吴文书博士是海南医科大学衰老与肿瘤国际研究中心（ICAC）特聘教授，硕士/博士及博士后导师，科技部特聘专家。回国全职加盟 ICAC 之前，曾任美国伊利诺伊大学芝加哥分校医学系终身教授，此前还在缅因医学中心研究所、塔夫茨大学医学院、加州大学旧金山分校贝尼奥夫儿童医院、加州大学伯克利分校干细胞中心等机构担任全职或兼职教职并任项目负责人（PI）。研究长期聚焦胚胎干细胞、血液干细胞、白血病、肌肉干细胞与衰老等前沿方向，在            Cell、Blood、J Clin Invest、Nat Commun、Molecular Cancer、Leukemia、Molecular Therapy、Stem Cell Reports、Cell Research、Oncogene 等期刊发表多篇高水平论文。

其工作首次揭示了放射线对人体造血系统造成损伤的细胞和分子机制，该成果曾被 Cell 选为封面文章，引起广泛关注。主持多项 NIH 等机构资助的科研项目，多次受邀参加 NIH、英国 MRC、以色列科技基金会的项目评审；担任 Genes & Diseases 编委，以及 Frontiers in Molecular and Cellular Pathology、Scientific Reports 等期刊的审稿编辑。

1983.09–1987.07  华东师范大学 生命科学学院 生物学  — 学士

1987.09–1990.07  上海交通大学医学院（原上海第二医科大学） 免疫学  — 硕士

1997.09–2001.12  美国德克萨斯大学 MD Anderson 癌症中心  癌症生物学  — 博士

2001.12–2005.01  哈佛大学 Dana–Farber 癌症研究所 博士后

吴博士长期从事干细胞生物学、衰老、肿瘤发生机制与基因编辑的基础与转化研究，实验室已建立多种小鼠疾病模型，掌握血液和肌肉干细胞分离培养、分子生物学及体内基因递送等一系列关键技术；并在学生培养方面经验丰富，多名博士后已在中美高校和科研机构获得教职或管理岗位。

• 干细胞生物学

• 衰老分子机制

• 癌症治疗与转化

1. 肌肉干细胞 Galert（激活预警态）细胞周期的调控与机制

2. Snail / Slug 基因家族调控衰老的分子机制

3. 抗衰老分子及其信号通路的发现与作用机制解析

4. 造血干细胞（HSC）自我更新的分子机制及体内 HSC 靶向基因递送技术研发

5. 骨髓增生性肿瘤的基因编辑治疗策略

1. Yanwen Ge, Mei Hong, Yu Zhang, Jiachen Wang, Lei Li, Hongkai Zhu, Yue Sheng, Wen-Shu Wu*, Zhonghui Zhang*. miR-30e-5p regulates leukemia stem cell self-renewal through the Cyb561/ROS signaling pathway. Haematologica, 2024 Feb 1;109(2):411-421.

2. Min-Hyun Kim, Yuan Li, Qiantao Zheng, Lin Jiang, Martin G. Myers Jr., Wen-Shu Wu, Liangyou Rui. LepRb⁺ cell–specific deletion of Slug mitigates obesity and nonalcoholic fatty liver disease in mice. J Clin Invest. 2023;133(4):e156722. doi:10.1172/JCI156722.

3. Yan Liu, Haiyan Lin, Lin Jiang, Qingsen Shang, Lei Yin, Jiandie D. Lin, Wen-Shu Wu*, Liangyou Rui*. Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes. J Clin Invest. 2020 Jun 1;130(6):2992-3004. doi:10.1172/JCI128073.

4. Zhonghui Zhang, Lei Li, Chen Wu, Guoshu Yin, Pei Zhu, Yalu Zhou, Yuanfan Hong, Hongyu Ni, Zhijian Qian, Wen-Shu Wu*. Inhibition of Slug effectively targets leukemia stem cells via the Slc13a3/ROS signaling pathway. Leukemia, 2020 Feb;34(2):380-390.

5. Pei Zhu, Chunping Zhang, Yongxing Gao, Furen Wu, Yalu Zhou, Wen-Shu Wu*. The transcription factor Slug represses p16^Ink4a and regulates murine muscle stem cell aging. Nat Commun. 2019;10(1):2568.

6. Pei Zhu, Furen Wu, Jeffrey Mosenson, Hongmei Zhang, Tong-Chuan He, Wen-Shu Wu*. CRISPR/Cas9-mediated genome editing corrects dystrophin mutation in skeletal muscle stem cells in a mouse model of muscle dystrophy. Mol Ther-Nucleic Acids, 2017 Jun 16;7:31-41.

7. Pei Zhu, Yalu Zhou, Furen Wu, Yuanfan Hong, Xin Wang, Gajendra Shekhawat, Jeffrey Mosenson, Wen-Shu Wu*. Selective expansion of skeletal muscle stem cells from bulk muscle cells in soft 3D fibrin gel. Stem Cell Transl Med. 2017 May;6(5):1412-1423.

8. Zhonghui Zhang, Pei Zhu, Yalu Zhou, Yue Sheng, Yuanfan Hong, Di Xiang, Zhijian Qian, J. Mosenson, Wen-Shu Wu*. A novel Slug-containing negative feedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal. Leukemia, 2017 Feb;31(2):403-413.

9. Fidalgo M., Huang X., Guallar D., Sanchez-Priego C., Valdes V. J., Saunders A., Ding J., Wen-Shu Wu, Clavel C., Wang J. Zfp281 coordinates opposing functions of Tet1 and Tet2 in pluripotent states. Cell Stem Cell, 2016;16:30153-3.

10. Hou Y., Li W., Sheng Y., Li L., Huang Y., Zhang Z., Zhu T., Peace D., Quigley J. G., Wu W., Zhao Y. Y., Qian Z. The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells. Nat Immunol. 2015;16(8):810-818.

11. Berna Uygur, Katrina Abramo, Evgenia Leikina, Calvin Vary, Lucy Liaw, Wen-Shu Wu*. SLUG is a direct transcriptional repressor of PTEN tumor suppressor. Prostate, 2015;75(9):907-916.

12. Zhonghui Zhang, Yuanfan Hong, Di Xiang, Pei Zhu, Elise Wu, Wen Li, Jeffrey Mosenson, Wen-Shu Wu*. MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways. Stem Cell Reports, 2015;4(4):645-657.

13. Zhonghui Zhang, Elise Wu, Zhijian Qian, Wen-Shu Wu*. A multicolor panel of TALE-KRAB-based transcriptional repressor vectors enabling knockdown of multiple gene targets. Scientific Reports, 2014;4(7338):1-7.

14. Zhonghui Zhang, Di Xiang, Francisca Heriyanto, Wen-Shu Wu*. Sodium butyrate upregulates the miR-302/367 cluster by enhancing transactivation of Oct4. Cellular Reprogramming, 2014;16(2):130-139.

15. Zhonghui Zhang, Francisca Heriyanto, Wen-Shu Wu*. Dissecting roles of endogenous microRNA cluster in cellular reprogramming using TALE repressor and TALEN. Stem Cell Reports, 2013;1(3):218-225.

16. Zhonghui Zhang, Wen-Shu Wu*. Sodium butyrate promotes generation of human iPS cells through induction of the miR-302/367 cluster. Stem Cells Dev. 2013;22(16):2268-2277.

17. Stefan Heinrichs, Lily Conover, Carlos E. Bueso-Ramos, Outi Kilpivaara, Ross L. Levine, Kristen Stevenson, Donna Neuberg, Mignon L. Loh, Wen-Shu Wu, Scott J. Rodig, Guillermo Garcia-Manero, Hagop M. Kantarjian, A. Thomas Look. MYBL2 is a hypoinsufficient tumor suppressor gene in myeloid malignancies. eLife, 2013;2:e00825.

18. Ming Ming, Sheng Wang, Wenshu Wu, Vitalyi Senyuk, Michelle M. LeBeau, Giuseppina Nucifora, Zhijian Qian. Activation of Wnt/β-catenin protein signaling induces mitochondria-mediated apoptosis in hematopoietic progenitor cells. J Biol Chem. 2012;287(27):22683-22690.

19. Bai H., Chen K., Gao Y. X., Arzigian M., Xie Y. L., Malcosky C., Yang Y. G., Wu W. S., Wang Z. Z. Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res. 2012;8(1):26-37.

20. Berna Uygur, Wen-Shu Wu*. SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis. Molecular Cancer, 2011;10:139.

21. Zhonghui Zhang, Yongxing Gao, Albert Gordon, Zack Wang, Zhijian Qian, Wen-Shu Wu*. Efficient generation of fully reprogrammed human iPS cells via polycistronic retroviral vector and a new cocktail of chemical compounds. PLoS One, 2011;6(10):e26592.

22. Kang Chen, Hao Bai, Melanie Arzigian, Yong-Xing Gao, Jing Bao, Wen-Shu Wu, Wei-Feng Shen, Zack Wang. Endothelial cells regulate cardiomyocyte development from embryonic stem cells. J Cell Biochem. 2010;111(1):29-39.

23. Jun Liu, Berna Uyger, Zhonghui Zhang, Lijian Shao, Diana Romero, Calvin Vary, Qiang Ding, Wen-Shu Wu*. Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression. Prostate, 2010;70(16):1768-1777.

24. Lijian Shao, Yan Sun, Zhonghui Zhang, Wei Feng, Yongxing Gao, Zailong Cai, Zack Z. Wang, A. Thomas Look, Wen-Shu Wu*. Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood, 2010;115(23):4707-4714.

25. Xu X., Qiao M., Zhang Y., Jing Y., Wei P., Yao J., Gu B., Wang Y., Lu J., Wang Z., Tang Z., Sun Y., Wu W., Shi Q. Quantitative proteomics study of breast cancer cell lines isolated from a single patient: discovery of TIMM17A as a marker for breast cancer. Proteomics, 2010;10(7):1374-1390.

26. Yan Sun, Lijian Shao, Hao Bai, Zack Wang, Wen-Shu Wu*. Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. Blood, 2010;115(9):1709-1717.

27. Bai H., Gao Y., Arzigian M., Wojchowski D., Wu W. S., Wang Z. Z. BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway. J Cell Biochem. 2010;109(2):363-374.

28. Shao L., Wu W. S.* Gene-delivery systems for iPS cell generation. Expert Opin Biol Ther. 2010;10(2):231-242.

29. Lijian Shao, Wei Feng, Yan Sun, Hao Bai, Jun Liu, Caroline Currie, Jaejung Kim, Rafael Gama, Zack Wang, Zhijian Qian, Lucy Liaw, Wen-Shu Wu*. Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame. Cell Research, 2009;19(3):296-306.

30. Liu T. X., Becker M. W., Jelinek J., Wu W. S., Deng M., Mikhalkevich N., Hsu K., Bloomfield C. D., Stone R. M., DeAngelo D. J., et al. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med. 2007;13:78-83.

31. Wen-Shu Wu, Stefan Heinrichs, Dong Xu, Sean P. Garrison, Gerard P. Zambetti, Jerry M. Adams, A. Thomas Look. Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing Puma. Cell, 2005;123:641-653. (Cover: “Slug represses Puma to antagonize apoptosis”, Cell, 2005)

32. Takeshi Inukai, Toshiya Inaba, Jinjun Dang, Ryoko Kuribara, Keiya Ozawa, Atsushi Miyajima, Wen-Shu Wu, A. Thomas Look, Yojiro Arinobu, Hiromi Iwasaki, Koichi Akashi, Keiko Kagami, Kumiko Goi, Kanji Sugita, Shinpei Nakazawa. TEF, an antiapoptotic bZIP transcription factor related to the oncogenic E2A-HLF chimera, inhibits cell growth by down-regulating expression of the common beta chain of cytokine receptors. Blood, 2005;105.

33. Wen-Shu Wu, Zhi-Xiang Xu, Walter N. Hittelman, Paolo Salomoni, Pier Paolo Pandolfi, Kun-Sang Chang. Promyelocytic leukemia protein sensitizes TNF-α-induced apoptosis by inhibiting the NF-κB survival pathway. J Biol Chem. 2003;278:12294-12304.

34. McClain K. L., Laud P., Wen-Shu Wu, Pollack M. S. Langerhans cell histiocytosis patients have HLA-Cw7 and DR4 types associated with specific clinical presentations and no increased frequency in polymorphisms of the TNF-α promoter. Medical and Pediatric Oncology, 2003;41:502-507.

35. Wen-Shu Wu, Zi-Xiang Xu, Rai-qong Ran, Feng Meng, Kun-Sang Chang. Promyelocytic leukemia protein (PML) inhibits Nur77-mediated transactivation through specific functional interaction. Oncogene, 2002;21:3925-3933.

36. Wen-Shu Wu, Zhi-Xiang Xu, Kun-Sang Chang. The promyelocytic leukemia protein represses A20-mediated transcription. J Biol Chem. 2002;27:31734-31739.

37. Akira Inoue, Markus G. Seidel, Wen-Shu Wu, Shintaro Kamizono, Adolfo A. Ferrando, Roderick T. Bronson, Hiromi Iwasaki, Koichi Akashi, Akira Morimoto, Johann K. Hitzler, Tamara I. Pestina, Carl W. Jackson, Ryuhei Tanaka, Miriam J. Chong, Peter J. McKinnon, Takeshi Inukai, Gerard C. Grosveld, A. Thomas Look. Slug, a highly conserved zinc-finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell, 2002;2:279-288.

38. Wen-Shu Wu, Sadeq Vallian, Edward Seto, Wen-Ming Yang, Diane Edmondson, Sharon Roth, Kun-Sang Chang. The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases. Mol Cell Biol. 2001;21:2259-2268.

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