专访Senior研究员赵忱用idea点亮生命

　　

编者按：干细胞与癌症干细胞的信号转导关系一直都是科学家们热衷研究的课题，近期的Nature杂志发表了一篇杜克大学的研究性文章，科学家们找出了维持白血病癌细胞自我复制的信号通路。文章的第一作者是来自中国的高级研究员赵忱博士。

 

4月底的一个早晨，一通越洋电话架设起生物通记者和赵忱博士间的沟通桥梁。

 

在顶级杂志Nature发表文章是快事一件，生物通记者就Nature文章采访了赵忱博士。

 

Hedgehog与白血病癌症干细胞的关联

生物通：请您简单介绍一下Hedgehog信号？您所在的研究小组为何选择Hedgehog作为研究对象？

赵忱：Hedgehog是一个在组织发生，器官发育方面具有重要调控作用的信号通路，同时目前的研究发现，Hedgehog对多种癌症的发生具有重要的作用，比如说，肺癌，胰腺癌。我所在的研究小组主要研究癌症干细胞，由于发现Hedgehog与多种癌症的发生有密切的关系，因此选择Hedgehog作为研究对象。

 

生物通：您所在的研究小组最新的成果发表在Nature杂志上，这表明您和研究小组所做的工作是具有创新性的，简单来说，Hedgehog对CML（慢性骨髓白血病）的干细胞有什么作用，对正常的骨髓干细胞又有什么作用？

 

赵忱：我们的研究发现Hedgehog对正常的骨髓干细胞和CML的骨髓干细胞具有相似的作用，是维持干细胞多能性的重要信号，在正常的干细胞上有一种受体接受Hedgehog信号，维持骨髓干细胞的自我复制能力，如果消除这一受体会导致干细胞失去自我复制能力。同样，Hedgehog对于CML的骨髓干细胞也有类似的作用，我们在动物实验过程中发现抑制CML骨髓干细胞膜上的受体可减缓白血病的发展进程。

 

生物通：Hedgehog可能成为白血病的治疗靶位吗？

赵忱：阻断Hedgehog信号通路有助治疗CML，减缓CML发展，配合其他的治疗药物能有效破坏癌症干细胞的自我维系能力，防止CML复发。目前诺华诺德公司和辉瑞公司都在开发这类药物。

 

生物通：Hedgehog对其他类型的癌症有相似的作用吗？

赵忱：是的，Hedgehog对胰腺癌，成神经管细胞癌，肺癌，脑肿瘤都具有类似的作用，因此具有广泛的应用价值。

 

生物通：实验中研究小组有用哪些实验技术？

赵忱：主要用的还是细胞学方面的一些实验技术，包括用流式细胞仪分离提取干细胞，用逆转录病毒载体阻断Hedgehog信号。

 

生物通：在求学过程中，您在选择实验室方面有什么心得，对于青年学子建立科研思路您有什么建议？

赵忱：从我个人的经历来说吧，以前在国内的时候，我是学医的，主攻病理学。毕业后去了日本读博，开始的时候主要做病理解剖方面的研究，那个时候很少接触细胞实验，后来在日本的老板开始把一些实验给我做，慢慢地我开始对实验感兴趣，毕业后在日本做了2年助教。2004年我申请来到美国，进入Tannishtha Reya的实验室。她主要是做干细胞方面的研究，当时我向她建议，将癌症和血液干细胞联系起来的研究方向会有很大的前景，Tannishtha Reya对此很感兴趣，因此接受我去她的实验室。

 

我觉得选择实验室，一定要选择有课题有科研经费的实验室，同时要有自己的想法，找一个与自己想法吻合的实验室去做博士后。并不是说选择最Top的实验室就好，关键在于找到一个能让自己有所发挥，有所收获的实验室。最Top的实验室竞争的人多，你所付出的必须更多，并且如果和你的专业，和你的idea不符合，那个实验室是不适合你的。因此说，选择实验室要量体裁衣。

 

关键的两点，要有自己的idea，而且实验室的科研课题与你的想法相吻合。

（生物通 张欢）

 

赵忱简介

Education:

Ph.D. Course (1998-2002) Department of Pathology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

 

M.D (1987-1993) China Medical University, 92 North Second Road Shenyang, Liaoning 110001 P.R. China

 

Professional Experience:

Senior Research Associate  (2008-) Department of Pharmacology and Cancer Biology, Duke University Medical Center, LSRC Building, Room C331, Research Drive, Durham, NC 27710

 

Research Associate (Postdoctoral fellow) (2004-2008) Department of Pharmacology and Cancer Biology, Duke University Medical Center, LSRC Building, Room C331, Research Drive, Durham, NC 27710

 

Assistant professor (2002-2004) Department of Microbiology and Immunology, Keio University School of Medicine 35 shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

 

Ph.D. Course (1998-2002) Department of Pathology, Keio University School of Medicine 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

 

Graduate Research Assistant (1996-1998)

Department of Pathology, Keio University School of Medicine 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan

Research Associate (1993-1996)

Department of Pathology, China Medical University, 92 North Second Road, Shenyang, Liaoning 110001, P.R.China

 

Awards and Grants:

Awards

1. Scholarship for Excellent Medical Students, China Medical University (1987-1993)

2. Monbusho Scholarship of Japan (1996-2002)

3. ASBMR Young Investigator Award (2004)

-Cateninb4. Keystone Symposia Scholarship Winner: Wnt and  Signaling in Development and

Disease (2006)

5. Keystone Symposia Scholarship Winner: Stem cells and Cancer (2007)

6. Robert J Fitzgerald Scholar (2008) (Duke, Pharmacology & Cancer Biology)

 

Grants

1. National Natural Science foundation of China (2002, grant number 30200096)

2. Grant-in-Aid for Exploratory Research by the Ministry of Education, Culture, Sports, Science and

Technology, Japan, 2004

3. National Natural Science foundation of China (2006, grant number 30670888)

Articles:

1. Zhao C, Yamada, T, Kuramochi S, Yamazaki, K, Mukai M, Kameyama K, Hata J. Two cases of ectopic hamartomatous thymoma. Virchows Arch. 2000 437:643-647.

 

2. Zhao C, Hashiguchi A, Kondoh K, Du W, Hata J, Yamada T. Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response. Exp Cell Res. 2002 275:200-214.

 

3. Ueno K, Tanaka M, Miyakoshi K, Zhao C, Shinmoto H, Nishimura G, Yoshimura Y. Prenatal diagnosis of atelosteogenesis type I at the 21 week’ gestation. Prenat Diagn. 2002 22:1071-1075.

 

4. Zhao C, Wang EH. Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts. Cellular Signalling 2004 16: 313-321.

5. Sano M, Kikuchi K, Zhao C, Kobayashi M, Nakanishi Y, Nemoto N. Osteoclastogenesis in human breast carcinoma. Virchows Arch. 2004 444: 470-472.

 

6. Matsuo K, Galson DL, Zhao C, Peng L, Laplace C, Wang KZ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem. 2004 279:26475-80.

Matsuo K, Galson DL, Zhao C contributed equally to this work

 

7. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N, Reya T. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nature Immunology. 2005 6:314-322

 

8. Nishiwaki T, Yamaguchi T, Zhao C, Amano H, Kurt DH, Bornstein P, Toyama Y, Matsuo K. Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1. J Bone Miner Res. 2006 21:596-604.

 

9. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Ishikawa H, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metabolism. 2006 4:111-121.

 

10. Wu M, Kwon HY, Rattis F, Blum J, Zhao C, Ashkenazi R, Jackson TL, Gaiano N, Oliver T, Reya T. Imaging hematopoietic precursor division in real-time. Cell Stem Cell. 2007 1:541-554.

 

11. Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM, Lagoo A, -catenin impairs the renewal of normal and CML stem cells inbReya T. Loss of  vivo. Cancer Cell. 2007 12:528-541.

 

12. Congdon KL, Voermans C, Ferguson EC, Dimascio LN, Uqoezwa M, Zhao C, Reya T. Activation of Wnt Signaling in Hematopoietic Regeneration. Stem Cells. 2008 26:1202-1210.

 

13. Kurokawa M, Zhao C, Reya T, Kornbluth S. Inhibition of apoptosome formation by suppression of Hsp90beta phosphorylation in tyrosine kinase-induced leukemias. Mol Cell Biol. 2008 28:5494-5506.

 

14. Wei Q, Zhao Y, Yang ZQ, Dong QZ, Dong XJ, Han Y, Zhao C, Wang EH. Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression. Lung Cancer. 2008 62:181-192.

 

15. Liu Y, Wang Y, Zhang Y, Miao Y, Zhao Y, Zhang PX, Jiang GY, Zhang JY, Han Y, Lin XY, Yang LH, Li QC, Zhao C, Wang EH. Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer. Lung Cancer. 2009 63:375-382.

 

16. Liu Y, Li QC, Miao Y, Xu HT, Dai SD, Wei Q, Dong QZ, Dong XJ, Zhao Y, Zhao C, Wang EH. Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells. Cancer Sci. 2009 100:441-448.

 

17. Liu Y, Dong QZ, Zhao Y, Dong XJ, Miao Y, Dai SD, Yang ZQ, Zhang D, Wang Y, Li QC, Zhao C, Wang EH. P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells. Exp Cell Res. 2009 315:890-898.

 

18. Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, Kwon HY, Kim J, Chute JP, Rizzieri D, Munchhof M, Vanarsdale T, Beachy PA, Reya T. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 2009 458:776-779.

 

 

 

Representative Presentations and Abstracts:

1.Hashiguchi A, Yamada T, Zhao C, Hata J (1998) The functions of Hsp90 in cell cycle control (Japanese). Proceeding 57th Annual Meeting of the Japanese Cancer

Association, pp105, Yokohama.

 

2.Zhao C, Yamada T, Hozumi N, Nakata Y, Hashiguchi A, Du W, Hata J (1999) Establishment of human leukemia invasion models in NOD/SCID mouse (Japanese). Proceeding 58th Annual Meeting of the Japanese Cancer Association, pp618, Hiroshima.

 

3.Zhao C, Yamada T, Hashiguchi A, Hata J (2000) Hsp90 involves in cell growth and associates anti-cancer reagent, doxorubicin. Cold Spring Harbor meeting on molecular chaperones and the heat shock response, pp277.

 

4.Zhao C and Matsuo K (2002) Analysis of osteoclast-specific gene expression in c-Fos-deficient

osteoclast precursors. 1st Wittgenstein Conference: Genetics and Molecular Biology of Skeletal

Development.

 

5.Zhao C, Irie N, Shimoda K, Miyamoto T, Nishiwaki T, Ishikawa H, Suda T and Matsuo K

(2004) Bidirectional signaling by ephrinB2-EphB4 coordinates osteoclast and osteoblast functions to enhance bone formation. 26th ASBMR Annual Meeting, Seattle, USA

 

6. Chen Zhao and Tannishtha Reya (2006) A requirement for beta-catenin in hematopoietic stem cell renewal and maintenance in vivo. Keystone Symposia: Wnt and beta-Catenin Signaling in Development and Disease (E1), Snowbird Resort, Snowbird, Utah