職務：研究員/碩士生導師/所長

學歷：博士

電子郵件： bixingzhao@gmail.com

主要研究方向：腫瘤相關細胞信號轉導通路、免疫治療與精準醫學方面的基礎與臨床轉化研究

教育工作經歷：

1999/09 - 2003/07，廈門大學，生物科學， 本科

2003/09 - 2006/07，廈門大學，細胞生物學，碩士

2006/09 - 2011/04，廈門大學，細胞生物學，博士

2011/04 - 2014/12，廈門大學附屬中山醫院，博士后

2014/08 - 2014/11，美國德克薩斯州立大學圣安東尼奧健康科學中心，訪問學者

2015/01 - 至今，福建醫科大學孟超肝膽醫院，副研究員，研究員

2017/09 – 2022/12，福建醫科大學孟超肝膽醫院肝病研究所，副所長

2017/06 - 至今，福州大學孟超醫學與交叉科學中心，副教授、碩士生導師

2022/12 – 至今，福建醫科大學孟超肝膽醫院肝病研究所，所長

教學簡介：

參與承擔本科生課程《腫瘤生物學》教學。

科研簡介：主要從事腫瘤相關細胞信號轉導通路、免疫治療與精準醫學方面的基礎與臨床轉化研究。主持國家自然科學基金面上項目、科技部重點專項等多項國家級和省市級研究課題。在The EMBO Journal, Signal Transduction and Targeted Therapy, Theranostics等國際知名期刊上發表SCI收錄論文四十多篇。入選福建省第二批“雛鷹計劃”青年拔尖人才，福建省百千萬人才工程省級人選，福建省高層次人才（C類）；曾獲得福建省科技進步一等獎、福建省自然科學一等獎、廈門市科學技術進步一等獎、福州市青年科技獎、福建醫學科技獎、福建省抗癌協會科技進步一等獎等榮譽。

社會兼職：福建省醫學會肝病學分會青年委員會副主任委員、中國抗癌協會抗癌藥物專業委員會委員、中國醫師協會中西醫結合醫師分會基礎與轉化醫學專業委員會委員、中國醫藥生物技術協會科研實驗室建設與管理分會委員、福建省藥理學會腫瘤藥理專業委員會常委、中華醫學會肝病學分會肝病基礎醫學與實驗診斷協作組成員、福建省醫學會外科學分會實驗外科及轉化醫學學組委員。

科研項目：

1. 福建省科技創新聯合資金項目（2021Y9032），環狀RNA腫瘤新抗原疫苗在腫瘤免疫治療中的應用研究，2022/10-2025/10，100萬，主持。

2. 福建省中央引導地方科技發展資金項目（2022L3030），肝癌免疫逃逸相關lncRNA調控網絡研究(福建省肝膽胰腫瘤臨床醫學研究中心)，2022/08-2025/08，40萬，主持。

3. 福建省衛生教育聯合攻關計劃項目（2019-WJ-19），長鏈非編碼RNA FAM99A在缺氧誘導的肝癌轉移中的作用及機制研究，2019/09-2022/09，20萬，主持。

4. 福建省衛生健康中青年骨干人才培養項目（2020GGA072），METTL16通過調控LncRNA AC079360.1 m6A甲基化促進肝癌侵襲轉移，2021/01-2023/12，10萬，主持。

5. 福州市衛生健康系統科技計劃創新團隊培育項目（2021-S-wt2），長鏈非編碼RNA Lnc-PLA2G4A-4通過miR-23b/Versican信號軸調控肝癌的侵襲轉移，2021/09-2024/09，8萬，主持。

6. 國家自然科學基金面上項目（81672376），SALL4及其相互作用蛋白對肝癌治療抗性的調控功能研究，2017/01-2020/12，57萬，主持。

7. 國家重點研發計劃“科技助力經濟2020”重點專項（SQ2020YFF0426513），病毒性肝炎相關肝癌人群預警和早篩試劑研發，2020/07-2022/6，100萬，合作主持。

8. 福州市衛生計生系統科技計劃創新團隊培育項目(2017-S-wt2)，Ku80通過SALL4調控肝癌細胞干性，2017/08-2020/07，8萬，主持。

9. 福建省醫學創新課題（2016-CX-48） SALL4在肝癌細胞DNA損傷修復中的作用研究，2016/10-2019/09，12萬，主持。

10. 福建省自然科學基金面上項目（2016J01417），10-23 型脫氧核酶靶向SALL4 抑制肝癌細胞侵襲轉移的實驗研究，2016/04-2019/04，5萬，主持。

11. 福州市科技計劃項目（2015-S-143-19），靶向SALL4基因的microRNA對人肝癌細胞惡性表型的影響，2015/04-2018/03，3萬，主持。

12. 國家自然科學基金青年項目（81302069），Cx32通過p53信號通路調控肝癌細胞侵襲轉移，2014/01-2016/12，24萬，主持。

13. 中國博士后科學基金面上項目（2013M531550），CX32通過p53和Akt信號通路調控肝癌細胞增殖與侵襲轉移，2013/01-2015/01，5萬，主持。

14. 福建省自然科學基金青年創新項目（2012D055），細胞連接蛋白connexin32在肝癌發生發展中的作用研究，2012/07-2013/11，4萬，主持。

已發表論文：（*為通訊作者）

(1) Lin Y, Wang F, Zhong Y, Cheng NM, Xiong J, Zheng X, Zhou Y, Gao S, Li F, Wang Y, Yang X, Zhao B*. Long non-coding RNA COX7C-5 promotes hepatocellular carcinoma progression via miR-581/ZEB2 axis. Cellular Signalling. 2023; 101: 110501.

(2) You S, Luo Z, Cheng N, Wu M, Lai Y, Wang F, Zheng X, Wang Y, Liu X, Liu J, Zhao B*. Magnetically responsive nanoplatform targeting circRNA circ_0058051 inhibits hepatocellular carcinoma progression. Drug Delivery and Translational Research. 2023;13:782-794

(3) Bixing Zhao#, Kun Ke#, Yingchao Wang#, Fei Wang#, Yingjun Shi, Xiaoyuan Zheng, Xiaoyu Yang, Xiaolong Liu*, Jingfeng Liu*, HIF-1α and HDAC1 mediated regulation of FAM99A-miR92a signaling contributes to hypoxia induced HCC metastasis. Signal Transduction and Targeted Therapy. 2020; 5:118

(4) Liu J, Wang F, Zhang Y, Liu J, Zhao B*. ADAR1-Mediated RNA Editing and Its Role in Cancer. Front Cell Dev Biol. 2022;10:956649

(5) Ying Sun#, Xiaoyuan Zheng#, Hui Yuan, Geng Chen, Jiahe Ouyang, Jingfeng Liu, Xiaolong Liu, Xiaohua Xing*, Bixing Zhao*, Proteomic Analyses Reveal Divergent Ubiquitylation Patterns in Hepatocellula Carcinoma Cell Lines With Different Metastasis Potential. Journal of proteomics. 2020;225:103834.

(6) Bixing Zhao#, Yingchao Wang#, Xionghong Tan, Kun Ke, Cuilin Zhang, Yunzhen Gao, Naishun Liao, Yuan Dang, Yingjun Shi, Youshi Zheng, Xiaolong Liu*, Jingfeng Liu*, An optogenetic controllable T cell system for hepatocellular carcinoma immunotherapy. Theranostics. 2019; 9(7): 1837-1850.

(7) Bixing Zhao; Yingchao Wang; Xionghong Tan; Kun Ke; Xiaoyuan Zheng; Fei Wang; Shubing Lan; Naishun Liao; Zhixiong Cai; Yingjun Shi; Youshi Zheng; Yongping Lai; Lili Wang; Qin Li; Jingfeng Liu; Aimin Huang*; Xiaolong Liu*; Inflammatory Micro-environment Contributes to Stemness Properties and Metastatic Potential of HCC via the NF-kappaB/miR-497/SALL4 Axis. Molecular therapy oncolytics. 2019; 15, 79-90

(8) Bixing Zhao#, Xiaoyuan Zheng#, Xionghong Tan, Kun Ke, Fei Wang, YingchaoWang, Xiaohua Xing, Cuilin Zhang, Ping Hu, Shubing Lan, Qin Li, Aimin Huang*,  Xiaolong Liu*. Ku80 negatively regulates the expression of OCT4 via competitive binding to SALL4 and promoting lysosomal degradation of OCT4. The International Journal of Biochemistry & Cell Biology. 2020,118: 105664.

(9) Xing X, Yuan H, Sun Y, Ke K, Dong X, Chen H, Liu X, Zhao B*, Huang A*. ANXA2Tyr23 and FLNASer2152 phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis. Journal of proteomics. 2019, 200:111-122.

(10) Hongzhi Liu#, Hui Chen#, Xiaomo Wu, Ying Sun, Yingchao Wang, Yongyi Zeng , Geng Chen, Xiaolong Liu, Xiaohua Xing*, Bixing Zhao*, Jingfeng Liu, The serum proteomics tracking of hepatocellular carcinoma early recurrence following radical resection. Cancer Management and Research. 2019;11: 2935-2946

(11) Shubing Lan, Xiaoyuan Zheng, Ping Hu, Xiaohua Xing, Kun Ke, Fei Wang, Niangmei Cheng, Qiuyu Zhuang, Xiaolong Liu, Jingfeng Liu, Bixing Zhao*, Yingchao Wang*. Moesin facilitates metastasis of Hepatocellular carcinoma cells by improving invadopodia formation and activating β-catenin/MMP9 axis. Biochemical and Biophysical Research Communications. 2020; 524(4):861-868.

(12) Youshi Zheng#, Naishun Liao#, Yuan Wu, Ju Gao, Zhenli Li, Wenwen Liu, Yingchao Wang, Ming Li, Xiaolou Li, Li Chen, Wenmin Zhang*, Bixing Zhao*, High expression of B7H2 or B7H3 is associated with poor prognosis in hepatocellular carcinoma, Molecular Medicine Reports. 2019; 19: 4315-4325.

(13) B. Zhao, W. Zhao, Y. Wang, Y. Xu, J. Xu, K. Tang, S. Zhang, Z. Yin, Q. Wu, and X. Wang*, Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways. Oncotarget, 2015. 6(12): p. 10116-33.

(14) B. Zhao, H. Chen, X. Du, J. Luo, J. He, R. Wang, Y. Wang, R. Wu, R. Hou, M. Hong, and Q. Wu*, Orphan receptor TR3 enhances p53 transactivation and represses DNA double-strand break repair in hepatoma cells under ionizing radiation. Molecular Endocrinology, 2011. 25(8): 1337-50.

(15) B. Zhao, H. Chen, N. Lei, G. Li, W. Zhao, Y. Zhan, B. Liu, S. Lin, and Q. Wu*, p53 mediates the negative regulation of MDM2 by orphan receptor TR3. The EMBO journal, 2006. 25(24): 5703-15.

(16) X.Lin^#, B. Zhao^#, H. Chen, X. Ye, C. Yang, H. Zhou, M. Zhang, S. Lin, and Q. Wu, RXRalpha acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells. J Cell Sci, 2004. 117(Pt 23):5609-21.

(17) 邢曉華，袁暉，趙必星*. NEDD8抑制劑MLN4924抑制肝細胞癌惡性表型的研究.山西醫科大學學報,2021,52:123-128.

(18) 王珊,王菲,鄭曉源,趙必星*. 靶向SALL4脫氧核酶抑制肝細胞癌惡性表型的實驗研究.山西醫科大學學報,2019(11):1499-1504.

(19) 賴永平,曾金華,譚雄紅,柯坤,趙必星*,成簇規律間隔的短回文重復序列及其相關蛋白9敲除Ku80基因提高HEK293T細胞對阿霉素的敏感性, 中華實驗外科雜志, 2018, 35(8): 1437-1440.

(20) Liao N, Su L, Zheng Y, Zhao B, Wu M, Zhang D, Yang H, Liu X, Song J. In Vivo Tracking of Cell Viability for Adoptive Natural Killer Cell-Based Immunotherapy by Ratiometric NIR-II Fluorescence Imaging. Angew Chem Int Ed Engl. 2021;60(38):20888-20896.

(21) Liu H, Lin S, Ao X, Gong X, Liu C, Xu D, Huang Y, Liu Z, Zhao B, Liu X, Han X, Ye H. Meta-analysis of transcriptome datasets: An alternative method to study IL-6 regulation in coronavirus disease 2019. Comput Struct Biotechnol J. 2021;19:767-776.

(22) Xing X, Yuan H, Liu H, Tan X, Zhao B, Wang Y, Ouyang J, Lin M, Liu X, Huang A. Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma. Genomics Proteomics Bioinformatics. 2021;19(1):94-107.

(23) Zhong Y, Yang Y, He L, Zhou Y, Cheng N, Chen G, Zhao B, Wang Y, Wang G, Liu X. Development of Prognostic Evaluation Model to Predict the Overall Survival and Early Recurrence of Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021;8:301-312.

(24) Qiao S, Xin F, Wu M, Zheng Y, Zhao B, Zhang C, Liu X, Wei Z, Liu J. A remotely controlled NIR-II photothermal-sensitive transgene system for hepatocellular carcinoma synergistic therapy. J Mater Chem B. 2021;9(25):5083-5091.

(25) Xiaohua Xing, Hui Yuan, Ying Sun, Kun Ke, Xiuqing Dong, Hui Chen, Xiaolong Liu, Bixing Zhao, Aimin Huang. Dataset for quantitative phospho-proteomics analysis of a serial hepatoma cell lines with increasing invasion and metastasis potential. Data in Brief, 2019; 27:104634.

(26) Naishun Liao, Yingjun Shi, Yingchao Wang, Fangyu Liao, Bixing Zhao, Youshi Zheng, Yongyi Zeng, Xiaolong Liu, Jingfeng Liu. Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model. Stem Cell Res Ther. 2020;11(1):237.

(27) Lin X, Huang Y, Sun Y, Tan X, Ouyang J, Zhao B, Wang Y, Xing X, Liu J. 4E-BP1Thr46 Phosphorylation Association with Poor Prognosis in Quantitative Phosphoproteomics of Portal Vein Tumor Thrombus Revealed that 4E-BP1Thr46 Phosphorylation is Associated with Poor Prognosis in HCC. Cancer Management and Research, 2020, 12: 103-115.

(28) Liuping Luo, Lihong Chen, Kun Ke, Bixing Zhao, Lili Wang, Cuilin Zhang, Fei Wang, Naishun Liao, Xiaoyuan Zheng, Xiaolong Liu, Yingchao Wang, Jingfeng Liu, High Expression Levels of CLEC4M Indicate Poor Prognosis in Patients With Hepatocellular Carcinoma. Oncol Lett. 2020;19(3):1711-1720.

(29) Y Wang#, G Wang#, X Tan#, K Ke, B Zhao, N Cheng, Y Dang, N Liao, F Wang, X Zheng, Q Li, X Liu*, J Liu*. MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53. Oncogenesis, 2019, 8(12):67.

(30) Liao, N., Shi, Y., Zhang, C., Zheng, Y., Wang, Y., Zhao, B., Zeng, Y., Liu, X., and Liu, J. Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion. Stem cell research & therapy. 2019; 10:306

(31) Zhang Xiang; Wang Fei; Huang Yanbing; Ke Kun; Zhao Bixing; Chen Lihong; Liao Naishun; Wang Lei; Li Qin; Liu Xiaolong; Wang Yingchao & Liu Jingfeng. FGG promotes migration and invasion in hepatocellular carcinoma cells through activating epithelial to mesenchymal transition. Cancer Management and Research. 2019;11:1653-1665

(32) Liu Z, Wu S, Wang L, Kang S, Zhao B, He F, Liu X, Zeng Y, Liu J. Prognostic Value of MicroRNA-497 in Various Cancers: A Systematic Review and Meta-Analysis. Dis Markers. 2019, 2019: 2491291.

(33) Ke K, Chen G, Cai Z, Huang Y, Zhao B, Wang Y, Liao N, Liu X, Li Z, Liu J. Evaluation and prediction of hepatocellular carcinoma prognosis based on molecular classification. Cancer management and research, 2018, 10: 5291-5302.

(34) Yan, S., Cui, S., Ke, K., Zhao, B., Liu, X., Yue, S., & Wang, P. Hyperspectral stimulated Raman scattering microscopy unravels aberrant accumulation of saturated fat in human liver cancer. Analytical chemistry. 2018; 90: 6362?6366

(35) Wu, M., Lin, X., Tan, X., Li, J., Wei, Z., Zhang, D., Zheng, Y., Zheng, A., Zhao, B., ... & Liu, X. Photo-responsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin to Optimize and Enhance Synergistic Therapy of Multidrug-resistant Cancer. ACS applied materials & interfaces. 2018, 10(23): 19416-19427.

(36) Wu, M., Li, J., Lin, X., Wei, Z., Zhang, D., Zhao, B., ... & Liu, J. Reduction/photo dual-responsive polymeric prodrug nanoparticles for programmed siRNA and doxorubicin delivery. Biomaterials science. 2018, 6(6): 1457-1468.

(37) Liao, N., Zheng, Y., Xie, H., Zhao, B., Zeng, Y., Liu, X., & Liu, J. Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats. Stem cell research & therapy. 2017,8(1): 286.

(38) Wei, Z., Lin, X., Wu, M., Zhao, B., Lin, R., Zhang, D. Zhang, Y., Liu, G., Liu, X. & Liu, J. Core-shell NaGdF 4@ CaCO 3 nanoparticles for enhanced magnetic resonance/ultrasonic dual-modal imaging via tumor acidic micro-enviroment triggering. Scientific Reports, 2017, 7(1): 5370.

(39)W. Chen, L. Chen, Z. Cai, D. Liang, B. Zhao, Y. Zeng, X. Liu, and J. Liu, Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma. Tumour Biol, 2016, 37(7):9343-55

(40) W. Zhao, Y. Xu, J. Xu, D. Wu, B. Zhao, Z Yin, and X. Wang. Subsets of myeloid-derived suppressor cells in hepatocellular carcinoma express chemokines and chemokine receptors differentially. Int Immunopharmacol. 2015. 26(2): 314-21.

(41) W. Zhao, L. Zhang, Y. Xu, Z. Zhang, G. Ren, K. Tang, P. Kuang, B. Zhao, Z. Yin, and X. Wang, Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab Invest, 2014. 94(2): 182-91.

(42) W. Wang, Y. Wang, H. Chen, Y. Xing, F. Li, Q. Zhang, B. Zhou, H. Zhang, J. Zhang, X. Bian, L. Li, Y. Liu, B. Zhao, Y. Chen, R. Wu, A. Li, L. Yao, P. Chen, Y. Zhang, X. Tian, F. Beermann, M. Wu, J. Han, P. Huang, T. Lin, and Q. Wu, Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014. 10(2): 133-40.

(43) R. Wang, J. He, M. Su, J. Luo, M. Xu, X. Du, H. Chen, W. Wang, Y. Wang, N. Zhang, B. Zhao, W. Zhao, Z. Shan, J. Han, C. Chang, and Q. Wu, The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling. EMBO Mol Med, 2013. 5(1): 137-48.

(44) H. Chen, L. Li, W. Wang, X. Du, Q. Wen, J. He, B. Zhao, G. Li, W. Zhou, Y. Xia, Q. Yang, C. Hew, Y. Liou, and Q. Wu, Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene, 2012. 31(23): 2876-87.

(45) Y. Zhan, X. Du, H. Chen, J. Liu, B. Zhao, D. Huang, G. Li, Q. Xu, M. Zhang, B. Weimer, D. Chen, Z. Cheng, L. Zhang, Q. Li, S. Li, Z. Zheng, S. Song, Y. Huang, Z. Ye, W. Su, S. Lin, Y. Shen, and Q. Wu, Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nat Chem Biol, 2008. 4(9): 548-56.

(46) H. Chen, B. Zhao, W. Zhao, L. Li, B. Zhang, and Q. Wu, Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. Carcinogenesis, 2008. 29(11): p. 2078-88.

(47) W. Zhao, M. Tian, B. Zhao, G. Li, B. Liu, Y. Zhan, H. Chen, and Q. Wu, Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X receptor-alpha. Mol Endocrinol, 2007. 21(12): 2877-89.

授權發明專利：

（1）發明人：劉小龍，趙必星，劉景豐，譚雄紅. 一種光調控T細胞活化的表達載體、構建方法及應用. 授權號：201610404536.9, 授權日期：20200110, 專利權人: 福州市傳染病醫院

獲獎情況

福建省科技進步一等獎，《肝癌微創與診療一體化技術的研究及應用》，排名第9，2022

福建省抗癌協會科技進步獎一等獎，《肝細胞癌復發轉移分子標志物篩選及機制研究》，排名第1，2022

福州市最美科技工作者，2022

百千萬人才工程省級人選，2021

福建省第二批“雛鷹計劃”青年拔尖人才，2021

第四屆福州青年科技獎，2020

福建省自然科學獎一等獎，《孤兒受體TR3通過信號轉導通路抑制腫瘤細胞生長的新機制》，排名第4，2013

廈門市科技進步一等獎，《原發性肝癌的基礎與臨床應用研究》，排名第8，2012