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陈航姿副教授

发布时间:2015-10-23来源:点击数:7464

 陈航姿副教授陈航姿 博士

副教授

  +86-592-2880310

E-mail: chenhz@xmu.edu.cn

 

1999.09-2003.06   厦门大学生命科学学院            学士 

2003.09-2009.06   厦门大学生命科学学院            博士

2005.02-2005.09   新加坡国立大学生物科学系    访问学生    

2009.10-2012.07   厦门大学生命科学学院             助理教授

2012.08至今          厦门大学生命科学学院             副教授

 

1999.09-2003.06   School of Life Sciences, Xiamen University     Bachelor 

2003.09-2009.06   School of Life Sciences, Xiamen University     Ph.D

2005.02-2005.09   Department of Biological Sciences, National University of Singapore   

Visiting Students                         

2009.10-2012.07   School of Life Sciences, Xiamen University   Assistant professor

2012.08 up to now  School of Life Sciences, Xiamen University  Associate professor

 

研究领域(Research Area)

我们围绕核受体特别是核孤儿受体TR3(也被称为Nur77NGFI-B)的生物学功能开展研究。TR3在细胞生长、分化、凋亡等过程中发挥着至关重要的作用。由于其特异性配体至今尚未被发现,TR3的翻译后修饰以及其相互作用蛋白被认为是调控TR3生物学功能的重要方式。我们的研究发现TR3可通过对Wnt信号通路的负调控作用,抑制结肠癌的发生。在结肠癌临床标本中,高活性的GSK3β介导TR3发生高度磷酸化,从而阻断了TR3Wnt信号的抑制作用,导致结肠癌的发生。此外,Akt, ERK, Pin1等介导的TR3翻译后修饰也直接影响TR3对细胞生长和凋亡的调控作用。

我们将继续以胃癌、肠癌、肝癌等消化系统肿瘤以及肥胖、糖尿病、高血脂等代谢综合症为研究重点,深入阐明TR3通过对细胞代谢、细胞自噬、细胞凋亡等的调控影响疾病发生的机制,并以TR3为靶点筛选干预这些疾病发生的小分子药物。

We mainly focus on the biological functions of nuclear receptor, especially orphan nuclear receptor TR3 (also known as Nur77 or NGFI-B). TR3 plays an important roles in the processes of cell proliferation, differentiation and apoptosis. Since the specific ligand for TR3 has not been identified till now, the post-translational modifications of TR3 and its binding partners were considered as the main regulatory manner for TR3. We found that TR3 can inhibit growth of colorectal cancer via negatively regulating Wnt singaling activity. In colorectal cancer tissues, highly activated GSK3β induces hyper-phosphorylation of TR3, thereby disrupting the inhibitory effect of TR3 on Wnt signaling and stimulating the tumorigenesis of colorectal cancer. Moreover, Akt, ERK and Pin1 mediated post-translational modifications also influence the regulatory functions of TR3 on cell proliferation and cell death.

We will go on studying the functions of TR3 on digestive system cancer and metabolic syndrome through the regulation on cell metabolism, autophagy and apoptosis, and screening TR3 targeting compounds to interfere the development of this disease.

 

代表性论文(Selected Publications) * Corresponding author  # co-first author

1.     Bian XL#, Chen HZ#, Yang PB#, Li YP#, Zhang FN, Zhang JY, Wang WJ, Zhao WX, Zhang S, Chen QT, Zheng Y, Sun XY, Wang XM, Chien KY, Wu Q*. Nur77 suppresses hepatocellular carcinoma via switching glucose metabolism toward gluconeogenesis through attenuating phosphoenolpyruvate carboxykinase sumoylation. Nature Communications. 2017.8:14420

2.    Li L#, Liu Y#, Chen HZ#, Li FW#, Wu JF, Zhang HK, He JP, Xing YZ, Chen Y, Wang WJ, Tian XY, Li AZ, Zhang Q, Huang PQ, Han J, Lin T*, Wu Q*. Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation. Nature Chemical Biology. 2015, 11(5):339-46.

3.     Chen Y#, Wu R#, Chen HZ, Xiao Q, Wang WJ, He JP, Li XX, Yu XW, Li L, Wang P, Wan XC, Tian XH, Li SJ, Yu X, Wu Q*. Enhancement of hypothalamic STAT3 acetylation by nuclear receptor Nur77 dictates leptin sensitivity. Diabetes. 2015, 64(6):2069-2081.

4.     Wang WJ#, Wang Y#, Chen HZ#, Xing YZ#, Li FW#, Zhang Q, Zhou B, Zhang HK, Zhang J, Bian XL, Li L, Liu Y, Zhao BX, Chen Y, Wu R, Li AZ, Yao LM, Chen P, Zhang Y, Tian XY, Beermann Friedrich, Wu M, Han J, Huang PQ, Lin T*, Wu Q*Orphan nuclear receptor TR3 acts in autophagic cell death of melanoma via a mitochondrial signaling pathwayNature Chemical Biology. 2014, 10:133-140.

5.     Chen HZ*#, Wen Q#, Wang WJ, He JP, Wu Q. The orphan nuclear receptor TR3/Nur77 regulates ER stress and induces apoptosis via interaction with TRAPγ. The International Journal of Biochemistry & Cell Biology,2013, 45:1600 – 1609.

6.     Chen HZ, Li L, Wang WJ, Du XD, Wen Q, He JP, Zhao BX, Li GD, Zhou W, Xia Y, Yang QY, Hew C-L, Liou Y-C*, Wu Q*. Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene 2012, 31:2876-2887.

7.     Chen HZ#, Liu QF#, Li L#, Wang WJ, Yao LM, Yang M, Liu B, Chen Wei, Zhan YY,  Zhang MQ, Cai JC, Zheng ZH, Lin SC, Li BA*, Wu Q*. The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalingGut 2012, 61:714-724.

8.      Zhao BX#, Chen HZ#, Du XD, Luo J, He JP, Wang RH, Wang Y, Wu R, Hou RR, Hong M, Wu Q* Orphan Receptor TR3 Enhances p53 Transactivation and Represses DNA Double-Strand Break Repair in Hepatoma Cells under Ionizing RadiationMolecular Endocrinology 2011, 25: 1337–1350.

9.   Lei NZ#, Zhang XY#, Chen HZ, Wang Yuan, Zhan YY, Zheng ZH, Shen YM, Wu Q*. A feed-back regulatory loop between methyltransferase PRMT1 and orphan receptor TR3. Nucleic Acids Res, 2009; 37, 832-848.

10.   Chen HZ, Zhao BX, Zhao WX, Li L, Zhang B, Wu Q*. Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondriaCarcinogenesis 2008; 29, 2078-2088.

11. Zhan YY#, Du XP#, Chen HZ, Liu JJ, Zhao BX, Huang DH, Li GD, Xu QY, Zhang MQ, Bart C Weimer, Chen D, Cheng Z, Zhang LR, Li QX, Li SW, Zheng ZH, Song SY, Hang YJ, Ye ZY, Su WJ, Lin SC*, Shen YM*, Wu Q*. Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nature Chemical Biology 2008; 4, 548-556.

12. Li GD, Fang JX, Chen HZ, Luo J, Zheng ZH, Shen YM, Wu Q*. Negative regulation of transcription coactivator p300 by orphan receptor TR3. Nucleic Acids Res 2007; 35, 7348-7359.

13.  Chen HZ, Wu Q*. A novel function of p53 in TR3-MDM2 cross-talk. Cell Res 2007; 17(4): 293-4. 


 

荣誉、奖励及参加学术团体的情况(Honors and awards, Professional service

福建省自然科学奖一等奖(排名第二)

First prize of Natural Science Award of Fujian Province (ranked second)

  

福建省青年拔尖创新人才

Youth Top-notch Talent in Fujian province

  

中国病理生理学会肿瘤专业委员会青年委员

Youth member of the tumor professional committee ofChinese Association of Pathophysiology