zyou(at)cimrbj.ac.cn
尤忠胜实验室致力于解析细胞基因组维持、RNA质量监测与先天免疫调控的核心机制与相互作用，并在此基础上，推动针对肿瘤和自身免疫疾病的新型治疗策略与药物的开发。
1. 基因组稳定性、RNA质量监测缺陷与先天免疫系统的相互作用
1. 发现一条由胞质DNA激发、Ca2+介导的新型信号通路，该通路在DNA复制叉保护和基因组稳定性维持中发挥关键作用 (Molecular Cell, 2019; Molecular Cell, 2023; Nature Communications, 2024)
2. 发现了离子通道蛋白TRPV2与先天免疫因子STING在内质网上的相互作用，该互作调控细胞内Ca2+水平，并决定先天免疫应答系统的静息与激活状态 (Molecular Cell, 2023; Cell Reports, in revision)
3. 构建了多个NMD报告系统，筛选并鉴定出多个NMD抑制剂及调控因子，揭示细胞内Ca2+浓度和持续性DNA损伤对NMD活性的影响 (Nature Medicine, 2014; Journal of Biological Chemistry, 2017)
4. 发现NMD通路是携带剪接体基因突变的血液肿瘤的潜在治疗靶点 (Cancer Research, 2021)
Kong L*, Cheng C*, Cheruiyot A, Yuan J, Yang Y, Hwang S, Foust D, Tsao N, Wilkerson E, Mosammaparast N, Major MB, Piston DW, Li S#, You Z#. TCAF1 Promotes TRPV2-mediated Ca2+ Release in Response to Cytosolic DNA to Protect Stressed Replication Forks. Nature Communications, 2024, 15: 4609. DOI: 10.1038/s41467-024-48988-6
Li S*, Kong L*, Meng Y, Cheng C, Lemacon DS, Yang Z, Tan K, Cheruiyot A, Lu Z and You Z . Cytosolic DNA Sensing by cGAS/STING Promotes TRPV2-Mediated Ca2+ Release to Protect Stressed Replication Forks. Molecular Cell, 2023, 83: 556-573. DOI: 10.1016/j.molcel.2022.12.034
Yang Z, Lemacon DS, Li S, Cheruiyot A, Kong L, Tan K, Cheng C, Turkay E, He D and You Z. A Context-dependent Pro- and Anti-resection Roles of ZKSCAN3 in Regulating Fork Resection during Replication Stress. Journal of Biological Chemistry, 2022, 29: 102215. DOI: 10.1016/j.jbc.2022.102215
Cheruiyot A*, Li S*, Nonavinkere SS, Ahmed T, Chen Y, Lemacon DS, Li Y, Tang Z, Wadugu BA, Warner WA, Pruett-Miller SM, Obeng EA, Lin DC, He D, Xiao F, Bailis JM, Walter MJ, You Z. Nonsense-mediated RNA Decay Is a Unique Vulnerability of Cancer Cells Harboring SF3B1 or U2AF1 Mutations. Cancer Research, 2021, 18: 4499-4513. DOI: 10.1158/0008-5472.CAN-20-4016
Li S, Lavagnino Z, Lemacon D, Kong L, Ustione A, Ng X, Zhang Y, Wang Y, Zheng B, Piwnica-Worms H, Vindigni A, Piston DW and You Z. Ca2+-stimulated AMPK-dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection. Molecular Cell, 2019, 74: 1123-1137. DOI: 10.1016/j.molcel.2019.04.003
Paudyal SC, Li S, Yan H, Hunter T and You Z. Dna2 Initiates Resection at Clean DNA Double-strand Breaks. Nucleic Acids Research, 2017, 45(20): 11766-11781. DOI: 10.1093/nar/gkx830
Nickless A, Cheruiyot A, Flanagan K, Piwnica-Worms, D, Stewart S and You Z. p38 MAPK Inhibits Nonsense-mediated RNA Decay in Response to Persistent DNA Damage in Non-cycling Cells. Journal of Biological Chemistry, 2017, 292: 15266-15276. DOI: 10.1074/jbc.M117.787846
Nickless A, Jackson E, Marasa J, Nugent P, Mercer RW, Piwnica-Worms D# and You Z#. Intracellular Calcium Regulates Nonsense-mediated mRNA Decay. Nature Medicine, 2014, 20: 961-966. DOI: 10.1038/nm.3620
Chen X, Paudyal SC, Chin RI, You Z. PCNA Promotes Processive DNA End Resection by Exo1. Nucleic Acids Research, 2013, 41: 9325-9338. DOI: 10.1093/nar/gkt672
You Z, Shi L, Zhu Q, Wu P, Zhang Y, Basilio A, Tonnu N, Verma I, Berns M and Hunter T#. CtIP Links DNA Double-strand Break Sensing to Resection. Molecular Cell, 2009, 36: 954-969. DOI: 10.1016/j.molcel.2009.12.002
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