个人简介
教育工作经历:
1997.09-2001.07 厦门大学,学士
2001.09-2006.07 清华大学,博士
2006-12-2008.11 美国匹兹堡大学医学中心 博士后
2008.11-2019.4 美国罗格斯大学新泽西癌症研究所 博士后
2019.11至今 福州大学 “闽江学者”特聘教授
科研简介:
研究方向主要集中在抑癌基因基因p53和肿瘤代谢重编程方面。抑癌基因p53在维持基因组稳定以及抑制肿瘤发生方面有着重要作用。p53是肿瘤中突变频率最高的基因,超过50%的肿瘤包含p53突变,80%以上的肿瘤中p53信号通路功能异常。作为一个转录因子,p53蛋白能被细胞内外各种干扰,包括DNA损伤、缺氧、核糖体合成受阻乃至原癌基因激活等激活,从而进一步选择性的激活其下游的各种目的基因,引起诸如细胞凋亡、细胞周期阻滞以及细胞衰亡等过程,避免细胞癌化。代表性成果包括:
1)发现了两个对肿瘤代谢有重要影响的p53目的基因GLS2和Parkin (PNAS, 2010& 2011, IF:9.504),并在此基础上进一步分析了它们在肿瘤的作用和分子机制,阐明了(a) GLS2通过与Rho GTP酶Rac1的结合降低Rac1活性,抑制由Rac1活性升高引起的肿瘤生长与转移 (Elife, 2016,IF: 7.616);(b) Parkin作为一个E3泛素连接酶,能够结合并机制降解HIF-1α,从而抑制由HIF-1α引起的肿瘤生长与转移为相关肿瘤的治疗提供了新的策略(Nature Communication, 2017, IF: 12.353)。
2)首次报道了肿瘤相关p53突变能够通过改变RhoA活性促进葡萄糖转运蛋白GLUT1向细胞膜上转移,从而增加葡萄糖的吸收和糖酵解,进而促进肿瘤生长,为含有p53突变的肿瘤治疗提供了新思路(Nature Communication, 2013, IF: 12.353)。
3) 抑癌基因CUL3能够与ATP-柠檬酸裂解酶(ACLY)结合,导致其泛素化降解,从而降低细胞脂类合成水平,抑制肿瘤的生长。因此,在CUL3突变或缺失的肺癌中,使用ACLY抑制剂能够有效的减缓肺癌的生长 (Gene & Development, 2016, IF: 9.462)。
科研项目:
1. Parkin调控肿瘤代谢重编程及铁死亡的新分子机制研究(国家自然科学基金面上项目2021-2024)
2. 闽江学者启动基金项目 2020-2023
3. GLS2, a Novel p53 target gene, in liver tumor(美国新泽西癌症研究委员会博士后项目2009-2011)
获奖情况:
2009年2014年 美国新泽西癌症研究委员会 杰出青年科学家Gallo Award
近期论文
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代表性论文:
1. Juan Liu*, Cen Zhang*, Hao Wu, Xiao-Xin Sun, Yanchen Li, Shan Huang, Xuetian Yue, Shou-En Lu, Zhiyuan Shen, Xiaoyang Su, Eileen White, Bruce G Haffty, Wenwei Hu, Zhaohui Feng. Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression. J Clin Invest. 2020, 130:3253-3269. (*: co-first author) (IF:12.772)
2. Juan Liu*, Cen Zhang*, Yuhan Zhao, Xuetian Yue, Hao Wu, Shan Huang, James Chen, Kyle Tomsky, Haiyang Xie, Christen A. Khella, Michael L. Gatza, Dajing Xia, Jimin Gao, Bruce G Haffty, Wenwei Hu, Zhaohui Feng. Parkin targets HIF-1α for ubiquitination and degradation to inhibit tumor progression. Nat Commun, 2017, 8:1823. (*: co-first author) (IF:12.353)
3. Xuetian Yue, Cen Zhang, Yuhan Zhao, Juan Liu, Alan W. Lin, Victor M. Tan, Justin M. Drake, Lianxin Liu, Michael N. Boateng, Jun Li, Zhaohui Feng, Wenwei Hu. Gain-of-function mutant p53 activates Proof Only small GTPase Rac1 through SUMOylation to promote tumor progression. Genes Dev, 2017, 31: 1641-1654.(IF:9.462)
4. Cen Zhang*, Juan Liu*, Grace Huang, Yuhan Zhao, Xuetian Yue, Hao Wu, Jun Li, Junlan Zhu, Zhiyuan Shen, Bruce G Haffty, Wenwei Hu, Zhaohui Feng. Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev, 2016, 30:1956-70. (*: co-first author) (IF:9.462)
5. Cen Zhang*, Juan Liu*, Yuhan Zhao, Xuetian Yue, Yu Zhu, Xiaolong Wang, Hao Wu, Felix Blanco, Shaohua Li, Gyan Bhanot, Bruce G Haffty, Wenwei Hu, Zhaohui Feng. Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis. Elife, 2016, 5:e10727. (*: co-first author) (IF:7.616)
6. Xuetian Yue, Yuhan Zhao, Cen Zhang, Jun Li, Zhen Liu, Juan Liu, Wenwei Hu. Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction. Oncotarget, 2016, 7:3777-3790.(IF:5.168)
7. Yuhan Zhao, Cen Zhang, Xuetian Yue, Xiaoyan Li, Juan Liu, Haiyang Yu, VA Belyi, Qifeng Yang, Zhaohui Feng, Wenwei Hu. Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant p53. Cell Death Differ, 2014, 22:1824-1836. (IF:8.000)
8. Juan Liu*, Cen Zhang*, Xiaolong Wang, P Ly, V Belyi, Zijun Y Xu-Monette, Ken H Young, Wenwei Hu, Zhaohui Feng. E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis. Cell Death Differ, 2014, 21:1792-1804. (*: co-first author) (IF:8.000)
9. Cen Zhang, Juan Liu, Yingjian Liang, Rui Wu, Yuhan Zhao, Xuehui Hong, Meihua Lin , Haiyang Yu, Lianxin Liu, Arnold J. Levine, Wenwei Hu, Zhaohui Feng. Tumor-Associated Mutant p53 Drives the Warburg Effect. Nat. Commun., 2013, 4:2935.(IF:12.353)
10. Zhaohui Feng, Lianxin Liu, Cen Zhang, Tongsen Zheng, Jiabei Wang, Meihua Lin, Yuhan Zhao, Xiaowen Wang, Arnold J. Levined and Wenwei Hu. Chronic restraint stress attenuates p53 function and promotes tumorigenesis. Proc Natl Acad Sci U S A, 2012, 109: 7013-7018. (IF:9.504)
11. Cen Zhang, Meihua Lin, Rui Wu, Xiaowen Wang, Bo Yang, Arnold J. Levine, Wenwei Hu and Zhaohui Feng. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect.Proc Natl Acad Sci U S A, 2011, 108:16259-64.(IF:9.504)
12. Wenwei Hu, Chang S. Chan, Rui Wu, Cen Zhang, Yvonne Sun, Jun S. Song, Laura H. Tang, Arnold J. Levine and Zhaohui Feng. Negative Regulation of Tumor Suppressor p53 by microRNA miR-504. Mol Cell, 2010, 38:689-699.(IF:14.248)
13. Wenwei Hu, Cen Zhang, Rui Wu, Yvonne Sun, Arnold J. Levine and Zhaohui Feng. Glutaminase 2 is a novel p53 target gene regulating energy metabolism. Proc. Natl. Acad. Sci. USA, 2010, 107:7455-7460.(IF:9.504)