孙宇 - 中国科学院上海营养与健康研究所 -

个人简介

2017- 至今: 中国科学院上海营养与健康研究院研究员 2014-2016年：中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所研究员 2013-2013年：美国VA医学中心，联邦研究员(PI) 2012-2013年：美国University of Washington，研究员、助理教授(均为PI) 2006-2012年：美国Fred Hutchinson Cancer Research Center，博士后、专职研究人员 2005-2006年：加拿大University of British Columbia产科与妇科学系，博士后 2000-2005年：加拿大Dalhousie University生命科学学院，哲学博士 1999-2000年：中国科学院基因组研究所，助理研究员 1996-1999年：中国科学院遗传与发育生物学研究所，理学硕士 1992-1996年：烟台大学生物化学和微生物学系，理学学士

研究领域

肿瘤微环境与临床耐药，细胞衰老和药物靶向（1）肿瘤微环境与临床耐药肿瘤微环境，即肿瘤细胞在体内条件下赖以产生和存活的局部微环境(niche)。这一概念不仅包括了肿瘤细胞本身，更涉及周边的良性基质细胞，后者涵盖了数量众多的成纤维细胞、平滑肌细胞、内皮细胞、免疫和炎性细胞、神经内分泌细胞、胶质细胞、脂肪细胞、周细胞等多种组分，以及它们产生的细胞间质、微血管以及浸润在其中的生物活性分子。早在100多年以前，英国医生Stephen Paget基于乳腺癌的器官特异性转移中的临床观察，就已经提出了著名的“种子与土壤”的概念。然而这一假说在当时并未受到足够的重视，更多的人们将治疗思路仅仅局限于肿瘤细胞本身，导致人类的肿瘤治疗与预防之路走得异常艰难。直到近年，越来越多的科学家开始意识到肿瘤与肿瘤微环境是一个不可分割的整体，而肿瘤于客观上应当被作为一个系统性疾病来思考和研究。肿瘤微环境在理化性质方面与人体正常内环境存在着许多不同，比较显著的是其低氧、低pH以及高压的特点。同时，肿瘤微环境中存在大量的蛋白水解酶、生长因子、细胞因子和趋化因子，可以对肿瘤的增殖、侵袭、粘附、血管生成以及抗癌治疗效率等，造成不可低估的影响，因而如何控制与阻滞微环境来源的这些负面影响，则成为目前医学界集中探索的热点与焦点。（2）细胞衰老和药物靶向细胞是生物体结构和功能的基本单位，而细胞衰老在显微形态上表现为细胞结构的退行性改变，包括细胞变大、轮廓变平、胞核增大、核仁膨胀、核膜凹陷、溶酶体活性上升。细胞衰老在生理学上的表现为功能衰退与代谢紊乱，如细胞周期停滞，细胞复制能力丧失，对促有丝分裂刺激的反应性减弱，对促凋亡因素的反应性下降等。我们实验室近期在胁迫条件下理化因素造成的包括DNA损伤在内的生物大分子破坏导致细胞衰老的发生发展机制上获得一系列进展。其中，胁迫性衰老跟复制性衰老相似，除了呈现以上典型细胞学特征之外，尚表现为长期、慢性和强烈的衰老相关分泌表型(senescence-associated secretory phenotype, SASP)。该表型受到DNA损伤分泌程序(DNA damage secretory phenotype, DDSP)的调控，在核内与胞内多个信号通路组成的高度复杂的信号网络的作用下，最终表现为级联性放大和长期性维持。特别地，老年人群或肿瘤患者在临床条件下的SASP一旦形成，即难以停止或减退，最终在一组关键因子的作用下成为无休循环(not-terminating cycle)。如何通过设计或筛选新型药物、针对SASP或衰老细胞进行积极、精准而高效的靶向干预，控制细胞衰老造成的组织失衡、器官退行性变化等负面影响，是目前临床肿瘤学和老年医学迫切需要解决的关键问题之一。

近期论文

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Zhang, B., Lam, E. and Sun, Y. 2019. Senescent Cells: A New Achilles' Heel to Exploit for Cancer Medicine? Aging Cell. 18(1): e12875. Chen, F., Long, Q., Fu, D.,Zhu, D., Ji, Y., Han, L., Zhang, B., Xu, Q., Liu, B., Li, Y., Wu, S., Yang, C., Qian, M., Xu, J., Liu, S., Cao, L., Chin, Y. E., Lam, E., Coppé, J. P. and Sun, Y. 2018. Targeting SPINK1 in the Damaged Tumour Microenvironment Alleviates Therapeutic Resistance. Nat Commun. 9: 4315. Sun, Y.*,Coppé, J. -P. and Lam, E. W.-F. 2018. Cellular Senescence: the Sought or the Unwanted? Trends Mol Med. pii: S1471-4914(18)30162-X. doi: 10.1016/j.molmed.2018.08.002. Zhang, B., Fu, D., Xu, Q., Wu, C., Cong, X., Zhong, X., Ma, Y., Lv, Z., Chen, F., Han, L., Qian, M., Chin, Y. E., Lam, E. W. -F, Chiao, P. and Sun, Y.* 2018. The Senescence-Associated Secretory Phenotype Is Potentiated by Feedforward Regulatory Mechanisms Involving Zscan4 and TAK1. Nat. Commun. 9: 1723. Zhang, B., Chen, F., Xu, Q., Han, L., Xu, J., Gao, L., Sun, X., Li, Y., Li, Y., Qian, M. and Sun, Y.* 2017. Revisiting ovarian cancer microenvironment: a friend or a foe? Protein Cell. DOI: 10.1007/s13238-017-0466-7. Han, L., Xu, J., Xu, Q., Zhang, B., Lam, E. W. -F. and Sun, Y*. 2017. Extracellular vesicles in the tumor microenvironment: therapeutic resistance, clinical biomarkers and targeting strategies. Med Res Rev. 37(6): 1318-1349. DOI: 10.1002/med.21453. Gomez-Sarosi, L., Sun, Y., Coleman I, Bianchi-Frias D, Nelson PS. 2017. DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes. Mol Cancer Res. 15: 842-851. Sun, Y.* 2016. http://10.20.40.10/wcm/app/editor/editor/images/spacer.gifTumor Microenvironment and Cancer Therapy Resistance. Cancer Lett. 380: 205–215. Xu, Q., Chiao, P. and Sun, Y.* 2016. Amphiregulin in cancer: new insights for translational medicine. Trends Cancer. 2: 111-113. Sun, Y.*, Zhu, D., Chen, F., Qian, M., Wei, H., Chen, W. and Xu, J. 2016. SFRP2 augments WNT16B signaling to promote therapeutic resistance in the damaged tumor microenvironment. Oncogene. 35: 4321-4334. Zhang, B. and Sun, Y.* 2015. http://10.20.40.10/wcm/app/editor/editor/images/spacer.gifhttp://10.20.40.10/wcm/app/editor/editor/images/spacer.gifLandscape and Targeting of the Angpt-Tie System in Current Anticancer Therapy. Transl Med. 5: 157. doi:10.4172/2161-1025.1000157. Laberge, R. M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P. Y., Benz, C. C., Kapahi, P., Nelson, P. S. and Campisi, J. 2015. mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 17: 1049-1061. Chen, F., Zhuang, X., Lin, L., Yu, P., Wang, Y., Shi, Y., Hu, G. and Sun, Y.* 2015. New Horizons in the Tumor Microenvironment Biology: Challenges and Opportunities. BMC Med. 13: 45. (highly accessed and journal-featured article) Sun, Y.* 2015. Translational Horizons in the Tumor Microenvironment: Harnessing Breakthroughs and Targeting Cures. Med Res Rev. 35: 408-436. (cover page article) Chen, F., Qi, X., Qian, M., Dai, Y. and Sun, Y.* 2014. Tackling the Tumor Microenvironment: What Challenge Does It Pose to Anticancer Therapies? Protein Cell. 5: 816–826. Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L. and Nelson, P. S. 2012. Treatment-Induced Damage to the Tumor Microenvironment Promotes Prostate Cancer Therapy Resistance through WNT16B. Nat Med. 18: 1359-1368. Sun, Y. and Nelson, P. S. 2012. Molecular Pathways: Involving Microenvironment Damage Responses in Cancer Therapy Resistance. Clin Cancer Res. 18: 4019-4025. Bluemn, E. G., Paulson, K. G., Higgins, E. E., Sun, Y., Nghiem, P. and Nelson, P. S. 2009. Merkel Cell Polyomavirus is not Detected in Prostate Cancers, Surrounding Stroma, or Benign Prostate Controls. J Clin Virol. 44: 164-166. Coppé, J. -P., Patil, C. K., Rodier, F., Sun, Y., Mu？oz, D. P., Goldstein, J., Nelson, P. S., Desprez, P. –Y., and Campisi, J. 2008. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor. PLoS Biol. 6: 2853-2868. Sun, Y., Wong, N., Guan, Y., Salamanca, C. M., Cheng, J. C., Lee, J. M., Gray, J. W., and Auersperg, N. 2008. The Eukaryotic Translation Elongation Factor eEF1A2 Induces Neoplastic Properties and Mediates Tumorigenic Effects of ZNF217 in Precursor Cells of Human Ovarian Carcinomas. Int J Cancer. 123: 1761-1769. Li, P., Maines-Bandiera, S., Kuo, W., Guan, Y., Sun, Y., Hills, M., Huang, G., Collins, C. C., Leung, P. C. K., Gray, J. W. and Auersperg, N. 2007. Multiple Roles of the Candidate Oncogene ZNF217 in Ovarian Epithelial Neoplastic Progression. Int J Cancer. 120:1863-1873. Sun, Y., Bojikova-Fournier, S. and MacRae, T. H. 2006. Structural and Functional Roles for β-Strand 7 in the α-Crystallin Domain of p26, a Poly-disperse Small Heat Shock Protein from the Extremophile, Artemia franciscana. FEBS J. 273: 1020-1034. Villeneuve, T. S., Ma, X., Sun, Y., Oulton, M. M., Oliver, A. E. and MacRae, T. H. 2006. Inhibition of Apoptosis by p26: Implications for Small Heat Shock Protein Function during Artemia Development. Cell Stress & Chaperones. 11: 71-80. Ma, X., Jamil, K., MacRae, T. H., Clegg, J. S, Russell, J. M., Villeneuve, T. S., Euloth, M., Sun, Y., Crowe, J. H., Tablin, F. and Oliver, A. E. 2005. A Small Stress Protein Acts Synergistically with Trehalose to Confer Desiccation Tolerance on Mammalian Cells. Cryobiology. 51: 15-28. Sun, Y. and MacRae, T. H. 2005. Characterization of Novel Sequence Motifs within Amino- and Carboxy-Terminal Extensions of p26, a Small Heat Shock Protein from Artemia franciscana. FEBS J. 272: 5230-5243. Sun, Y. and MacRae, T. H. 2005. Small Heat Shock Proteins: Molecular Structure and Chaperone Function. Cell Mol. Life Sci. 62: 2460-2476. Sun, Y. and MacRae, T. H. 2005. The Small Heat Shock Proteins and their Role in Human Disease. FEBS J. 272: 2613-2627. Sun, Y., Mansour, M., Crack, J. A., Gass, G. L. and MacRae, T. H. 2004. Oligomerization, Chaperone Activity and Nuclear Localization of p26, a Small Heat Shock Protein from Artemia franciscana. J. Biol. Chem. 279: 39999-40006. Crack, J., Mansour, M., Sun, Y. and MacRae, T. H. 2002. Functional Analysis of a Small Heat Shock/alpha-Crystallin Protein from Artemia franciscana. Eur. J. Biochem. 269: 933-942. Chen, J., Fu, H., Que, Q., Lu, Z., Song, L. and Sun, Y. 1998. Effects of HSP70 Gene Expression on the Fertility of Sorghum. Dev. and Rep. Biol. 13: 51-62.