尹玉新
校长讲座教授, 教授
生物和遗传学博士(美国北卡罗莱纳大学)
医学博士(协和医科大学)
尹玉新教授1990年毕业于协和医科大学,获医学博士学位,1997年毕业于美国北卡罗莱纳大学(University of North Carolina at Chapel Hill) , 获分子生物学和遗传学博士学位,随后在普林斯顿大学做博士后,1999年加入美国哥伦比亚大学教授系列。 2008年回国加入北京大学医学部任淑范基金讲座教授和林松年基金讲座教授。尹玉新教授长期从事肿瘤发生机理的研究,主要关注抑癌基因在细胞周期调控、细胞凋亡和基因组稳定性中发挥的作用。
1992年,他以第一作者身份报道p53能够通过细胞周期检验点的调控控制人类基因组的稳定性(Cell, 1992),该工作首次揭示了p53抗癌基因的作用机理,被认为是肿瘤研究的里程碑式发现。1998年发现了p53指导细胞对环境压力反应的机理(Nature, 1998)。 2003年他的研究团队首次揭示出p53下游免疫组织特异性靶基因PAC1,从而在p53和免疫信号通路之间建立了联系(Nature, 2003)。其研究组还致力于抑癌基因PTEN 的研究,他们发现PTEN 是维持染色体功能和结构的柱石,失去PTEN 会导致染色体分裂异常和紊乱,从而导致肿瘤发生(Cell, 2007)。Cell在同期发表评论称此工作将PTEN研究带入核时代,Nature评论称发现了基因组的保护者。
2009年以来,尹玉新主持国家基础研究重大项目(973计划首席科学家)、科技部重大研发计划“蛋白质机器与生命过程调控“重点专项、国家自然科学基金重点项目、北京市自然科学基金重大项目,对蛋白质的复杂生物学功能开展了广泛探索,取得了一系列重要成果: 发现了新的蛋白编码机制,为鉴定新蛋白质和生物多样性提供了理论基础,并由此鉴定出PTEN家族的新亚型PTENα蛋白(Cell Metabolism, 2014),PTEN beta蛋白 (Nature Communications, 2017) 和PTEN epsilon (EMBO J. 2021);首次证实了PTEN C末端在维持基因组稳定性、抑制肿瘤发生中的重要作用(Cell Reports, 2014);研究还揭示PTEN 与Histone H1组成复合物参与染色体结构调节,并影响组蛋白修饰和下游基因转录调控(Cell Reports, 2014)。发现了 DNA复制的新机制(Cell Research, 2015),并且证明PTEN可以保护DNA复制叉以应对环境压力(Cell Reports, 2015)。 在肿瘤免疫探索方面, 揭示了T细胞免疫防御的调控机理,为肿瘤免疫确定了新方向和新靶标 (Nature Immunology, 2015,Nature Immunology, 2019)。近年他们还发现PTEN的甲基化修饰及其生理与病理意义(PNAS,2019)。他们也研究并设计相关新型化合药物,以抑制肿瘤生长,或激活免疫系统杀伤肿瘤细胞,促进肿瘤免疫治疗。近年来尹玉新团队成功地开发了基于人工智能代谢组学诊断癌症方法,致力于肿瘤早期诊断与治疗监测等应用, 目前已成功应用于肺癌和胰腺癌的早期筛查 (Science Advances, 2021, Science Translational Medicine, 2022 )。
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- Yin, Y.*, Liu, Y. X., Jin, Y. J., Hall, E. J., and Barrett, J. C. (2003). PAC1 phosphatase is a transcription target of p53 in signaling apoptosis and growth suppression. Nature 422:527-531.
- Shen, W. H., Balajee, A. B., Wang, J., Wu, H., Eng, C., Pandolfi, P. P., and Yin, Y.* (2007). Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128:157-170.
- Liang, H., He, S., Yang, J., Jia, X., Wang, P., Chen, X., Zhang, Z., Zou, X., McNutt, M.A., Shen, W.H.,* and Yin, Y.*. (2014). PTENα is a PTEN isoform Translated through Alternative Initiation and Regulates Mitochondrial Function. Cell Metab. 19, 836-848.
- Wang, G., Li, Y., Wang, P., Liang, H., Cui, M., Zhu, M., Guo, L., Su, Q., Sun, Y., McNutt, M.A., and Yin, Y.*. (2015). PTEN regulates RPA1 and protects DNA replication forks. Cell Res. 25, 1189-1204.
- Lu, D., Liu, L., Ji, X., Gao, Y., Chen, X., Liu, Y., Liu, Y., Zhao, X., Li, Y., Li, Y., Jin, Y., Zhang, Y., McNutt, M.A., Zhang, Y., and Yin, Y.*(2015).The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation. Nat Immunol., 16, 1263-1273.
- Feng, J., Liang, J., Li, J., Li, Y., Liang, H., Zhao, X., McNutt, M.A., and Yin, Y.* (2015). PTEN Controls the DNA Replication Process through MCM2 in Response to Replicative Stress. Cell Rep, 13, 1295-1303.
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- Wang P, Mei F, Hu J, Zhu M, Qi H, Chen X, Li R, McNutt MA, Yin, Y*. (2017) PTENα Modulates CaMKII Signaling and Controls Contextual Fear Memory and Spatial Learning. Cell Rep. 19(12):2627-2641.
- Li G, Yang J, Yang C, Zhu M, Jin Y, McNutt MA, Yin Y* (2018) PTENα regulates mitophagy and maintains mitochondrial quality control. Autophagy. 14(10): 1742-1760.
- Feng J., Dang Y., Zhang W., Zhao X., Zhang C., Hou Z., Jin Y., McNutt MA, Marks AR., Yin Y* (2019). PTEN arginine methylation by PRMT6 suppresses PI3K–AKT signaling and modulates pre-mRNA splicing. PNAS. 116(14):6868-6877.
- Li Y., Jin Y., Liu B., Lu D., Zhu M., Jin Y., McNutt MA, Yin Y* (2019). PTENα Promotes Neutrophil Chemotaxis through Regulation of Cell Deformability. Blood. pii: blood-2019-01-899864.
- Lu, D., Liu, L., Sun, Y., Song, J., Yin, Q., Zhang, G., Qi, F., Hu, Z., Yang, Z., Zhou, Z., Hu, Y., Zhang, L., Ji, J., Zhao, X., Jin, Y., McNutt, M. A., Yin, Y*. (2020). The phosphatase pac1 acts as a t cell suppressor and attenuates host antitumor immunity. Nat. Immunol. 21, 287-297
- Liang, L., Feng, J., Zuo, P., Yang, J., Lu, Y., Yin, Y*. (2020). Molecular basis for assembly of the shieldin complex and its implications for nhej. Nat. Commun. 11, 1972
- Zhang, Q., Liang, H., Zhao, X., Zheng, L., Li, Y., Gong, J., Zhu, Y., Jin, Y., Yin, Y*. (2021). Ptenepsilon suppresses tumor metastasis through regulation of filopodia formation. EMBO J. e105806
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- Wang, G., Qiu, M., Xing, X., Zhou, J., Yao, H., Li, M., Yin, R., Hou, Y., Li, Y., Pan, S., Huang, Y., Yang, F., Bai, F., Nie, H., Di, S., Guo, L., Meng, Z., Wang, J., Yin, Y*. (2022). Systematic analyses of early-stage lung cancer by scRNA-seq and lipidomic reveal aberrant lipid metabolism as detection biomarkers. Science Translational Medicine, 14(630):eabk2756.
- Zheng L, Liang H, Zhang Q, Shen Z, Sun Y, Zhao X, Gong J, Hou Z, Jiang K, Wang Q, Jin Y, Yin, Y*. (2022). circPTEN1, a circular RNA generated from PTEN, suppresses cancer progression through inhibition of TGF-β/Smad signaling. Mol Cancer. 21(1):41.
- Zhou N, Qi H, Liu J, Zhang G, Liu J, Liu N, Zhu M, Zhao X, Song C, Zhou Z, Gong J, Li R, Bai X, Jin Y, Song Y, Yin Y*.(2022). Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses.Cell Metab. 34(7):1023-1041.e8.
- Song J, Zhao W, Zhang X, Tian W, Zhao X, Ma L, Cao Y, Yin Y, Zhang X, Deng X, Lu D. (2022). Mutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling. Nat Commun. 13(1):7096.
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- Shi P, Ren X, Meng J, Kang C, Wu Y, Rong Y, Zhao S, Jiang Z, Liang L, He W, Yin Y, Li X, Liu Y, Huang X, Sun Y, Li B, Wu C.(2022).Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS. Nat Commun. 13(1):2673.
- Mei F, Hu J, Wu Z, Zhang G, Liu A, Li X, Zhu M, Gan Y, Liang L, Zhao X, Yuan Y, Meng X, Li Y, Jin Y, Jia J, Yin Y*.(2022). FAM69C, a kinase critical for synaptic function and memory, is defective in neurodegenerative dementia. Cell Rep. 40(3):111101.
- Yin Q, Li Y, Zhou Z, Li X, Li M, Liu C, Dong D, Wang G, Zhu M, Yang J, Jin Y, Guo L, Yin Y*.(2022). RPA1 controls chromatin architecture and maintains lipid metabolic homeostasis. Cell Rep. 40(2):111071.
- Lu Y., Zuo P., Chen H., Shan H., Wang W., Dai Z., Xu H., Chen Y., Liang L., Ding D., Jin Y., Yin Y.*. (2023). Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP2. Nat Commun. 14(1):6157.
- Hao W, Zhang H, Hong P, Zhang X, Zhao X, Ma L, Qiu X, Ping H, Lu D, Yin Y*.(2023). Critical role of VHL/BICD2/STAT1 axis in crystal-associated kidney disease.Cell Death Dis. 14(10):680.
- Song J, Liu Y, Yin Y, Wang H, Zhang X, Li Y, Zhao X, Zhang G, Meng X, Jin Y, Lu D, Yin Y*.(2023). PTIR1 acts as an isoform of DDX58 and promotes tumor immune resistance through activation of UCHL5. Cell Rep. 42(11):113388.
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