邮箱: yingwang@sinh.ac.cn
电话: +86-21-54923350
所属部门: 中国科学院肿瘤与微环境重点实验室
2017-至 今:中国科学院上海营养与健康研究所 研究员
2015-2016年:中国科学院上海生命科学研究院 研究员
2011-2015年:中国科学院上海生命科学研究院 副研究员
2009-2011年:德国明斯特大学 博士后
2006-2009年:上海交通大学 医学免疫 博士
2003-2006年:上海交通大学 医学免疫 硕士
慢性疾病微环境的功能与调控
在慢性疾病发生发展过程中,损伤组织微环境中多种细胞(免疫细胞、基质细胞、组织干细胞、内皮细胞等)、可溶性分子(细胞因子、生长因子、代谢产物等)、细胞外基质、pH值和氧浓度等均处于动态变化,并交互调控影响疾病的病理进程。本研究组重点研究慢性疾病组织微环境的特征和功能调控:
1. 疾病组织微环境中组织干细胞演变特性和形成机制:重点研究慢性疾病(肥胖、肿瘤、自身免疫病等)组织微环境中组织干细胞的识别和演变特征,明确决定组织干细胞特性演变的关键机制,揭示疾病微环境中组织干细胞对相关疾病的调控作用和机制;
2. 疾病组织微环境中免疫细胞动态演变机制与慢性疾病治疗:重点研究疾病组织微环境中髓系细胞(如巨噬细胞、中性粒细胞等)的动态演变机制,及其调控在多种慢性疾病(肥胖及其相关胰岛素抵抗、肿瘤、自身免疫病等)治疗中的应用潜能;
3. 代谢与免疫调节:重点研究组织微环境中代谢物的变化特征及其调控免疫反应的关键机制。
1. Lin L, Hu M, Li Q, Du L, Lin L, Xue Y, Zheng F, Wang F, Liu K, Wang Y, Ye J, Jiang X, Wang X, Wang J, Zhai J, Liu B, Xie H, You Y, Wang J, Kong X, Feng D, Green DR, Shi Y*, Wang Y*. Oleic acid availability impacts thymocyte preprogramming and subsequent peripheral Treg cell differentiation. Nat Immunol 2024 Jan;25(1):54-65.
2. Li Q, Lin L, Shou P, Liu K, Xue Y, Hu M, Ling W, Huang Y, Du L, Zheng C, Wang X, Zheng F, Zhang T, Wang Y, Shao C, Melino G, Shi Y*, Wang Y*. MHC class Ib-restricted CD8+ T cells possess strong tumoricidal activities. Proc Natl Acad Sci U S A 2023 Oct 24;120(43):e2304689120.
3. Wang Y, Xu M, Sun J, Li X, Shi H, Wang X, Liu B, Zhang T, Jiang X, Lin L, Li Q, Huang Y, Liang Y, Hu M, Zheng F, Zhang F, Sun J, Shi Y*, Wang Y*. Glycolytic neutrophils accrued in the spleen compromise anti-tumour T cell immunity in breast cancer. Nat Metab 2023 Aug;5(8):1408-1422.
4. Xue YQ, Lin LY, Li Q, Hu MY, Zhai JJ, Cao JC, Qin J, Sorokin L, Shi Y*, Wang Y*. SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes. Adv Sci (Weinh) 2023 Feb;10(4):e2201949.
5. Wang Y, Fang JK, Liu BM, Shao CS, Shi Y. Reciprocal regulation of mesenchymal stem cells and immune responses. Cell Stem Cell 2022 Nov 3;29(11):1515-1530.
6. Zhang T, Wang Y, Li Q, Lin L, Xu C, Xue Y, Hu M, Shi Y*, Wang Y*. Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity. Oncogene 2022 Mar;41(13):1866-1881.
7. Zheng Z, Li YN, Jia S, Zhu M, Cao L, Tao M, Jiang JT, Zhan SH, Chen YJ, Gao PJ, Hu WG, Wang Y*, Shao CS*, Shi YF*. Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3. Nat Commun 2021 Oct 27;12(1):6202.
8. Gan Y, Zhang T, Chen X, Cao W, Lin L, Du L, Wang Y, Zhou F, He X, He Y, Gan J, Sheng H, Sorokin L, Shi Y*, Wang Y*. Steroids enable mesenchymal stromal cells to promote CD8+T cell proliferation via VEGF-C. Adv Sci (Weinh) 2021 May 2;8(12):2003712.
9. Wang X, Lin L, Lan B, Wang Y, Du L, Chen X, Li Q, Liu K, Hu M, Xue Y, Roberts Art, Shao C, Melino G, Shi Y*, Wang Y*. IGF2R-initiated proton rechanneling dictates an anti-inflammatory property in macrophages. Sci Adv 2020 Nov 25;6(48):eabb7389.
10. Zhang X#, Wang Y#, Song J#, Gerwien H, Chuquisana O, Chashchina A, Denz C, Sorokin L. The endothelial basement membrane acts as a checkpoint for entry of pathogenic T cells into the brain. J Exp Med 2020 Jul 6;217(7):e20191339.
11. Liu K, Lin L, Li Q, Xue Y, Zheng F, Wang G, Zheng C, Du L, Hu M, Shao C, Kong X, Melino G, Shi Y*, Wang Y*. Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II. Proc Natl Acad Sci U S A 2020 Feb 4;117(5):2462-2472.
12. Du L, Lin LY, Li Q, Liu KL, Huang Y, Wang XF, Cao K, Chen XD, Cao W, Li FY, Shao CS, Wang Y*, Shi Y*. IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-dependent Anti-inflammatory Properties. Cell Metab 2019 Jun 4;29(6):1363-1375.e8.
13. Huang Y, Li Q, Zhang K, Hu M, Wang Y, Du L, Lin L, Li S, Sorokin L, Melino G, Shi Y*, Wang Y*. Single cell transcriptomic analysis of human mesenchymal stem cells reveals limited heterogeneity. Cell Death Dis 2019 May 8;10(5):368.
14. Shi Y*, Wang Y, Li Qing, Liu KL, Hou JQ, Shao CS, Wang Y*. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nepherol 2018 Aug;14(8):493-507.
15. Wang G, Cao K, Liu K, Xue Y, Roberts AI, Li F, Han Y, Rabson AB, Wang Y*, Shi Y*. Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells. Cell Death Differ 2018 Jul;25(7):1209-1223.
16. Shi Y, Du L, Lin L, Wang Y*. Tumour associated mesenchymal stem/stromal cells: emerging therapeutic targets. Nat Rev Drug Discov 2017 Jan;16(1):35-52.
17. Song J, Zhang X, Buscher K, Wang Y, Wang H, Di Russo J, Li L, Lütke-Enking S, Zarbock A, Stadtmann A, Striewski P, Wirth B, Kuzmanov I, Wiendl H, Schulte D, Vestweber D, Sorokin L. Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration. Cell Rep 2017 Jan 31;18(5):1256-1269.
18. Yu P, Huang Y, Han Y, Lin L, Rabson A, Wang Y*, Shi Y*. TNFα-activated mesenchymal stromal cells promote breast cancer metastasis through recruiting CXCR2+ neutrophils. Oncogene 2017 Jan 26;36(4):482-490.
19. Lin LY, Du LM, Cao K, Huang Y, Yu PF, Zhang LY, Li FY, Wang Y*, Shi YF*. Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities. Oncogene 2016 Nov 17;35(46):6038-6042.
20. Shou P, Chen Q, Jiang J, Xu C, Zhang J, Jiang M, Velletri T, Cao W, Huang Y, Yang Q, Han X, Zhang L, Wei L, Rabson A, Chin YE, Wang Y*, Shi Y*. Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells. Oncogene 2016 Nov 17;35(46):5953-5962.
21. Jiang M, Zheng C, Shou P, Li N, Cao G, Chen Q, Xu C, Du L, Yang Q, Cao J, Han Y, Li F, Cao W, Liu F, Rabson AB, Roberts AI, Xie W, Wang Y*, Shi Y*. SHP1 regulates bone mass by directing mesenchymal stem cell differentiation. Cell Rep 2016 Jul 19;16(3):769-780.
22. Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, Xu C, Zhang L, Yang H, Hou J, Wang Y*, Shi Y*. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ 2016 Jul;23(7):1128-1139.
23. Zheng C, Yang Q, Cao J, Xie N, Liu K, Shou P, Qian F, Wang Y*, Shi Y*. Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death Dis 2016 Mar 31;7(3):e2167.
24. Zheng C, Yang Q, Xu C, Shou P, Cao J, Jiang M, Chen Q, Cao G, Han Y, Li F, Cao W, Zhang L, Zhang L, Shi Y*, Wang Y*. CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. Proc Natl Acad Sci U S A 2015 Dec 29;112(52):E7239-E7248.
25. Shi Y, Cao J, Wang Y*. Rethinking regeneration: empowerment of stem cells by inflammation. Cell Death Differ 2015 Dec;22(12):1891-1892.
26. Cao K, Wang G, Li W, Zhang L, Wang R, Huang Y, Du L, Jiang J, Wu C, He X, Roberts AI, Wang Y*, Shi Y*. Histone deacetylase inhibitors prevent activation-induced cell death and promote anti-tumor immunity. Oncogene 2015 Dec 3;34(49):5960-5970.
27. Song J, Wu C, Korpos E, Zhang X, Agrawal S, Wang Y, Faber C, Schafers M, Korner H, Opdenakker G, Hallmann R, Sorokin L. Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration. Cell Rep 2015 Feb 24;10(7):1040-1054.
28. Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol 2014 Nov;15(11):1009-1016.
29. Xu C, Lin L, Cao G, Chen Q, Shou P, Huang Y, Han Y, Wang Y*, Shi Y*. Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo. Oncogene 2014 Oct 16;33(42):5047-5052.
30. Huang Y, Yu P, Li W, Ren G, Roberts AI, Cao W, Zhang X, Su J, Chen X, Chen Q, Shou P, Xu C, Du L, Lin L, Xie N, Zhang L, Wang Y*, Shi Y*. p53 regulates mesenchymal stem cell-mediated tumor suppression in a tumor microenvironment through immune modulation. Oncogene 2014 Jul 17;33(29):3830-3838.
31. Ma S, Xie N, Li W, Yuan B, Shi Y*, Wang Y*. Immunobiology of mesenchymal stem cells. Cell Death Differ 2014 Feb;21(2):216-225.
32. Ren G, Zhao X, Wang Y, Zhang X, Chen XD, Xu CL, Yuan ZR, Roberts AI, Zhang LY, Zheng B, Wen T, Han YY, Rabson AB, Tischfield JA, Shao CS, Shi YF. Tumor resident mesenchymal stromal cells promote tumor development through CCR2-dependent recruitment of monocytes/macrophages. Cell Stem Cell 2012 Dec 7;11(6):812-824.
33. Shi Y, Wei L, Wang Y, Ren G. Stem cells deployed for bone repair hijacked by T cells. Cell Stem Cell 2012 Jan 6;10(1):6-8.
34. Wang Y, Luo Q, Xu Y, Feng D, Fei J, Cheng Q, Xu L. γ-aminobutyric acid transporter 1 negatively regulates T cell activation and survival through protein kinase C-dependent signaling pathways. J Immunol 2009 Sep 1;183(5):3488-3495.
35. Wang Y, Feng D, Liu G, Luo Q, Xu Y, Lin S, Fei J, Xu L. γ-aminobutyric acid transporter 1 negatively regulates T cell-mediated immune responses and ameliorates autoimmune inflammation in the CNS. J Immunol 2008 Dec 15;181(12):8226-8236.
36. Wang Y, Mei Y, Fend D, Xu L. Triptolide modulates T cell inflammatory responses and ameliorates experimental autoimmune encephalomyelitis. J Neurosci Res 2008 Aug 15;86(11):2441-2449.
37. Wang Y, Mei Y, Bao S, Xu L. Vasoactive intesinal polypeptide enhances oral tolerance by regulating both cellular and humoral immune responses. Clin Exp Immunol 2007 Apr;148(1):178-187.
38. Wang Y, Mei Y, Feng D, Xu L. (-)-epigallocatechin-3-gallate protects mice from concanavalin A-induced hepatitis through suppressing immune mediated liver injury. Clin Exp Immunol 2006 Sep;145(3):485-492.