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吴虹

邮  箱: hongwu@pku.edu.cn

职  称:教授

实验室电话:62765646

实验室地址:北京市海淀区颐和园路5号,北京大学,吕志和楼,100871

  • 个人简介
  • 科研领域
  • 代表性论文
  • 实验室简介

教育经历:

1984 - 1991 , 博士 , 哈佛医学院
1978 - 1983 , 学士 , 北京医学院

工作经历:

2013 - 至今 , 院长 , 北京大学生命科学学院
2011 - 2013 , 主任 , 美国加州大学洛杉矶分校分子医学研究所  
2009 - 至今 , David Geffen Chair in Medical Research , 美国加州大学洛杉矶分校
2008 - 2011 , 副主任 正式成员 , 美国加州大学洛杉矶分校分子医学研究所
1997 - 2004 , 助理研究员 , 霍华德-休斯医学研究所
1996 - 2013 , 助理教授、副教授、教授 , 美国加州大学洛杉矶分校分子与医学药理学系
1991 - 1996 , 博士后 , 麻省理工学院Whitehead研究所
          吴虹教授长期致力于肿瘤分子遗传学的研究,重点探讨抑癌基因在肿瘤发生、发展及耐药中的分子机制。她所领导的团队在抑癌基因信号传递、肿瘤干细胞及基因工程动物模型等研究方面做了大量的杰出工作,其研究成果对于发现肿瘤发生的分子机制以及肿瘤治疗的新途径有重大的理论及实际意义。截至2018年3月,吴虹教授发表SCI收录科学论文160余篇,引用2万余次。基于她在肿瘤分子遗传学领域的重大贡献及卓越成就,曾获得皮尤学者(Pew Scholar)、霍华德休斯助理研究员(HHMI Assistant Investigator)等多项奖励和荣誉,并于2010年当选为美国科学促进会会士(Fellow of American Association for the Advancement of Science),2016年当选为欧洲分子生物学组织(European Molecular Biology Organization, EMBO)外籍院士。
    2013年吴虹全职回国任北京大学生命科学学院讲席教授、北京大学生命科学学院院长,同时任北京大学-清华大学生命科学联合中心研究员、北京大学北京未来基因诊断高精尖创新中心研究员。吴虹课题组目前的主要研究方向为通过建立的PTEN缺失相关的多种肿瘤模型,应用分子遗传学、蛋白质组学、高通量测序、单细胞测序等手段研究PTEN信号通路与肿瘤发生发展的关系、筛选靶向药物、揭示肿瘤耐药机制。目前关心的主要科学问题如下:
    1. PTEN调控干细胞和肿瘤干细胞的分子遗传机制;
    2. PI3K与其他信号通路的相互作用在肿瘤发生、转移和耐药中的功能;
    3. 中国人群前列腺癌和T细胞急性淋巴细胞白血病基因组图谱
1. Cheng. J., Huang. Y., Zhang. X, Yu. Y., Wu. S., Jiao J., Tran. L., Zhang, W., Liu. R., Zhang, L., Wang. M., Wang, M., Yan, W., Wu, Y., Chi, F., Jiang. P., Zhang. X., and Wu, H.(2020) TRIM21 and PHLDA3 Negatively Regulate the Crosstalk between the PI3K/AKT Pathway and PPP Metabolism. Nature Communication. In press.
2. Wu, Y., Zhu, H., and Wu, H. (2019). PTEN in Regulating Hematopoiesis and Leukemogenesis. Cold Spring Harb Perspect Med. PMID:31712222.
3. Zhu, H., Zhang, L., Wu, Y., Dong, B., Guo, W., Wang, M., Yang, L., Fan, X., Tang, Y., Liu, N., Lei X., and Wu H. (2018). T-ALL leukemia stem cell 'stemness' is epigenetically controlled by the master regulator SPI1. Elife 7. PMID: 30412053
4. Zou, Y., Qi, Z., Guo, W., Zhang, L., Ruscetti, M., Shenoy, T., Liu, N., and Wu, H. (2018). Cotargeting the Cell-Intrinsic and Microenvironment Pathways of Prostate Cancer by PI3Kalpha/beta/delta Inhibitor BAY1082439. Mol Cancer Ther 17, 2091-2099. PMID: 30045927
5. Shenoy, T.R., Boysen, G., Wang, M.Y., Xu, Q.Z., Guo, W.L., Koh, F.M., Wang, C., Zhang, L.Z., Wang, Y., Gil, V., Aziz, S., Christova, R., Rodrigues, D.N., Crespo, M., Rescigno, P., Tunariu, N., Riisnaes, R., Zafeiriou, Z., Flohr, P., Yuan, W., Knight, E., Swain, A., Ramalho-Santos, M., Xu, D.Y., de Bono, J. and Wu, H. (2017) CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair. Ann Oncol. Jul 1;28(7):1495-1507.PMID: 28383660
6. Schubbert S., Jiao, J., Ruscetti, M., Nakashima, J., Wu, S., Lei, H., Xu, Q., Yi, W., Zhu, H., Wu, H. (2016) Methods for PTEN in Stem Cells and Cancer Stem Cells Methods Mol. Biol. 1288:233-85. PMID:27033080
7. Ruscetti, M., Dadashian, E.L., Guo, W., Quach, B., Mulholland D.J., Park J.W., Tran, L.M., Kobayashi, N., Bianchi-Frias, D., Nelson, P.S., Xing, Y. and Wu, H. (2016) HDAC Inhibition Impedes Epithelial-Mesenchymal Plasticity and Suppresses Metastatic, Castration-Resistant Prostate Cancer. Oncogene. 2016.7.21, 35(29): 3781~3795 PMID:26640144
8. Ruscetti, M., Quach, B., Dadashian, E.L., Mulholland, D.J. and Wu, H. (2015) Tracking and functional characterization of EMT and mesenchymal-like tumor cells in prostate cancer metastasis. Cancer Res. 75:2749-59. PMCID:PMC4490048.
9. 7. Schubbert S, Cardenas A, Chen H, Garcia C, Guo W, Bradner JE, Wu H.  Targeting the MYC and PI3K pathways eliminates leukemia-initiating cells in T cell acute lymphoblastic leukemia. (2014) Cancer Res74:7048-59.PMCID:PMC4258248
10. Pulido R, Baker SJ, Barata JT, Carracedo A, Cid VJ, Chin-Sang ID, Davé V, den Hertog J, Devreotes P, Eickholt BJ, Eng C, Furnari FB, Georgescu MM, Gericke A, Hopkins B, Jiang X, Lee SR, Lösche M, Malaney P, Matias-Guiu X, Molina M, Pandolfi PP, Parsons R, Pinton P, Rivas C, Rocha RM, Rodríguez MS, Ross AH, Serrano M, Stambolic V, Stiles B, Suzuki A, Tan SS, Tonks NK, Trotman LC, Wolff N, Woscholski R, Wu H, Leslie NR. (2014) A Uniform Nomenclature and Amino Acid Numbering for Human PTEN. Science Signal. 7: pe15PMCID:PMC4367864
11. Garcia, A.J., Ruscetti, M., Arenzana, T.L., Tran, L.M., Frias D.B., Sybert, E., Priceman, S.J., Wu, L., Nelson, P., Smale, S and Wu, H. (2014) Pten null prostate epithelium promotes localized MDSC expansion and immune suppression during tumor initiation and progression. Mol Cell Biol. 34:2017-2028. PMCID:PMC4019050
12. Ruscetti, M and Wu, H. (2013) PTEN in Prostate Cancer. In Prostate Cancer: Biochemistry, Molecular Biology, Genetics and Protein Reviews. Don J. Tindall (editor). Mayo Clinic (in press).
13. Mulholland, D., and Wu, H. (2013) A Book Chapter in “Stem Cells and Prostate Cancer”; Chapter 5 – Genetic and Signaling Pathway Regulations Springer Science-Business Media 77-89.
14. Smith, K.B., Tran, L.M., Tam, B.,Shurell, E.M., Li, Y., Braas, D., Tap, W.D., Christofk, H.R., Dry, S.M., Eiber, F.C., and Wu, H. (2013) Novel dedifferentiated liposarcoma xenograft models reveal PTEN down regulation as a malignant Signature and Response to PI3K Pathway Inhibition. American Journal of Pathology 182(4):1400-11. PMCID: PMC3620414.
15. Schlacher, K., Wu, H., and Jasin, M. (2012) A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1/2. Cancer Cell 22(1):106-16. PMID: 22789542
16. 14. Hubner, A., Mulholland, D., Standen, C., Karasarides, M., Cavanagh-Kyros, J., Barrett, T., Chi, H., Greiner, D., Tournier, C.,  Flavell, R., Sawyers, C., Wu H., and Davis, R. (2012) JNK and PTEN co-operatively control the development of invasive adenocarcinoma of the prostate. Proc. Natl. Acad. Sci. USA109(30):12046-51. PMCID: PMC3409732
17. Mulholland, D., Kobayashi, N., Ruscetti, M., Zhi, A., Tran, L.M., Huang, J., Gleave, M and Wu, H (2012) Pten loss and RAS/MAPK activation coorperate to promote EMT and prostate cancer metastasis initiated from stem/progenitor cells. Cancer Res.72 (7):1878-89. PMCID: PMC3319847
18. Tran, L.M., Chang, C., Plaisier, S., Dang, J., Mischel, P.S., Liao, J., Graeber, T.G. and Wu, H. (2012) Determining PTEN functional status by network component deducted transcription factor activities. PLoS One 7(2):e31053. PMCID: PMC 3275574
19. Donahue, T.R., Tran, M.L., Hill, R., Li, Y, Kovochich, A., Calvopina, J., Patel, S.G., Farrell, J.J., Li, X., Dawson, D. and Wu, H. (2012) Integrative survival-based molecular profiling of Human Pancreatic Cancer. Clinic Cancer Res.18(5): 1352-63. PMID: 22261810
20. Valamehr, B., Tsutsui, H., Ho, C.M., and Wu, H (2011) Developing defined culture system for human pluripotent stem cells. Regen. Med. 6:623-634. PMID: 21916597
21. Mulholland, D., Tran, M.L., Cai, H., Morim, A., Wang, S., Plaisier, S., Huang, J., Garraway, I., Graeber, T. and Wu, H. (2011) Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell 19, 792-804. PMCID:PMC3157296.
22. Schlacher, K., Christ, N., Siaud, N., Egashira, A., Wu, H. and Jasin, M. (2011) Homologous recombination independent role for BRCA1 in blocking stalled replication folk degradation by MRE11. Cell145, 529-542. PMCID: PMC3261725
23. Le Belle, J., Orozco, N.M., Paucar, A., Saxe, J., Mottahedeh, J., Pyle, A., Wu, H. and Kornblum, H. (2011) Proliferative neural stem cell maintain high endogenous levels of reactive oxygen species that regulate self-renewal and neurogenesis in a PI3K/AKT-dependent manner. Cell Stem Cell 8 (1): 59-71.PMCID: PMC3018289
24. Guo, W., Schubbert, S., Chen, J-Y, Valamehr, V., Mosessian, S., Shi, H., Garcia, C., Theodoro, M.F., Varella-Garcia, M and Wu, H. (2011) Suppression of leukemia and leukemia stem cell transformation. Proc. Natl. Acad. Sci. USA 108, 1409-14.PMCID: PMC3029702
25. Lukacs, R., Memarzadeh, S., Wu, H. and Witte, O (2010) Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation. Cell Stem Cell 7(6):682-93. PMCID: PMC3019762
26. Tsutsui, H., Valamehr, B., Hindoyan, A., Qiao, R., Ding, X., Guo, S., Witte, O., Liu, X., Ho, C.M., and Wu, H. (2011) An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells. Nature Communications 2:167. PMCID: PMC3161511
27. Hill, R., Calvopina, J.H., Kim, C., Wang, Y., Dawson, D.W., Donahue, T.R., Dry, S., Wu, H. (2010) PTEN Loss Accelerates KrasG12D-Induced Pancreatic Cancer Development. Cancer Res 70 (18):7114-24.PMCID: PMC2940963
28. 26. Gregorian, G., Nakashima, J., Dry, S.M., Nghiemphu, P.L., Smith, K.B., Ao, Y., Dang, J., Lawson, G., Mellinghoff, I.K., Mischel, P.S., Phelps, M., Parada, L., Liu, X., Sofroniew, M.V., Eilber, F.C. and Wu, H. (2009) PTEN Dosage is Essential for Neurofibroma Development and Malignant Transformation.  Proc. Natl. Acad. Sci. USA 106: 19479-84. PMCID: PMC2765459
29. Mosessian, S., Avliyakulov, N.K., Mulholland, D.J., Boontheung, P., Loo, J.A. and Wu, H. (2009) Analysis of PTEN Complex Assembly and Identification of Heterogeneous Nuclear Ribonucleoprotein C as a Component of the PTEN-associated Complex. J. Biol. Chem 284: 30159-66. PMCID: PMC2781571
30. Mulholland, D.J., Xin, L., Morim, A., Lawson, D., Witte, O., and Wu, H (2009)Lin-Sca-1+CD49high stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model. Cancer Res 69:8555-8562. PMCID: PMC2783355
31. 29. Guertin, D.A., Stevens, D.M., Saitoh, M., Crosby, K., Cormier, K.S., Mulholland, D.J., Magnuson, M.A., Wu, H., Sabatini, D.M. (2009) The mTOR complex 2 is required for the development of prostate cancer induced by PTEN loss in mice.  Cancer Cell 15:148-59. PMCID: PMC2701381
32. Gregorian, C., Nakashima, J., Ohab, J., Kim, R., Liu, A., Groszer, M., Garcia, D., Sofroniew, M., Carmichael, T., Liu, X. and Wu, H. (2009) Pten Deletion in Adult Neural Stem/Progenitor Cells Enhances Constitutive Neurogenesis. J. Neuroscience 29: 1874-86. PMCID: PMC2754186
33. Valamehr, B., Jonas, S., Polleux, J., Kam, K, Qiao, R., Stiles, B., Luo, T., Witte, O., Liu, X., Dunn, B. and Wu, H. (2008) Hydrophobic Surfaces for Enhanced Differentiation of Embryonic Stem Cells. Proc. Natl. Acad. Sci. USA 105:14459-64.PMCID: PMC2567159
34. Burton JB, Johnson M, Sato M, Koh SB, Stout S, Mulholland D, Chatziioannou AF, Phelps M, Wu H. and Wu L. (2008) Adenovirus Mediated Gene Expression Imaging to Directly Detect Sentinel Lymph Node Metastasis of Prostate Cancer. Nature Med.14:882-9. PMCID: PMC2811163
35. Kwon, C.H., Zhao, D., Chen, J., Alcantara, S., Li, Y., Burns, D., Mason, R.P., Lee, E.Y-H., Wu, H and Parada, L. (2008) Ptenhaploinsufficiency accelerates formation of high grade astrocytomas. Cancer Res. 68:3286-94. PMCID: PMC2760841
36. Mulholland, D.J., Jiao, J. and Wu, H (2008) Hormone refractory prostate cancer: lesions leaned from the PTEN prostate cancer model. Adv Exp Med Biol 617:87-95. PMID:18497033
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38. Guo, W., Lasky, J, Chang, C., Mosessian, S., Lewis, X., Xiao, Y., Yeh, J., Chen, J., Iruela-Arispe, L., Varella-Garcia, M. and Wu, H. (2008) Multi-genetic events collaboratively to Pten-null leukaemia stem-cell formation. Nature 453: 529-533.PMCID: PMC2840044
39. Tahk S., Liu, B., Chenishof, V., Wong, K., Wu, H. and Shuai, K (2007) Control of specificity and magnitude of NF-kB and STAT1-mediated gene activation through PIASy and PIAS1 co-operation. Proc. Natl. Acad. Sci. USA 104: 11643-11648. PMCID: PMC1913887
40. Jiao, J., Wang, S., Qiao, R., Vivanco, I., Watson, P., Sawyers, C. and Wu, H. (2007) Murine Cell Lines Derived from Pten Null Prostate Cancer Demonstrate the Critical Role of PTEN in Hormone Refractory Prostate Cancer Development. Cancer Res 67: 6083-91. PMID: 17616663
41. Vivanco, I., Palaskas, N., Tran, C., Finn, S.P., Getz, G., Kennedy, N.G., Jiao, J., Rose, J., Xie, W., Loda, M., Golub, T., Mellinghoff, I., Davis, R., Wu, H. and Sawyers, C.L (2007) Identification of the JNK Signaling Pathway as a Functional Target of the Tumor Suppressor PTEN. Cancer Cell 11: 555-569. PMID:17560336
42. He, X., Zhang, J., Grindley, J.C., Tian, Q., Sato, T., Tao, W.A., Dirisina, R., Porter-Westpfahl, K.S., Hembree, M., Johnson, T., Wiedemann, L., Barrett, T., Hood, L., Wu, H. and Li, L. (2007) Inactivation of PTEN leads to enhanced activation of intestinal stem cells and biasing on lineage fate determination. Nature Genetics 39: 189-98. PMID: 17237784
43. Freeman, D., Lesche, R., Kertesz, N., Wang, S-Y., Li, G., Gao, J., Groszer, M., Martinez-Diaz, H., Rozengurt, N., Thomas, G., Liu, X., and Wu, H. (2006) Genetic Background Controls Tumor Development in Pten Deficient Mice. Cancer Res 66: 6492-6496. PMID:16818619
44. Zhang, J., Grindley, J., Yin, T., Jayainghe, S., He, X., Ross, J., Haug, J., Rupp, D., Porter-Westpfahl, K., Wiedemann, L., Wu, H., and Li, L (2006) An essential role of PTEN in hematopoietic stem cell maintenance, lineage choice, and leukemia prevention. Nature 441: 518-522. PMID: 16633340
45. Lei, Q., Jiao, J., Xin, L., Chang, C., Wang, S., Gao, J., Gleave, M.E., Witte, O., Liu, X. and Wu, H. (2006) NKX3.1 stabilizes p53, inhibits AKT activation and delays prostate cancer initiation caused by PTEN loss. Cancer Cell 9: 367-78. PMID:16697957
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49. Tsai, P., Ohab, J., Kertesz, N., Groszer, M., MatterC, Gao, J., Liu, X., Wu, H. and Carmichael, S.T. (2006) A Critical Role of Erythropoietin Receptor in Neurogenesis and post-stroke recovery. J. Neurosciences 26:126901274. PMID:16436614
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65. Tsai, P., Lee, R.A., and Wu, H., (2003) BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Blood 102:3947-3953. PMID:12920023
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67. Anzelon, A., Wu, H., and Rickert R. (2003) Pten Inactivation Alters Peripheral B Lymphocyte Fate and Reconstitutes CD19 Function. Nature Immunology 4:287-294. PMID:12563260
68. Freeman, D., Wei, G., Li, H., Li, A., Lesche, R., Whale, A., Martinez-Diaz, H., Rozengurt, N., Liu, X. and Wu, H. (2003) PTEN Tumor Suppressor Gene Regulates p53 Through Both MDM2-Dependent and Independent Mechanisms. Cancer Cell 3:117-129.
69. Li, G., Robinson, G.W., Lesche, R., Martinez-Diaz, H., Jiang, Z.R., Rozengurt, N., Wagner, K., Wu, D.C., Lane, T.F., Liu, X., Hennighausen, L., and Wu, H. (2002) Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129:4159-4170. PMID:12163417
70. Stiles, B., Gilman, V., Khnzenzon, N., Lesche, R., Li, A., Qiao, R., Liu, X., and Wu, H. (2002) The Essential Role of AKT-1/PKB in PTEN Controlled Tumorigenesis. Mol. Cell. Biology 22: 3842-3851. PMCID: PMC133830
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