyan Tan, Junlan Huang, Siru Zhou, Zuqiang Wang, Xianding Sun, Liang Kuang, Min Jin, Nan Su, Wanling Jiang, Liang Chen, Huabing Qi, Ying Zhu, Bo Chen, Hangang Chen, Shuai Chen, Yu Gao, Xiaoling Xu, Chuxia Deng, Lin Chen, Yangli Xie, Xiaolan Du. (2017). Inducible Activation of FGFR2 in Adult Mice Promotes Bone Formation After Bone Marrow Ablation. J Bone Miner Res. 32(11):2194-2206. Chen Qiang, Wen Hui Hao, Cui Ying Xiao, Rui Hong Wang, Xiaoling Xu, Hui Yan Lu, Wei Pin Chen, and Chu Xia Deng. (2017) SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion. Cell Rep 18 (13), 3155-3166 Tyler J. Lahusen, Seung-Jin Kim, Kai Miao, Zebin Huang, Xiaoling Xu, and Chu-Xia Deng. (2018). BRCA1 function in the intra-S checkpoint is activated by acetylation via a pCAF/SIRT1 axis. Oncogene, Apr;37(17):2343-2350. LFengtao Luo, Yangli Xie, Zuqiang Wang, Junlan Huang, Qiaoyan Tan, Xianding Sun, Fangfang Li, Can Li, Mi Liu, Dali Zhang, Meng Xu, Nan Su, Zhenhong Ni, Wanling Jiang, Jinhong Chang, Hangang Chen, Shuai Chen, Xiaoling Xu, Chuxia Deng, Zhugang Wang, Xiaolan Du, Lin Chen. (2018). Adeno-Associated Virus-Mediated RNAi against Mutant Alleles Attenuates Abnormal Calvarial Phenotypes in an Apert Syndrome Mouse Model. Mol Ther Nucleic Acids. 13:291-302. Baoyuan Zhang, Junfang Lyu, Yifan Liu, Changjie Wu, Eun Ju Yang, Lakhansing Pardeshi, Kaeling Tan, Koon Ho Wong, Qiang Chen, Xiaoling Xu, Chu-Xia Deng, Joong Sup Shim. (2018). BRCA1 deficiency sensitizes breast cancer cells to bromodomain and extra-terminal domain (BET) inhibition. Oncogene. 37(49):6341-6356. Heng Sun, Zhengqiang Miao, Xin Zhang, Un In Chan, Sek Man Su, Sen Guo, Chris Koon Ho Wong, Xiaoling Xu, Chu-Xia Deng. (2018). Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia. J Biol Chem. 293(22):8315-8329. Xiaoling Xu* (*Corresponding author), Eric Chen, Lihua Mo, Lei Zhang, Fangyuan Shao, Kai Miao, Jianlin Liu, Sek Man Su, Monica Valecha, Un In Chan, Hongping Zheng, Mark Chen, Weiping Chen, Qiang Chen, Haiqing Fu, Mirit I Aladjem, Yanzhen He, Chu-Xia Deng* (*Corresponding author). (2018). BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy. Hum Mol Genet. 28(5):842-857. Tan Qiao Yan, Bo Chen, Quan Wang, Wei Xu, Yuan Qiang Wang, Zhi Hua Lin, Feng Tao Luo, Shuo Huang, Ying Zhu, Nan Su, Min Jin, Can Li, Liang Kuang, Hua Bing Qi, Zheng Hong Ni, Zu Qiang Wang, Xiao Qing Luo, Wan Ling Jiang, Han Gang Chen, Shuai Chen, Fang Fang Li, Bin Zhang, Jun Lan Huang, Ruo Bin Zhang, Ke Xin Jin, Xiaoling Xu, Chu Xia Deng, Xiao Lan Du, Yang Li Xie, and Lin Chen (2018). A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice. Osteoarthritis Cartilage 26 (12), 1733-1743 Miao Kai, Xin Zhang, Sek Man Su, Jian Ming Zeng, Ze Bin Huang, Un In Chan, Xiaoling Xu* (*Corresponding author), and Chu Xia Deng* (*Corresponding author) (2019). Optimizing CRISPR/Cas9 technology for precise correction of the Fgfr3-G374R mutation in achondroplasia in mice. J Biol Chem 294 (4), 1142-1151 Sun Xian Ding, Ruo Bin Zhang, Mi Liu, Han Gang Chen, Liang Chen, Feng Tao Luo, Da Li Zhang, Jun Lan Huang, Fang Fang Li, Zhen Hong Ni, Hua Bing Qi, Nan Su, Min Jin, Jing Yang, Qiao Yan Tan, Xiao Lan Du, Bo Chen, Hai Yang Huang, Shuai Chen, Liang Jun Yin, Xiaoling Xu, Chu Xia Deng, Ling Fei Luo, Yang Li Xie, and Lin Chen (2019). Rmrp mutation disrupts chondrogenesis and bone ossification in zebrafish model of cartilage-hair hypoplasia via enhanced Wnt/beta-catenin signaling. J Bone Miner Res 34 (11), 2101-2116 Chen Qiang, Josh Hai Peng Lei, Jiao Lin Bao, Hai Tao Wang, Wen Hui Hao, Licen Li, Cheng Peng, Takaaki Masuda, Kai Miao, Jun Xu, Xiaoling Xu, and Chu Xia Deng (2020). BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis. Adv Sci, 14;7(6):1903616. Xiao Lian, Ting Ting An, Lin Wang, Xiaoling Xu, and Han Dong Sun (2020). Novel properties and applications of chiral inorganic nanostructures. Nano Today 30, 100824 Zhang Bao Yuan, Jun Fang Lyu, Eun Ju Yang, Yi Fan Liu, Chang Jie Wu, Lakhansing Pardeshi, Kae Ling Tan, Qiang Chen, Xiaoling Xu, Chu Xia Deng, and Joong Sup Shim (2020). Class I histone deacetylase inhibition is synthetic lethal with BRCA1 deficiency in breast cancer cells. Acta Pharm Sin B 10 (4), 615-627 Miao Kai, Josh Hai Peng Lei, Monica Vishnu Valecha, Ai Ping Zhang, Jun Xu, Li Jian Wang, Xue Ying Lyu, Si Chen, Zheng Qiang Miao, Xin Zhang, Sek Man Su, Fang Yuan Shao, Barani Kumar Rajendran, Jiao Lin Bao, Jian Ming Zeng, Heng Sun, Ping Chen, Kae Ling Tan, Qiang Chen, Koon Ho Wong, Xiaoling Xu, and Chu Xia Deng (2020). NOTCH1 activation compensates BRCA1 deficiency and promotes triple-negative breast cancer formation. Nat Commun 11 (1), 3256 Liu Jian Lin, Ragini Adhav, Kai Miao, Sek Man Su, Li Hua Mo, Un In Chan, Xin Zhang, Jun Xu, Jian Jie Li, Xiao Dong Shu, Jian Ming Zeng, Xu Zhang, Xueying Lyu, Lakhansing Pardeshi, Kae Ling Tan, Heng Sun, Koon Ho Wong, Chu Xia Deng, and Xiaoling Xu (2020). Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor. Nat Commun 11 (1), 4875 Haitao Wang, Sen Guo, Seung-Jin Kim, Fangyuan Shao, Joshua Wing Kei Ho, Kuan Un Wong, Zhengqiang Miao, Dapeng Hao, Ming Zhao, Jun Xu, Jianming Zeng, Koon Ho Wong, Lijun Di, Ada Hang-Heng Wong, Xiaoling Xu, Chu-Xia Deng (2021). Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel. Theranostics, 2021; 11(5): 2442-2459. Licen Li, Jiaolin Bao, Haitao Wang, Haipeng Lei, Cheng Peng, Jianming Zeng, Wenhui Hao, Xu Zhang, Xiaoling Xu, Chundong Yu, Chu-Xia Deng and Qiang Chen (2021). Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation. Theranostics, 2021; 11 (4): 1672-1689. Jun Xu, Sek Man Su, Xin Zhang, Un In Chan, Ragini Adhav, Xiaodong Shu, Jianlin Liu, Jianjie Li, Lihua Mo, Yuqing Wang, Tingting An, Josh Haipeng Lei, Kai Miao, Chu-Xia Deng, Xiaoling Xu* (2022). ATP11B inhibits breast cancer metastasis in a mouse model by suppressing externalization of non-apoptotic phosphatidylserine. Journal of Clinical Investigation, 2022; 132 (5): e149473. Jianjie Li, Xiaodong Shu, Jun Xu, Sek Man Su, Un In Chan, Lihua Mo, Jianlin Liu, Xin Zhang, Ragini Adhav, Qiang Chen, Yuqing Wang, Tingting An, Xu Zhang, Xueying Lyu , Kai Miao, Chuxia Deng*, Xiaoling Xu * (2022). S100A9-CXCL12 Axis in BRCA1 Deficiency Orchestrates the Immunosuppressive Microenvironment to Enable Breast Cancer Resistant to Immune Checkpoint Blockade. Nature Communications. 2022; 13:1481.

Awards
2011	NIDDK Director’s Award: “In recognition of extraordinary research in understanding mechanisms of BRCA1 and its transcriptional downstream genes in cancer, cell cycle, genetic stability, aging and metabolism”
2002	The finalist of Research Excellency for Graduate Study in the Washington DC-Baltimore area
2001	A recipient of the seventh annual NIH-wide FARE 2001 (Research Excellency) awards