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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年吴虹教授入选国家级人才计划并于同年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。吴虹课题组研究重点是结合肿瘤分子遗传学,基因组学,生物信息学及肿瘤模型,揭示癌症发生、发展及耐药的机制,寻找更有效的癌症靶向治疗、免疫治疗方法。主要的研究方向包括:
1. PTEN调控干细胞和肿瘤干细胞的分子遗传机制;
2. 前列腺癌单细胞图谱及癌细胞与肿瘤微环境的互作网络绘制;
3. 天然免疫及细胞坏死在前列腺癌进展中的作用机制;
4. 肿瘤发生过程中的代谢重编程。
1. Zhu, Haichuan; Dong, Bingjie; Zhang, Yingchi; Wang, Mei; Rao, Jianan; Cui, Bowen; Liu, Yu; Jiang, Qian; Wang, Weitao; Yang, Lu; Yu, Anqi; Li, Zongru; Liu, Chao; Zhang, Leping; Huang, Xiaojun; Zhu, Xiaofan; Wu, Hong. Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia. Blood Science 4, 16-28, doi:10.1097/bs9.0000000000000102 (2022).
2. Xue, Yue; Yang, Ying; Tian, Tao, Quan, Hui; Liu, Sirui; Zhang, Ling; Yang, Lu; Zhu, Haichuan; Wu, Hong; Gao, Yiqin. Computational characterization of domain-segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis. Mol Oncol 16, 699-716, doi:10.1002/1878-0261.13127 (2022).
3. Zhi, Q., Xu, Z., Zhang, L., Zou, Y., Li, J., Yan, W., Li, C., Liu, N. and Wu, H. Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment. Nat Commun. 2022 Jan 10;13(1):182. PMID: 35013322
4. Yang, L., Chen, F., Zhu, H., Chen, Y., Dong, B., Shi, M., Wang, W., Jiang, Q., Zhang, L., Huang, X., Zhang, M., Wu, H. (2021) 3D Genome Alterations Associated with Dysregulated HOXA13 Expression in High-Risk T-Lineage Acute Lymphoblastic Leukemia. Nat Commun. 2021 Jun 17;12(1):3708. PMID: 34140506
5. 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. Nat Commun. 20;11(1):1880. PMID: 32312982
6. Wu, Y., Zhu, H., and Wu, H. (2019). PTEN in Regulating Hematopoiesis and Leukemogenesis. Cold Spring Harb Perspect Med. PMID:31712222.
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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.
1. 11. 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
13. 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
14. 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
15. 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.
16. 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.
17. 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
2. 17. 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
3. 18. 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
4. 19. 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
5. 20. 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
6. 21. 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
7. 22. 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.
8. 23. 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
9. 24. 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
10. 25. 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
11. 26. 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
12. 27. 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
13. 28. 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
14. 29. 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
15. 30. 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
16. 31. 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
17. 32. 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
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21. 36. 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
22. 37. 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
23. 38. Chang, C., Mulholland, D., Valamehr, B., Mosessian, S., Sellers, W. andWu, H. (2008) PTEN Nuclear Localization Is Regulated by Oxidative Stress and Responsible for p53-Dependent Tumor Suppression. Mol. Cell. Biol. 28:3281-9. PMCID: PMC2423144
24. 39. 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
25. 40. 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
26. 41. 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
27. 42. 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
28. 43. 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
29. 44. 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
30. 45. 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
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34. 49. Stiles, B., Kurlawalla-Martinez, C., Guo, W., Gregorian, C., Wang, Y., Tian, J. Magnuson, M.A. and Wu, H. (2006) Selective deletion of Pten in pancreatic -cells leads to increased  cell mass and resistance to STZ-induced diabetes. Mol. Cell Biol. 26:2772-81. PMCID: PMC1430339
35. 50. 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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48. 63. Wong, K., Kim, R., Christofk, H., Gao, J. and Wu, H. (2004) Protein inhibitor of activated STAT Y (PIASy) enhances sumoylation but is not essential for embryogenesis and adult life. Mol. Cell Biol. 12:5577-5586. PMCID: PMC419860
49. 64. Stiles, B., Wang, Y., Stahl, A., Bassilian, S., Lee, W.P., Kim, Y-J., Sherwin R., Devaskar, S., Lesche, R., Magnuson, M., and Wu, H. (2004) Live-Specific Deletion of negative regulator Pten Results in Fatty Liver and Insulin Hypersensitivity. Proc. Natl. Acad. Sci. USA101: 2082-2087. PMCID: PMC357055
50. 65. Wang, S., Gao, J., Lei, Q-Y., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G., Li, G., Roy-Burman, P., Nelson, P., Liu, X., and Wu, H. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4:209-221.PMID: 14522255
51. 66. 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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