孫宇
職稱：研究員
學(xué)歷學(xué)位：博士 研究生
Email: [email protected], [email protected]
個(gè)人簡(jiǎn)介
美國(guó)國(guó)防部“青年科學(xué)家”獎(jiǎng)獲得者,，上海市“優(yōu)秀學(xué)術(shù)帶頭人”,。近年重點(diǎn)聚焦人類細(xì)胞衰老、組織微環(huán)境與增齡相關(guān)疾病的病理關(guān)聯(lián)與機(jī)制研究,，解析衰老細(xì)胞造成周邊微環(huán)境功能紊亂的主要途徑,，探索能夠選擇性靶向衰老細(xì)胞,、延緩組織穩(wěn)態(tài)失調(diào)和器官功能退行的干預(yù)方式,。迄今共發(fā)表SCI論文50多篇，個(gè)人他引超過(guò)8000次,，最高單篇引用達(dá)2900余次,。回國(guó)后以通訊作者在Nat Metab,、Nat Commun,、Aging Cell等國(guó)際權(quán)威期刊發(fā)表重要研究論文，應(yīng)邀在國(guó)際知名學(xué)術(shù)期刊撰寫綜述和評(píng)論多篇,。承擔(dān)中國(guó)科學(xué)院戰(zhàn)略性先導(dǎo)科技專項(xiàng),、國(guó)家重點(diǎn)研發(fā)計(jì)劃、國(guó)家自然科學(xué)基金等科研任務(wù),。在細(xì)胞衰老和增齡相關(guān)疾病領(lǐng)域的研究成果對(duì)相關(guān)學(xué)科的進(jìn)步起到了重要的推動(dòng)作用,，獲得國(guó)內(nèi)外同行的高度認(rèn)可。
個(gè)人簡(jiǎn)歷
2024-至 今：上海交通大學(xué)醫(yī)學(xué)院,，研究員
2017-2024年：中國(guó)科學(xué)院上海營(yíng)養(yǎng)與健康研究所 研究員
2014-2016年：中國(guó)科學(xué)院上海生命科學(xué)研究院/上海交通大學(xué)醫(yī)學(xué)院 健康科學(xué)研究所 研究員
2013-2013年：美國(guó)VA醫(yī)學(xué)中心,，聯(lián)邦研究員(PI)
2012-2013年：美國(guó)University of Washington，研究員,、助理教授(均為PI)
2006-2012年：美國(guó)Fred Hutchinson Cancer Research Center,，博士后、專職研究人員
2005-2006年：加拿大University of British Columbia產(chǎn)科與婦科學(xué)系,，博士后
2000-2005年：加拿大Dalhousie University生命科學(xué)學(xué)院,，哲學(xué)博士
1999-2000年：中國(guó)科學(xué)院基因組研究所，助理研究員
1996-1999年：中國(guó)科學(xué)院遺傳與發(fā)育生物學(xué)研究所,，理學(xué)碩士
1992-1996年：煙臺(tái)大學(xué)生物化學(xué)和微生物學(xué)系,，理學(xué)學(xué)士
研究方向
腫瘤微環(huán)境與臨床耐藥，細(xì)胞衰老和藥物靶向
研究?jī)?nèi)容
（1）腫瘤微環(huán)境與臨床耐藥
????腫瘤微環(huán)境,，即腫瘤細(xì)胞在體內(nèi)條件下賴以產(chǎn)生和存活的局部微環(huán)境(niche),。這一概念不僅包括了腫瘤細(xì)胞本身，更涉及周邊的良性基質(zhì)細(xì)胞,，后者涵蓋了數(shù)量眾多的成纖維細(xì)胞,、平滑肌細(xì)胞、內(nèi)皮細(xì)胞,、免疫和炎性細(xì)胞,、 神經(jīng)內(nèi)分泌細(xì)胞、膠質(zhì)細(xì)胞,、脂肪細(xì)胞,、周細(xì)胞等多種組分，以及它們產(chǎn)生的細(xì)胞間質(zhì),、微血管以及浸潤(rùn)在其中的生物活性分子,。
????腫瘤微環(huán)境在理化性質(zhì)方面與人體正常內(nèi)環(huán)境存在著許多不同,，比較顯著的是其低氧、低pH以及高壓的特點(diǎn),。 同時(shí),，腫瘤微環(huán)境中存在大量的蛋白水解酶、生長(zhǎng)因子,、細(xì)胞因子和趨化因子,，可以對(duì)腫瘤的增殖、侵襲,、粘附,、 血管生成以及抗癌治療效率等，造成不可低估的影響,，因而如何控制與阻滯微環(huán)境來(lái)源的這些負(fù)面影響,，則成為目 前醫(yī)學(xué)界集中探索的熱點(diǎn)與焦點(diǎn)。
（2）細(xì)胞衰老和藥物靶向
細(xì)胞是生物體結(jié)構(gòu)和功能的基本單位,，而細(xì)胞衰老在顯微形態(tài)上表現(xiàn)為細(xì)胞結(jié)構(gòu)的退行性改變,，包括細(xì)胞變大、輪廓變平,、胞核增大,、核仁膨脹、核膜凹陷,、溶酶體活性上升,。細(xì)胞衰老在生理學(xué)上的表現(xiàn)為功能衰退與代謝 紊亂，如細(xì)胞周期停滯,，細(xì)胞復(fù)制能力喪失,，對(duì)促有絲分裂刺激的反應(yīng)性減弱，對(duì)促凋亡因素的反應(yīng)性下降等,。
??實(shí)驗(yàn)室近期在脅迫條件下理化因素造成的包括DNA損傷在內(nèi)的生物大分子破壞導(dǎo)致細(xì)胞衰老的發(fā)生發(fā)展機(jī)制上取得一系列進(jìn)展,。其中，脅迫性衰老跟復(fù)制性衰老相似,，除了呈現(xiàn)以上典型細(xì)胞學(xué)特征之外,，尚表現(xiàn)為長(zhǎng)期、 慢性和強(qiáng)烈的衰老相關(guān)分泌表型(senescence-associated secretory phenotype, SASP),。該表型在核內(nèi)與胞內(nèi)多個(gè)信號(hào)通路組成的高度復(fù)雜的 信號(hào)網(wǎng)絡(luò)的作用下,，最終表現(xiàn)為級(jí)聯(lián)性放大和長(zhǎng)期性維持,。特別地,，老年人群或腫瘤患者在臨床條件下的SASP一旦形成，即難以停止或減退,，最終在一組關(guān)鍵因子的作用下成為無(wú)休循環(huán)(not-terminating cycle),。如何通過(guò)設(shè)計(jì)或篩選新型藥物,、針對(duì)SASP或衰老細(xì)胞進(jìn)行積極、精準(zhǔn)而高效的靶向干預(yù),，控制細(xì)胞衰老造成的組織失衡,、器官退行性變化等負(fù)面影響，是目前國(guó)際上衰老生物學(xué)和老年醫(yī)學(xué)迫切需要解決的關(guān)鍵問(wèn)題之一,。
代表論著（#第一作者,，*通訊作者）
1. Jiang, B., Zhang, W., Zhang, X. and Sun, Y*. 2024. Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy. Semin Cancer Biol. 101: 58-73.
2. Liu H, Xu Q, Wufuer H, Li Z, Sun R, Jiang Z, Dou X, Fu Q*, Campisi J*, Sun Y*. (2024). Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy. Aging Cell. 23(1): e13921.
3. Dou X, Fu Q, Long Q, Liu S, Zou Y, Fu D, Xu Q, Jiang Z, Ren X, Zhang G, Wei X, Li Q, Campisi J, Zhao Y*, Sun Y*. (2023). PDK4-dependent Hypercatabolism and Lactate Production of Senescent Cells Promotes Cancer Malignancy. Nat Metab. 5(11):1887-1910.
4. Wang C, Long Q, Fu Q, Xu Q, Fu D, Li Y, Gao L, Guo J, Zhang X, Lam EWF, Campisi J, Sun Y*. (2022). Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance. Oncogene. 41: 4941-4959.
5. Sun Y*, Li Q*, Kirkland JK*. (2022). Targeting Senescent Cells for a Healthier Longevity: the Roadmap for an Era of Global Aging. Life Med. 1(2):103-119.
6. Fu Q, Duan R, Sun Y*, Li Q*. (2022). Hyperbaric Oxygen Therapy for Healthy Aging: from Mechanisms to Therapeutics. Redox Biology. 53: 102352.
7.?Liu H, Zhao H, Sun Y*. (2021). Tumor Microenvironment and Cellular Senescence: Understanding Therapeutic Resistance and Harnessing Strategies. Semin Cancer Biol. 86(Pt 3): 769-781.
8.?Xu Q, Fu Q, Li Z, Liu H, Wang Y, Lin X, He R, Zhang X, Ju Z, Campisi J, Kirkland JK, Sun Y*. (2021) The Flavonoid Procyanidin C1 Has Senotherapeutic Activity and Increases Lifespan in Mice. Nat Metab 3(12):1706-1726.
9.?Liu H, Zhao H, Sun Y*. (2021) Tumor Microenvironment and Cellular Senescence: Understanding Therapeutic Resistance and Harnessing Strategies. Semin Cancer Biol 77(11):S1044-579X(21)00271-6.
10.?Song S, Tchkonia T, Jiang J, Kirkland JL, Sun Y*. (2020) Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities. Adv Sci 7(23):2002611.
11. Song S, Lam E, Tchkonia T, Kirkland J, Sun Y*. (2020) Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases. Trends Biochem Sci 45(7):578-592.
12.?Xu Q, Long Q, Zhu D, Fu D, Zhang B, Han L, Qian M, Guo J, Xu J, Cao L, Chin YE, Coppé JP, Lam E WF, Campisi J, Sun Y*. (2019) Targeting Amphiregulin (AREG) Derived from Senescent Stromal Cells Diminishes Cancer Resistance and Averts Programmed Cell Death 1 Ligand (PD-L1)-Mediated Immunosuppression. Aging Cell 18(6):e13027.
13. Han L, Lam E WF, Sun Y*. (2019) Extracellular Vesicles in the Tumor Microenvironment: Old Stories, But New Tales. Mol Cancer 18(1):59.
14.?Zhang B, Lam E WF, Sun Y*. (2019) Senescent Cells: A New Achilles' Heel to Exploit for Cancer Medicine? Aging Cell 18(1):e12875.
15.?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 YE, Lam E WF, Coppé JP, Sun Y*. (2018) Targeting SPINK1 in the Damaged Tumour Microenvironment Alleviates Therapeutic Resistance. Nat Commun 9(1):4315.
16.?Sun Y*, Coppé JP, Lam E WF. (2018) Cellular Senescence: the Sought or the Unwanted? Trends Mol Med 24(10):871-885.
17.?Zhang B, Fu D, Xu Q, Cong X, Wu C, Zhong X, Ma Y, Lv Z, Chen F, Han L, Qian M, Chin YE, Lam E WF, Chiao P, Sun Y*. (2018) The Senescence-Associated Secretory Phenotype Is Potentiated by Feedforward Regulatory Mechanisms Involving Zscan4 and TAK1. Nat Commun 9(1):1723.
18.?Zhang B, Chen F, Xu Q, Han L, Xu J, Gao L, Sun X, Li Y, Li Y, Qian M, Sun Y*. (2018) Revisiting Ovarian Cancer Microenvironment: a Friend or a Foe? Protein Cell 9(8):674–692.
19.?Han L, Xu J, Xu Q, Zhang B, Lam E WF, Sun Y*. (2017) Extracellular Vesicles in the Tumor Microenvironment: Therapeutic Resistance, Clinical Biomarkers and Targeting Strategies. Med Res Rev 37(6):1318-1349.
20.?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(7):842-851.
21.?Sun Y*. (2016) Tumor Microenvironment and Cancer Therapy Resistance. Cancer Lett 380(1):205–215.
22.?Xu Q, Chiao P, Sun Y*. (2016) Amphiregulin in Cancer: New Insights for Translational Medicine. Trends Cancer 2(3):111-113.
23.?Sun Y*, Zhu D, Chen F, Qian M, Wei H, Chen W, Xu J. (2016) SFRP2 Augments WNT16B Signaling to Promote Therapeutic Resistance in the Damaged Tumor Microenvironment. Oncogene 35(33):4321-4334.
24.?Zhang B, Sun Y*. (2015) Landscape and Targeting of the Angpt-Tie System in Current Anticancer Therapy. Transl Med 5(3):157.
25.?Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, Curran SC, Davalos AR, Wilson-Edell KA, Liu S, Limbad C, Demaria M, Li P, Hubbard GB, Ikeno Y, Javors M, Desprez PY, Benz CC, Kapahi P, Nelson PS, Campisi J. (2015) mTOR Regulates the Pro-Tumorigenic Senescence-Associated Secretory Phenotype by Promoting IL1A Translation. Nat Cell Biol 17(8):1049-1061.
26.?Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y, Hu G, Sun Y*. (2015) New Horizons in the Tumor Microenvironment Biology: Challenges and Opportunities. BMC Med 13:45.
27.?Sun Y*. (2015) Translational Horizons in the Tumor Microenvironment: Harnessing Breakthroughs and Targeting Cures. Med Res Rev 35(2):408-436.
28.?Chen F, Qi X, Qian M, Dai Y, Sun Y*. (2014) Tackling the Tumor Microenvironment: What Challenge Does It Pose to Anticancer Therapies? Protein Cell 5(11):816–826.
29.?Sun Y#, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS. (2012) Treatment-Induced Damage to the Tumor Microenvironment Promotes Prostate Cancer Therapy Resistance through WNT16B. Nat Med 18(9):1359-1368.
30.?Sun Y#, Nelson PS. (2012) Molecular Pathways: Involving Microenvironment Damage Responses in Cancer Therapy Resistance. Clin Cancer Res 18(15):4019-4025.
31. Bluemn EG, Paulson KG, Higgins EE, Sun Y, Nghiem P, Nelson PS. (2009) Merkel Cell Polyomavirus is not Detected in Prostate Cancers, Surrounding Stroma, or Benign Prostate Controls. J Clin Virol 44(2):164-166.
32.?Coppé JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez P–Y, Campisi J. (2008) Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor. PLoS Biol 6(12):2853-2868.
33.?Sun Y#, Wong N, Guan Y, Salamanca CM, Cheng JC, Lee JM, Gray JW, 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(8):1761-1769.
34.?Li P, Maines-Bandiera S, Kuo W, Guan Y, Sun Y, Hills M, Huang G, Collins CC, Leung PCK, Gray JW, Auersperg N. (2007) Multiple Roles of the Candidate Oncogene ZNF217 in Ovarian Epithelial Neoplastic Progression. Int J Cancer 120(9):1863-1873.
35.?Sun Y#, Bojikova-Fournier S, MacRae TH. (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(5):1020-1034.
36.?Sun Y#, MacRae TH. (2005) Characterization of Novel Sequence Motifs within Amino- and CarboxyTerminal Extensions of p26, a Small Heat Shock Protein from Artemia franciscana. FEBS J
272(20):5230-5243.
37.?Sun Y#, MacRae TH. (2005) Small Heat Shock Proteins: Molecular Structure and Chaperone Function. Cell Mol Life Sci 62(21):2460-2476.
38.?Sun Y#, MacRae TH. (2005) The Small Heat Shock Proteins and their Role in Human Disease. FEBS J 272(11):2613-2627.
39.?Sun Y#, Mansour M, Crack JA, Gass GL, MacRae TH. (2004) Oligomerization, Chaperone Activity and Nuclear Localization of p26, a Small Heat Shock Protein from Artemia franciscana. J Biol Chem 279(38):39999-40006.
