肿瘤病毒学研究组

20161107143140674067.jpg负责人:屠红  

博士,研究员,博士研究生导师

Prof. Hong Tu  M.D.& Ph.D., Doctoral supervisor

屠红,女,1966年4月出生。1990年毕业于上海医科大学,获博士学位。1999年至2001年在法国巴斯德研究所INSERM U370从事博士后研究工作。曾在上海医科大学微生物学教研室、美国南加州大学医学院霍华德休斯研究院和美国路易斯安娜州立大学PBRC研究所工作。现任上海市肿瘤研究“癌基因及相关基因国家重点实验室”课题组长,研究员,博导。主要从事肝癌的病毒病因学和高危人群的预测预警工作,以及神经精神因素对恶性肿瘤的系统调控研究。先后负责国家自然科学基金面上项目、上海市科委重大项目、“十二五”、“十三五”国家科技重大专项等科研项目,研究成果获国家教委科技进步一等奖(第二排名)、上海中西医结合科学技术三等奖(第二排名)及中-法科技协会生物技术奖等奖项。发表论文90余篇,其中SCI收录45篇,参编中、英文论著5部,获国家发明专利授权3项。担任《World Journal of Gastroenterology》、《肿瘤》等杂志编委,上海市抗癌协会传统医学专业委员会委员。

 

 

主要研究方向

1.乙型肝炎病毒(HBV)相关肝癌的预警模型开发和早期诊断研究;

2.肝癌和肝外肿瘤的HBV病因学研究;

3.外周肿瘤的整体系统性调控及机制研究。

 

Section of Molecular Virology

 

Hong Tu, MD, Ph.D, professor of basic medical science at Stated Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, is a medically trained researcher with graduate training in molecular virology at Shanghai Medical University and the University of Southern California, and postgraduate training in cell biology at INSERM U370, Necker/Pasture institute, France. Dr. Tu has worked as a principal investigator in Shanghai Cancer Institute for more 10 years. Before, she was a research instructor in Penning Biomedical Research Institute, Louisiana State University, USA and a lecturer in Shanghai Medical University. As a principal investigator, Dr. Tu has completed several projects supported by Nation Natural Science of China projects, Chinese State Key Project Specialized for Infectious Diseases and Shanghai Municipal Science and Technology Commission. She has published more than 90 papers in peer-reviewed journals and has been granted 3 patents. She is the editorial board of the journal Tumor and World Journal of Gastroenterology, and serves as the referee of several national and international journals.

 

Research Interests

1Development of novel predictive models for the early diagnosis of HBV-related hepatocellular carcinoma;

2The etiologic role of HBV in the development of hepatocellular carcinoma and other primary cancers;

3Holistic effects on peripheral cancers and the underlying mechanisms.

 

研究团队成员:

Current Team Members:

甘愉  博士,副研究员,硕士研究生导师

Yu Gan  Ph.D. , Associated Professor, Master supervisor

金晏  学士,主管技师,实验室管理

Yan Jin  B.Sc., Technologist-in-charge, Lab manager

袁慧  博士,助理研究员

Hui Yuan  Ph.D., Research Associate

姜敬慧  硕士,实习研究员

Jinghui Jiang  M.Sc., Research Assistant

 

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主要承担及参与课题  

 

课题标题

编号

负责人

起止时间

类别

城市人群HBV相关肝癌的前瞻性流行病学研究及基于HBV 变异的启东肝癌风险模型的验证及应用

2012ZX10002008-002

项永兵、屠红

2012.01-2015.12

国家科技重大专项

胰腺癌中乙肝病毒整合及整合靶基因MLL4的插入诱变机制研究

81572312

 

2016.01-2019.12

国自然面上

丰富生存环境增强NK细胞抗肿瘤免疫的作用及机制研究

81571618

甘愉

2016.01-2019.12

国自然面上

良性心理应激抑制肿瘤作用及其免疫调控机制:基于丰富生存环境小鼠肿瘤模型的研究

81201823

甘愉

2013.01-2015.12

国自然青年

丰富生存环境通过ABC转运蛋白调控胰腺癌化疗敏感性的作用及机制研究

81502601

袁慧

2016.01-2018.12

国自然青年

 

 发明专利

 

专利名称

授权号

授权日期

国别

发明人

一种用于肝癌血清学诊断的单克隆抗体及其用途

ZL201010200883.2

2013.12.25

中国

屠红、陈敏、张菁

检测乙型肝炎病毒前C/C区变异的试剂盒及方法

ZL201010144732.X

2013.12.11

中国

屠红,朱宇,金晏,钱耕荪

一种用于诊断肝癌的ELISA试剂盒

ZL200710039562.7

2012.08.08

中国

屠红, 周伟, 赵新泰

 
主要研究成果

 

I 肝癌及肝外肿瘤的HBV病因学研究

在我国肝癌患者中,90%以上的人具有乙肝病毒(HBV)感染的证据。近年来的研究还提示了HBV感染和一些肝外肿瘤如胰腺癌、淋巴瘤等也显著相关。本课题组致力于从HBV病毒角度探索肝癌以及肝外HBV相关肿瘤发生发展的分子机制,为预防和诊治提供新的策略和靶标。

 

Ø  HBV基因突变与肝癌相关性研究及肝癌预警模型的建立

首次系统研究了江苏启东肝癌高发区HBV DNA异质性与肝癌的关系,确认了肝癌相关性HBV突变可作为新的肝癌预警和诊断标志物(J Hepatol, 2008, 49:718Arch Virol, 2008, 153:1807Cancer Epidemiol Biomarkers Prev, 2010, 19:2623Carcinogenesis, 2011, 32:63Intervirology, 2012, 55:29; PLoS One. 2014, 9:e94864)。以病毒和宿主参数共同构建的肝癌预警评分系统,有望在国内肝癌筛查中发挥积极作用。

20161007090480478047.png

 

Development and application of Qidong Hepatocellular Carcinoma (HCC)

(A) Development of HCC Prediction System (HCC Predictor). (B) HCC cumulative incidence probabilities in different groups divided by HCC Predictor.

 

Ø  HBV 感染与肝外肿瘤

实验室研究发现,胰腺癌和恶性淋巴瘤患者中HBV慢性感染率显著高于正常人群,在胰腺癌和恶性淋巴瘤组织中存在着的HBV感染和整合的证据(Cancer Lett. 2013, 28;335:447)。我们将通过进一步的体内外实验,深入探讨HBV感染在胰腺癌、淋巴瘤中的作用和机制,为上述恶性肿瘤的防控提供新思路。

 

II 肿瘤的系统性调控

肿瘤是一种系统性疾病。癌虽然表现为局部组织细胞的异常生长,但人体神经、免疫和内分泌等系统对其发生发展起着重要的调控作用。我们已发现将小鼠饲养在丰富生存环境中(良性心理应激),能显著抑制胰腺癌、结肠癌、乳腺癌、黑色素瘤等恶性肿瘤的生长,这一作用可能与肿瘤细胞线粒体能量代谢改变有关(Sci Rep. 2015, 5:7856)。我们还发现丰富生存环境对肿瘤化疗具有增敏作用(Biochem Biophys Res Commun. 2016, 473:593)。在此基础上,我们进一步研究发现精神心理行为通过交感神经调控NK细胞抗肿瘤免疫活性,从而发挥抑瘤作用。

20161007090555945594.png

 

Anti-tumor effect induced by enriched environment (EE) exposure

(A) EE reduces tumor growth in various mouse tumor models. (B) EE enhances the anti-tumor effect of chemotherapeutic drugs. (C) Schematic illustrating potential pathways of enhanced NK-mediated anti-tumor immunity induced by EE exposure.


近五年代表性文章

 

 

 

1. Wu Y, Gan Y, Yuan H, Wang Q, Fan Y, Li G, Zhang J, Yao M, Gu J, Tu H. Enriched environment housing enhances the sensitivity of mouse pancreatic cancer to chemotherapeutic agents. Biochem Biophys Res Commun. 2016 473(2):593-9.

2. Fan Y, Gan Y, Shen Y, Cai X, Song Y, Zhao F, Yao M, Gu J, Tu H. Leptin signaling enhances cell invasion and promotes the metastasis of human pancreatic cancer via increasing MMP-13 production. Oncotarget. 2015 6(18): 16120-34.

3. Li G, Gan Y, Fan Y, Wu Y, Lin H, Song Y, Cai X, Yu X, Pan W, Yao M, Gu J, Tu H. Enriched environment inhibits mouse pancreatic cancer growth and down-regulates the expression of mitochondria-related genes in cancer cells. Sci Rep. 2015, 5:7856.

4. Zhao ZM, Jin Y, Gan Y, Zhu Y, Chen TY, Wang JB, Sun Y, Cao ZG, Qian GS, Tu H. Novel approach to identifying the hepatitis B virus pre-S deletions associated with hepatocellular carcinoma. World J Gastroenterol. 2014, 20:13573-81.

5. Wu S, Liu J, Wang X, Li M, Gan Y, Tang Y. Association of obesity and overweight with overall survival in colorectal cancer patients: a meta-analysis of 29 studies. Cancer Causes Control. 2014, 25:1489-502.

6. Wu Y, Gan Y, Gao F, Zhao Z, Jin Y, Zhu Y, Sun Z, Wu H, Chen T, Wang J, Sun Y, Fan C, Xiang Y, Qian G, Groopman JD, Gu J, Tu H. Novel natural mutations in the hepatitis B virus reverse transcriptase domain associated with hepatocellular carcinoma. PLoS One. 2014, 9:e94864

7. Cai X, Gan Y, Fan Y, Hu J, Jin Y, Chen F, Chen T, Sun Y, Wang J, Qin W, Tu H. The adiponectin gene single-nucleotide polymorphism rs1501299 is associated with hepatocellular carcinoma risk. Clin Transl Oncol. 2013 16:166-72.

8. Wu S, Gan Y, Wang X, Liu J, Tang Y. PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis. J Cancer Res Clin Oncol. 2013 139:891-900.

9. Yan Jin, Hengjun Gao, Hao Chen, Jian Wang, Min Chen, Guohua Li, Liwei Wang, Jianren Gu, Hong Tu. Identification and impact of hepatitis B virus DNA and antigens in pancreatic cancer tissues and adjacent non-cancerous tissues. Cancer Lett. 2013, 28;335:447-54.

10. Chen M, Li G, Yan J, Lu X, Cui J, Ni Z, Cheng W, Qian G, Zhang J, Tu H. Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma. Clin Chim Acta. 2013, 23;423:105-11

11. Zhu Y, Jin Y, Cai X, Bai X, Chen M, Chen T, Wang J, Qian G, Gu J, Li J, Tu H.  Mutation pattern of hepatitis B virus core protein derived from hepatocellular carcinoma. Intervirology, 2012;55:29-35.

12. Bai X, Zhu Y, Jin Y, Guo X, Qian G, Chen T, Zhang J, Wang J, Groopman JD, Gu J, Tu H. Temporal acquisition of sequential mutations in the enhancer II and basal core promoter of HBV in individuals at high-risk for hepatocellular carcinoma  Carcinogenesis, 2011, 32:63-8.