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師資隊(duì)伍
侯照遠(yuǎn)
  作者:  2023-03-01

基本信息 >>

                                               
  侯照遠(yuǎn)
  腫瘤微環(huán)境基因表達(dá)調(diào)控研究組

  地址:上海市重慶南路280號西7號樓110室,,200025,上海

  電話:021-63846590-776714
  郵箱:[email protected]

研究方向>>>


   本課題組主要研究方向是在上皮-間質(zhì)細(xì)胞轉(zhuǎn)化(Epithelial-mesenchymal transition, EMT)和腫瘤轉(zhuǎn)移中基因網(wǎng)絡(luò)的表達(dá)與調(diào)控,。具體研究對象是轉(zhuǎn)錄因子Snail抑制基因轉(zhuǎn)錄的分子機(jī)理,。Snail屬于含有SNAG結(jié)構(gòu)域的鋅指(zinc-finger)蛋白家族成員,。SNAG位于Snail分子的氨基端,,具有抑制基因轉(zhuǎn)錄的功能,。在胚胎發(fā)育和腫瘤轉(zhuǎn)移過程中,Snail是誘導(dǎo)EMT的關(guān)鍵因子,,是連接多種促腫瘤轉(zhuǎn)移信號通路的中心分子,。因此,研究Snail在細(xì)胞內(nèi)的作用機(jī)理不僅在理論上有助我們弄清楚腫瘤轉(zhuǎn)移的機(jī)制,,在臨床上也能夠提供新的靶點(diǎn)進(jìn)行藥物設(shè)計(jì)和制定有效的治療方案,。

   當(dāng)前正在對組蛋白精氨酸甲基化在腫瘤轉(zhuǎn)移中的作用進(jìn)行探討。組蛋白精氨酸殘基甲基化對基因的表達(dá)與調(diào)控具有重要作用,。但是相對于其它組蛋白修飾例如磷酸化,,賴氨酸的甲基化等,精氨酸的甲基化研究沒有因以足夠的重視,。精氨酸甲基轉(zhuǎn)移酶VPrmt5)屬于II型精氨酸甲基轉(zhuǎn)移酶,,除了能夠甲基化修飾組蛋白H2AH3H4上的精氨酸殘基,,還能夠修飾非主蛋白底物例如轉(zhuǎn)錄延長因子SPT5,。Prmt5 通過甲基化修飾組蛋白來直接負(fù)調(diào)控基因表達(dá),也能夠用過甲基化修飾來調(diào)控蛋白復(fù)合體的組裝來間接調(diào)控基因表達(dá),。我們前期研究發(fā)現(xiàn)了Snail同過結(jié)合AjubaPrmt5來抑制轉(zhuǎn)錄,,其中Ajuba作為支架蛋白,連接SnailPrmt5共同形成一個(gè)多蛋白復(fù)合體,。


個(gè)人簡歷 >>>

2003年于美國辛辛那提大學(xué)醫(yī)學(xué)院獲生理學(xué)博士學(xué)位,,賓夕法尼亞大學(xué)博士后, Wistar研究所任研究助理(staff scientist),期間曾獲美國國防部Idea Award 專項(xiàng)基金支持,。

20112月回國,,任上海交通大學(xué)醫(yī)學(xué)院生化與細(xì)胞系研究員,基因表達(dá)與調(diào)控課題組長,。主要研究轉(zhuǎn)錄因子在腫瘤發(fā)生和轉(zhuǎn)移的基因網(wǎng)絡(luò)的表達(dá)調(diào)控,,論文發(fā)表在PNASCancer Research,,Nucleic Acid Research等刊物,。

科研項(xiàng)目 >>>

1. 2023年度國家自然科學(xué)基金面上項(xiàng)目

項(xiàng)目批準(zhǔn)號:82273392

項(xiàng)目名稱:Snail激活內(nèi)質(zhì)網(wǎng)未折疊蛋白反應(yīng)(UPR)的分子機(jī)制

起止年限:20231月至202612

資助金額:52萬元

2. 2019年度國家自然科學(xué)基金面上項(xiàng)目

項(xiàng)目批準(zhǔn)號:81872131

項(xiàng)目名稱:去泛素化酶USP29促進(jìn)乳腺癌細(xì)胞轉(zhuǎn)移的分子機(jī)制

起止年限:20191月至202112

資助金額:60萬元

3. 2017年度國家自然科學(xué)基金面上項(xiàng)目

項(xiàng)目批準(zhǔn)號:31671415

項(xiàng)目名稱:LIM 蛋白Ajuba促進(jìn)脂肪細(xì)胞分化的分子機(jī)制

起止年限:20171月至202012

資助金額:62萬元

3. 2015年度上海市國際科技合作基金項(xiàng)目

項(xiàng)目批準(zhǔn)號:15410724200

項(xiàng)目名稱:受Snail調(diào)控的非編碼RNA Lnc00261對胰腺癌發(fā)生和轉(zhuǎn)移的調(diào)控作用研究

起止年限:20161月至201812

資助金額:30萬元

4. 2014年度國家自然科學(xué)基金面上項(xiàng)目

項(xiàng)目批準(zhǔn)號:81372309

項(xiàng)目名稱:硫酰化限速酶PAPSS2Snail誘導(dǎo)EMT和乳腺癌轉(zhuǎn)移中的作用機(jī)理

起止年限:20141月至201712

資助金額:75萬元

5. 2013年度上海市科委基礎(chǔ)研究重大重點(diǎn)項(xiàng)目

項(xiàng)目批準(zhǔn)號:13JC1401302

項(xiàng)目名稱:Snail/Ajuba多蛋白復(fù)合體對子宮內(nèi)膜癌發(fā)生和轉(zhuǎn)移作用研究

起止年限:20139月至20168

資助金額:30萬元

6. 2013年度國家科技部重大研究計(jì)劃(973)子課題

項(xiàng)目名稱:蛋白質(zhì)的賴氨酸修飾在腫瘤發(fā)生重的作用

子課題骨干:侯照遠(yuǎn)

起止年限:20131月至201612

資助金額:85萬元

7. 2012年度上海市浦江人才計(jì)劃(A類)

項(xiàng)目批準(zhǔn)號:12PJ1405700

項(xiàng)目名稱:LIM蛋白Ajuba在乳腺癌激素治療抗性中的作用機(jī)理

起止年限:201210月至20149

資助金額:20萬元

8. 2012年度國家自然科學(xué)基金面上項(xiàng)目

項(xiàng)目批準(zhǔn)號:81172028

項(xiàng)目名稱:精氨酸甲基化修飾在Snail 誘導(dǎo)的EMT 和腫瘤轉(zhuǎn)移中的作用

起止年限:20121月至201512

資助金額:60萬元

論文與專著 >>>


1. Jie Zhang(#); Yuanyuan Yu(#); Xiuqun Zou(#); Yaning Du; Qiankun Liang; Mengyao Gong; Yurong He; Junqi Luo; Dandan Wu; Xiaoli Jiang; Matt Sinclair; Emad Tajkhorshid; Hong-Zhuan Chen; Zhaoyuan Hou(*); Yuejuan Zheng(*); Lin-Feng Chen(*); Xiao-Dong Yang(*). WSB1/2 target chromatin-bound lysinemethylated RelA for proteasomal degradation and NF-κB termination, Nucleic Acids Research, 2024

2. Xiuqun Zou(#), Li Ma(#), Yihong Zhang, Qun Zhang, Chu Xu, Dan Zhang, Yimin Chu, Jie Zhang, Mengying Li, Hui Zhang, Jiamin Wang, Chicheng Peng, Gang Wei, Yingjie Wu(*), Zhaoyuan Hou(*) and Hao Jia(*). GATA zinc finger protein p66β promotes breast cancer cell migration by acting as a co-activator of Snail. Cell Death and Disease, 2023, 14:382 ; https://doi.org/10.1038/s41419-023-05887-w

3. Dan Zhang(#), Yihong Zhang(#), Xiuqun Zou, Mengying Li, Hui Zhang, Yaning Du, Jiamin Wang, Chicheng Peng, Chunyan Dong(*) and Zhaoyuan Hou(*). CHST2-mediated sulfation of MECA79 antigens is critical for breast cancer cell migration and metastasis. Cell Death and Disease, 2023, 14:288 ; https://doi.org/10.1038/s41419-023-05797-x  

4. Linjun Shi(#),Yuquan Yang(#), Mengying Li(#), Chenxi Li, Zengtong Zhou, Guoyao Tang, Lan Wu, Yilin Yao, Xuemin Shen(*), Zhaoyuan Hou(*), Hao Jia(*). LncRNA IFITM4P promotes immune escape by up-regulating PD-L1 via dual mechanism in oral carcinogenesis. Molecular Therapy, 2022, 30(4):1564-1577.

5. Han Yan, Qi Li, Mengying Li, Xiuqun Zou, Ningning Bai, Zichao Yu, Jie Zhang, Dan Zhang, Qun Zhang, Jiamin Wang, Hao Jia(*), Yingjie Wu(*), Zhaoyuan Hou(*). Ajuba functions as a co-activator of C/EBPβ to induce expression of PPARγ and C/EBPα during adipogenesis. Molecular and Cellular Endocrinology, 2022, 539:111485.

6. Hao Jia(#)(*), Yuquan Yang(#), Mengying Li(#), Yimin Chu, Huan Song, Jie Zhang, Dan Zhang, Qun Zhang, Ying Xu, Jiamin Wang, Hong Xu, Xiuqun Zou, Haixia Peng(*), Zhaoyuan Hou(*). Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1. EMBO Reports, 2021, 22: e51780.

7. Jinrui Xu(#), Yuquan Yang(#), Zhaoyuan Hou(*), Hao Jia(*), Yujiong Wang(*). TRPV2-spike protein interaction mediates the entry of SARS-CoV-2 into macrophages in febrile conditions. Theranostics, 2021, 11(15):7379-7390.

8. Zhang P, Zhang Z, Fu Y, Zhang Y, Washburn MP, Florens L, Wu M, Huang C, Hou Z(*), Mohan M(*). K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR. Cell Death Dis. 2021, 12(6):608.

9. Hao Jia(#)(*), Ao Zhang(#), Yuquan Yang, Yaqi Cui, Jianrong Xu, Hewei Jiang, Shengce Tao, Dawei Zhang, Heping Zeng, Zhaoyuan Hou(*), Jijun Feng(*). A graphene oxide coated tapered microfiber acting as a super-sensor for rapid detection of SARS-CoV-2. Lab Chip, 2021, 21:2398–2406.

10. Qian W(#), Li Q(#), Wu X, Li W, Li Q, Zhang J, Li M, Zhang D, Zhao H, Zou X, Jia H, Zhang L(*), Yang XD(*), Hou Z(*). Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein. Oncogene. 2020, 39:6802-6815.

11. Jia H, Peng H, Hou Z. Ajuba: An emerging signal transducer in oncogenesis. Pharmacol Res. 2020, 151:104546.review

12. Bosen Zhang(#), Liwei Song(#), Jiali Cai, Lei Li, Hong Xu, Mengying Li, Jiamin Wang, Minmin Shi, Hao Chen1(*), Hao Jia(*), and Zhaoyuan Hou(*).The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation. J Exp Clin Cancer Res. 2019, 38(1):205.

13. Beihui Xu(#), Qi Li(#), Ning Chen, Chunxiao Zhu, Qingrong Meng, Kasirajan Ayyanathan6 Wenli Qian, Hao Jia, Jiamin Wang(*), Peihua Ni(*), Zhaoyuan Hou(*). The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells. Nucleic Acids Res. 2019, 47(5):2322-2335.

14. Yihong Zhang(#), Xiuqun Zou(#), Wenli Qian, Xiaoling Weng, Lin Zhang, Liang Zhang, Shuang Wang, Xuan Cao, Li Ma, Gang Wei(*), Yingjie Wu(*), Zhaoyuan Hou(*). Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis. Cell Death Differ. 2019, 26:565-579.

15. Yingying Wang(#), Xiaoling Weng(#), Luoyang Wang(#), Mingang Hao, Yue Li, Lidan Hou, Yu Liang, Tianqi Wu, Mengfei Yao, Guowen Lin, Yiwei Jiang, Guohui Fu, Zhaoyuan Hou(*), Xiangjun Meng(*), Jinsong Lu(*), and Jianhua Wang(*). HIC1 deletion promotes breast cancer progression by activating tumor cell/fibroblast crosstalk. J Clin Invest. 2018, 128(12):5235-5250.

16. Jia, H. (#) ; Song, L. (#) ; Cong, Q.; Wang, J.; Xu, H.; Chu, Y.; Li, Q.;Zhang, Y.; Zou, X.; Zhang, C.; Chin, Y. E.; Zhang, X.; Li, Z.; Zhu, K.; Wang,B.; Peng, H. (*) ; Zhaoyuan Hou(*). The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network , Oncogene, 2017, 36(19): 2655-2666.

17. Wang, Xiong-jun (#); Qiao, Yunbo(#) ; Xiao, Minzhe M.; Wang, Lingbo; Chen, Jun; Lv, Wenjian; Xu, Li; Li, Yan; Wang, Yumei; Tan, Ming-dian; Huang, Chao; Li, Jinsong; Zhao, Ting C.; Zhaoyuan Hou (*); Jing, Naihe (*) ; Chin, Y. Eugene(*) , Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells , Cell Rep, 2017, 18(4):933-946.

18. Liu, Chao (#); Wang, Jiamin(#) ; Yuan, Xiaoyuan; Qian, Wenli; Zhang, Bosen; Shi, Minmin; Xie, Junjie; Shen, Baiyong; Xu, Hong (*);Chen, Hao(*); Zhaoyuan Hou(*), Long noncoding RNA uc.345 promotes tumorigenesis of pancreatic cancer by upregulation of hnRNPL expression, Oncotarget, 2016, 7(44): 71556-71566.

19. Li Q (#); H Peng(#) ; H Fan; X Zou; Q Liu; Y Zhang; H Xu; Y Chu; C Wang; K Ayyanathan; FJ Rauscher(*) ; K Zhang (*);Zhaoyuan Hou(*), The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction, Cell Death Differ., 2016, 23(1): 158-168.

20. Hongyan Fan (#); Weibing Dong (#); Qi Li; Xiuqun Zou; Yihong Zhang; Jiamin Wang; Shengxian Li; Wei Liu; Ying Dong; Haipeng Sun (*); Zhaoyuan Hou(*), Ajuba Preferentially Binds LXRα/RXRγ Heterodimer to Enhance LXR Target Gene Expression in Liver Cells, Molecular Endocrinology, 2015, 29(11):1608-1618.

21. Chen Jiangzhi (#); Xu Hong(#); Zou Xiuqun; Wang Jiamin; Zhu Yi; Chen Hao; Shen Baiyong; Deng Xiaxing; Zhou Aiwu; Chin Y. Eugene; Rauscher Frank J.Ⅲ; Peng Chenghong (*); Zhaoyuan Hou(*), Snail Recruits Ring1B to Mediate Transcriptional Repression and Cell Migration in Pancreatic Cancer Cells, Cancer Research, 2014, 74(16): 4353-4363.

22. Peihua Ni (#), Hong Xu (#), Changqiang Chen,  Jiayi Wang, Xiangfan Liu,  Yiqun Hu,  Qishi Fan, Zhaoyuan Hou(*), Yang Lu(*).  Serum starvation induces DRAM expression in liver cancer cells via histone modifications within its promoter locus. PLOS ONE, 2012. 0050502.

23. Zhaoyuan Hou; Hongzhuang Peng; David E. White; Pu Wang; Paul M. Lieberman; Thanos Halazonetis; Frank J. Rauscher Ⅲ(*) , 14-3-3 binding sites in the snail protein are essential for snail-mediated transcriptional repression and epithelial-mesenchymal differentiation, Cancer Research, 2010, 70(11): 4385-4393.

24. Zhaoyuan Hou; Hongzhuang Peng; David E. White; Dmitri G. Negorev; Gerd G. Maul; Yunfeng Feng; Gregory D. Longmore; Samuel Waxman; Arthur Zelent; Frank J. Rauscher Ⅲ(*) , LIM protein Ajuba functions as a nuclear receptor corepressor and negatively regulates retinoic acid signaling, Proc Natl Acad Sci U S A, 2010, 107(7): 2938-2943.

25. Zhaoyuan Hou; Hongzhuang Peng; Kasirajan Ayyanathan; Kaiping Yan; Ellen Langer; Gregory D. Longmore; Frank J. Rauscher Ⅲ(*) , The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression. Molecular and Cellular Biology, 2008, 28(10): 3198-3207.

26. Zhaoyuan Hou, Sunil Srivastava, Meenakshi J. Mistry, Matthew P. Herbst, Jason P. Bailey, Nelson D. Horseman. Two tandemly linked GAS elements in the promoter of glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) gene synergistically respond to prolactin in mouse mammary epithelial cells. Mol Endocrinol, 2003, 17:1910-1920.

27. Zhaoyuan Hou, Bailey JP, Vomachka AJ, Matsuda M, Lockefeer JA, Horseman ND  Glycosylation-dependent cell adhesion molecule 1 is induced by prolactin and suppressed by progesterone in mammary epithelium. Endocrinology, 2000, 141(11): 4278-4283.