科学研究
肿瘤多组学与免疫治疗研究组
  作者:  2020-12-18

基本信息

叶幼琼

电话:63846590-776772

邮箱:youqiong.ye@shsmu.edu.cn


个人简历

叶幼琼,博士,研究员,上海交通大学医学院上海市免疫学研究所肿瘤多组学与免疫治疗组课题组组长。2016年12月获得同济大学博士学位,2017-2019年德克萨斯大学休斯顿健康科学中心从事博士后研究。致力于肿瘤发生、肿瘤微环境与肿瘤免疫治疗相关研究,从事包括基因组学、转录组学、蛋白质组学、表观基因组学和代谢组学在内的癌症多组学数据挖掘,以揭示癌症的相关调节机制,为临床治疗提供参考,帮助个性化或精准化癌症治疗。系列研究成果以第一/共一、共同通讯作者发表在Nature Metabolism、Nature Immunology、Cancer Cell、Cell Systems、Nature Communications等国际知名期刊。


研究方向

以肿瘤为研究对象,利用生物信息学手段和实验临床相结合分析大规模多组学数据揭示肿瘤与免疫治疗相关的调控机制,为肿瘤的临床治疗提供参考,以帮助个性化或精确化癌症治疗。主要研究内容包括 (1)开发/应用计算方法分析肿瘤多组学数据以识别肿瘤疾病标志物和药物靶标,探索肿瘤的发生和发展机制。(2)基于肿瘤组织和单细胞的多组学揭示肿瘤微环境相关免疫特征以辅助肿瘤免疫治疗。(3)基于靶向的药物治疗或化疗的治疗前后的组学数据,建立分析模型,筛选适用性强、疗效好、副作用小的辅助药物与免疫治疗相结合以提高免疫治疗效果。


科研项目

1) 20ZR1472900,MMP2 / 9的小分子抑制剂SB-3CT通过调节PD-L1以增强肿瘤免疫治疗疗效,上海市自然科学基金项目 (原创探索类),2020.7-2023.6,50万元,项目负责人

2) 20PJ1412800,基于单细胞测序等方法解析结直肠癌微环境细胞互作以探索潜在治疗靶点,上海市浦江人才计划, 2020.11-2022.10,30万元,项目负责人

3) 82073145,基于肿瘤组织/单细胞的多组学揭示低氧相关免疫特征以 辅助肿瘤免疫治疗,国家自然科学基金 (面上项目),2021.01-2024.12,55万元,项目负责人


论文与专著


代表性论著(第一或共同一作、共同通讯)

1) Ye Y. (第一/共同通讯作者), Kuang X., Xie Z., Liang L., Zhang Z., Zhang Y., Ma F., Gao, Q., Chang R., Zhao S., Su J., Li, H., Peng, J., Chen H., Yin M., Peng C., Yang N., Liu J., Liu H., Han L., Chen X.. Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1. Genome Medicine (2020) 12:83.

2) Ye Y. (第一作者), Jing Y., Li L., Mills G.B., Diao L., Liu H., Han L. Sex-associated molecular differences for cancer immunotherapy. Nature Communications, 2020,11:1779.  

3) Chang G., Shi L., Ye Y. (共同第一作者), Shi H., Zeng L, Tiwary S., Chang G., Huse J.T., Huo L., Ma L., Ma Y., Zeng L., Zhang S., Zhu J., Han L., He C. & Huang S. Genetic and Epigenetic Changes in YTHDF3 Promote Multiple Steps of Breast Cancer Brain Metastasis. Cancer Cell (2020) 38:1-15

4) Ye Y. (第一作者), Zhang Z., Liu Y., Han L. A multi-omics perspective for quantitative trait loci. Trends Genetics,2020.  

5) Hui Li, Kuang X., Liang, L., Ye Y. (第一作者), Zhang Y, Li J., Ma F., Tao J., Lei G., Zhao S., Su J., Yang N., Peng C., Xu X., Hung .-C., Han ., Liu H., Liu J., & Chen X. The beneficial role of Sunitinib in tumor immune surveillance by regulating tumor PD-L1. Advanced Science (2020)6, 1–16.

6) Ye Y. (第一作者), Hu Q., Chen H., Liang K., Yuan Y., Xiang Y., Ruan H., Zhang Z., Song A., Zhang H., Liu L., Diao L., Lou Y., Zhou B., Wang L., Zhou S., Gao J., Jonasch E., Lin S.H. Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nature Metabolism, 2019,1, 431–444.  

7) Zhang Z., Ye Y. (共同第一作者), Gong J., Ruan H., Liu C., Xiang Y., Cai C., Guo A., Ling J., Diao L., Weinstein J.N. & Han L..Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers. Communications Biology, 2018,1, 234.  

8) Hu Q., Ye Y.  (共同第一作者), Chan L.-C., Li Y., Liang K., Lin A., Egranov S.D., Zhang Y., Xia W., Gong J., Pan Y., Chatterjee S.S., Yao J., Evans K.W., Nguyen T.K., Park P.K., Liu J., Coarfa C., Donepudi S.R. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature Immunology, 2019,20, 835–851.  

9) Ye Y. (第一作者), Xiang Y., Ozguc F.M., Kim Y., Liu C.J., Park P.K., Hu Q., Diao L., Lou Y., Lin C., Guo A.Y., Zhou B., Wang L., Chen Z., Takahashi J.S., Mills G.B., Yoo S.H. & Han L.The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy. Cell System, 2018,6, 314-328.E2.  

10) Xiang Y., Ye Y. (共同第一作者), Zhang Z. & Han L. Maximizing the Utility of Cancer Transcriptomic Data. Trends in Cancer, 2018,4, 823–837.  

11) Xiang Y., Ye Y.  (共同第一作者), Lou Y., Yang Y., Cai C., Zhang Z., Mills T., Chen N., Kim Y., Ozguc F.M., Diao L., Karmouty-quintana H., Xia Y., Kellems R., Chen Z., Yoo S., Shyu A., Mills G.B. & Han L. Comprehensive characterization of alternative polyadenylation in human cancer. Journal of the National Cancer Institute, 2018,110, 379–389.  

12) Ye Y. (第一作者), Li M., Gu L., Chen X., Shi J., Zhang X. & Jiang C. Chromatin remodeling during in vivo neural stem cells differentiating to neurons in early Drosophila embryos. Cell Death and Differentiation, 2017,24, 409–420.  


共同作者

13) Liu, H., Kuang, X., Zhang, Y., Ye, Y., Li, J., Liang, L., Xie, Z., Weng, L., Guo, J., Li, H., Ma, F., Chen, X., Zhao, S., Su, J., Yang, N., Fang, F., Xie, Y., Tao, J., Zhang, J., Chen, X. ADORA1 Inhibition Promotes Tumor Immune Evasion by Regulating the ATF3-PD-L1 Axis. Cancer Cell, 37(3), (2020). 324-339.e8.

14) Jing, Y., Liu, J., Ye, Y., Pan, L., Deng, H., Wang, Y., Yang, Y., Diao, L., Lin, S. H., Mills, G. B., Zhuang, G., Xue, X., & Han, L. (2020). Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy. Nature Communications, 11(1), 1–7.

15) Hong, W., Ruan, H., Zhang, Z., Ye, Y., Liu, Y., Li, S., Jing, Y., Zhang, H., Diao, L., Liang, H., & Han, L. (2020). APAatlas: Decoding alternative polyadenylation across human tissues. Nucleic Acids Research, 48(D1), D34–D39.

16) Zhang, Z., Jing, J., Ye, Y., Chen, Z., Jing, Y., Li, S., Hong, W., Ruan, H., Liu, Y., Hu, Q., Wang, J., Li, W., Lin, C., Diao, L., Zhou, Y., & Han, L. Characterization of the dual functional effcts of heat shock proteins (HSPs) in cancer hallmarks to aid development of HSP inhibitors. Genome Medicine (2020). 12(1)

17) Liu, Y., Ruan, H., Li, S., Ye, Y., Hong, W., Gong, J., Zhang, Z., Jing, Y., Zhang, X., Diao, L., & Han, L. The genetic and pharmacogenomic landscape of snoRNAs in human cancer. Molecular Cancer (2020). 19(1), 1–7.

18) Zhang, Z., Lee, J., Ruan H., Ye Y., Krakowiak, J., Hu, Q., Xiang, X., Gong, J., et al. Dr. Bingying Zhou, Li Wang, Chunru Lin, Dr. Lixia Diao, Mills G., Li W., HanL. Nature Communications (2019). 10 (1), 1-15.

19) Hong, W., Ruan H., Zhang, Z., Ye Y., Liu Y., Li, S., Jing, Y., Zhang, H., Diao, L., Liang, H., Han, L. APAatlas: decoding alternative polyadenylation across human tissues (2019). gkz876.

20) Ruan H., Xiang Y., Ko J., Li S., Jing Y., Zhu X., Ye Y., Zhang Z., Mills T., Feng J., Liu C.-J., Jing J., Cao J., Zhou B., Wang L., Zhou Y., Lin C., Guo A.-Y., Chen X. et al. Comprehensive characterization of circular RNAs in ~1000 human cancer cell lines. Genome Medicine (2019). 1–14.

21) Chen X., Ye Y., Gu L., Sun J., Du Y., Liu W., Li W., Zhang X. & Jiang C. H3K27me3 signal in the cis regulatory elements reveals the differentiation potential of progenitors in Drosophila neuroglial development. Genomics, Proteomics & Bioinformatics (2019).

22) Zhang Q., Zhang Q., Jiang X., Ye Y., Liao H., Zhu F., Yan J., Luo L., Tian L., Jiang C., Chen Y., Liang X. & Sun Y. Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN. Theranostics (2019). 9, 986–1000.

23) Yuan B., Liu J., Cao J., Yu Y., Zhang H., Wang F., Zhu Y., Xiao M., Liu S., Ye Y., Ma L., Xu D., Xu N., Li Y., Zhao B., Xu P., Jin J., Xu J., Chen X. et al. PTPN3 acts as a tumor suppressor and boosts TGF‐β signaling independent of its phosphatase activity. The EMBO Journal (2019). e99945.

24) Nohara K., Mallampalli V., Nemkov T., Wirianto M., Yang J., Ye Y., Sun Y., Han L., Esser K.A., Mileykovskaya E., D’Alessandro A., Green C.B., Takahashi J.S., Dowhan W., Yoo S.-H. & Chen Z. Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge. Nature Communications (2019). 10, 3923.

25) Adebiyi M.G., Zhao Z., Ye Y., Manalo J., Hong Y., Lee C.C., Xian W., McKeon F., Culp-Hill R., D’ Alessandro A., Kellems R.E., Yoo S.-H., Han L. & Xia Y. Circadian period 2: a missing beneficial factor in sickle cell disease by lowering pulmonary inflammation, iron overload, and mortality. The FASEB Journal (2019). fj.201900246RR.

26) Zhang Z., Ruan H., Liu C.-J., Ye Y., Gong J., Diao L., Guo A.-Y. & Han L. tRic: A user-friendly data portal to explore the expression landscape of tRNAs in human cancers. RNA biology (2019). 1.

27) Neve, I., Sowa, J., Lin, C., Sivaramakrishnan,P., Ye, Y., Han, L., Herman, C., Wang, M. Escherichia coli Metabolite Profiling Leads to the Development of an RNA Interference Strain for Caenorhabditis elegans. Genes, Genomes, Genetics (2019).

28) Hu Q., Li C., Wang S., Li Y., Wen B., Zhang Y., Liang K., Yao J., Ye Y., Hsiao H., Nguyen T.K., Park P.K., Egranov S.D., Hawke D.H., Marks J.R., Han L., Hung M.-C., Zhang B., Lin C. et al. LncRNAs-directed PTEN enzymatic switch governs epithelial–mesenchymal transition. Cell Research (2019). 29, 286–304.

29) Tan P., Ye Y., He L., Xie J., Jing J., Ma G., Pan H., Han L., Han W. & Zhou Y. TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10. PLoS biology (2018). 16, e3000051.

30) Hu J., Gu L., Ye Y., Zheng M., Xu Z., Lin J., Du Y., Tian M., Luo L., Wang B., Zhang X., Weng Z. & Jiang C. Dynamic placement of the linker histone H1 associated with nucleosome arrangement and gene transcription in early Drosophila embryonic development. Cell Death & Disease (2018). 9, 765.

31) Zhang Q., Huang R., Ye Y., Guo X., Lu J., Zhu F., Gong X., Zhang Q., Yan J., Luo L., Zhuang S., Chen Y., Zhao X., Evans S.M. & Jiang C. Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversi fi cation. Cell Death and Disease (2018).

32) Gong J., Mei S., Liu C., Xiang Y., Ye Y., Zhang Z., Feng J., Liu R., Diao L., Guo A.-Y., Miao X. & Han L. PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer types. Nucleic Acids Research (2017). 46, D971–D976.

33) Gong J., Li Y., Liu C. jie, Xiang Y., Li C., Ye Y., Zhang Z., Hawke D.H., Park P.K., Diao L., Putkey J.A., Yang L., Guo A.Y., Lin C. & Han L. A Pan-cancer Analysis of the Expression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer. Cell Reports (2017). 21, 1968–1981.

34) Shi J., Zheng M., Ye Y., Li M., Chen X., Hu X., Sun J., Zhang X. & Jiang C. Drosophila Brahma complex remodels nucleosome organizations in multiple aspects. Nucleic acids research (2014). 42, 9730–9.

35) Fu Y., Huang C., Xu X., Gu H., Ye Y., Jiang C., Qiu Z. & Xie X. Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails. Cell Research (2015). 25, 1013–1024.


章节论著(#共同通讯)

36) Tan P. #, Ye Y.#, Mao J., He L: Autophagy- and Immune-Related Diseases. In: Cui J Ed. Autophagy Regulation of Innate Immunity, Advances in Experimental Medicine and Biology. 2019.

37) Liu Y., Ye Y., Gong J., Han L: Expression Quantitative Trait Loci (eQTL) Analysis in Cancer. In Walker J Ed. Methods in Molecular Biology ISSN: 1064-3745. 2019.


荣誉与奖励

2020年上半年上海市海外高层次人才计划

2020年上海市浦江人才A类(科研开发)


团队介绍

本课题组形成由课题组长、助理研究员、实验师、博士后、博士和硕士研究生组成的富有活力的科研研究团队。本团队致力于利用多组学大数据和生物信息学手段揭示肿瘤微环境与肿瘤治疗相关的调控机制,并与生物学家及临床医生协同合作,实现生物信息数据分析的实验和临床验证。


成员组成

杜艳华,博士,助理研究员

2017年6月至2020年6月,在同济大学医学院进行博士后训练;2011年9月至2017年5月就读于同济大学生命与科学技术学院生物信息学专业,获博士学位。主要研究领域为利用多组学高通量测序技术(scRNA-seq;ChIP-seq;ATAC-seq;WGBS;Exon-seq等)研究神经发育过程中的表观调控机制,研究成果发表于Cell Death Differ,iScience,Cell Research ,Stem Cell Reports,Stem Cells 等杂志。


包汝娟,硕士,实验师

于2016年7月在西安交通大学医学院取得生物化学与分子生物学专业硕士学位。目前在团队中承担基于不同转录组平台和病人队列构建结直肠癌预后模型及蛋白组学数据分析的工作。


董宇,博士后

2015年9月至2020年3月就读于上海交通大学系统生物医学研究院生物信息学专业,获博士学位。主要从事肿瘤相关的研究,利用高通量多组学数据和单细胞测序(RNAseq、WGS、WES, ChIP-seq、Proteomics、scRNAseq),为临床诊断和治疗提供线索,后续研究将聚焦于肿瘤与免疫治疗相关方向。研究成果发表于proteomics,frontier in genetics等杂志


王高阳,2019级硕士研究生


荀臻臻,2020级博士研究生


联系方式

办公室地址: 上海市重庆南路280号5号楼6楼607室

办公室电话: 021-63846590-776772

实验室地址: 上海市重庆南路280号5号楼6楼607室

实验室电话: 021-63846590-776772

邮 箱: youqiong.ye@shsmu.edu.cn