本课题组聚焦RNA解码与创新治疗的总体方向，深度融合多模态人工智能与RNA基础生物学，系统解析RNA动态结构与转录后调控的底层密码。我们致力于打通从新靶点发现、小核酸药物智能设计到肿瘤类器官验证的全链条，以前沿交叉科学驱动精准靶向药物的研发与转化。

1. RNA结构调控机制与多模态AI建模

聚焦RNA动态结构对功能调控的分子机制，结合高通量筛选技术构建RNA-分子互作数据体系，发展融合序列、结构与化学信息的多模态人工智能模型。系统解析RNA结构-分子识别-生物效应之间的传递规律，建立RNA成药性预测与分子设计方法，并在细胞与类器官模型中开展功能验证。

2.RNA靶向药物的智能设计与计算平台

面向siRNA、ASO等小核酸药物设计中的靶点可及性与脱靶问题，构建基于多模态数据的智能设计方法。整合RNA序列、结构及修饰信息，建立活性与特异性联合预测模型，开发从靶点输入到候选分子生成与评价的一体化设计平台，提升核酸药物研发效率与可重复性。

3.RNA编辑选择性调控机制及肿瘤功能研究

围绕RNA编辑酶ADAR的选择性调控机制，重点解析双链RNA结构对编辑效率与位点特异性的决定作用。构建结构驱动的预测模型与功能筛选体系，实现对致病性编辑事件的精准调控，并在结直肠癌模型中系统评估其生物学功能与治疗潜力。

4.ADAR1与线粒体dsRNA介导的肿瘤免疫调控机制

研究ADAR1在调控线粒体来源免疫原性dsRNA稳态中的作用，解析其在肿瘤代谢与免疫信号耦联中的分子机制。结合线粒体功能、氧化还原状态（ROS）及先天免疫通路（如MDA5），阐明RNA编辑调控内源性免疫激活的新机制，并探索其在肿瘤免疫干预中的应用潜力。

2022年，上海市领军人才项目（海外）

2024年，青年百人计划启动基金

2025年，同济大学附属普陀区人民医院柔性引进人才基金

2025年，上海市自然基金面上项目

2025年，重点新材料研发及应用国家科技重大专项

2026年，同济大学“医学+X”交叉研究项目培育项目

1. Wang W, Qi C, Lv K, Liu Y, Li D, Li X, Yu J, Liu Y, Zhang L, Song Y#, Luo K# and Du S#. First-principles study on magnetic MXenes for free radical trapping and sensing. Journal of Materials Chemistry C. 2026;d6tc00069j.# Co-corresponding author.

2. Liu Y, Liang H, Yu J#, Liu Y, Song Y#, Mouham Y, Zhang L, Shiyu Du S#, A DFT study for α-phase uranium and uranium-zirconium alloys in low concentration: Stability, electronic structure, elastic properties and fission gas diffusion. Journal of Nuclear Materials. 2026; 628,156622. # Co-corresponding author.

3. Han J*, SongY*, Xie J, Shen H, Gan WL, Ng L, Ng BYL, Ng VHE, Sui X, Tano V, Tang SJ,Chen L. Modulation of m6A RNA modification by DAP3 in cancer cells. Proceedingsof the National Academy of Sciences of the United States of America. 2024Oct;121(40):e2404509121. *Co-first author.

4.  Song Y, An O, Ren X,Chan TH, Tay DJ, Tang SJ, Han J, Hong HQ, Ng VHE, Ke X, Shen H, Pitcheshwar P,Lin SJ, Leong KW, Molias FB, Yang H, Kappei D, Chen L. RNA editing mediates thefunctional switch of COPA in a novelmechanism of hepatocarcinogenesis. Journal of Hepatology. 2021 Jan;74(1):135-147.

5. Song Y#,*, Ke X*,Chen L#. Potential use of RNA-based therapeutics for breast cancertreatment. Current Medicinal Chemistry. 2021;28(25):5110-5136. *Co-first author, # Co-corresponding author.

6. Qi L*, Song Y*, Chan TH, Lin CH, Yang H, HongHQ, Tay DJT, Lin JS, Maury JJP, Tenen DG, Chen L. An RNA editing/dsRNAbinding-independent gene regulatory mechanism of ADARs and its clinicalimplication in cancer. Nucleic Acids Research. 2017 Oct13;45(18):10436-10451. *Co-first author.

7. Song Y, Chen L, Zeng T,Chan TH, Lian QZ, Chow R, Cai X, Li Y, Li Y, Liu M, Wong N, Yuan YF, Pei D,Guan XY. Loss of ATOH8 Increases StemCell Features of Hepatocellular Carcinoma Cells. Gastroenterology, 2015Oct;149(4):1068-81.e5.

8.  Gan WL, Ren X, Ng VHE, Song Y, Tano V, Han J,Ng L, An O, Xie J, BLY, Tay DJT, Tang SJ, Shen H, Khare S, Young DY, DasGuptaR, Chen L. Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulatesADAR1-mediated immunity in the liver. Cell Reports. 2024 Jul 23;43(7):114400.

9. Guo J, Chen S, Onishi Y, Shi Q, Song Y, Mei H,Chen L, Kool ET, Zhu RY. RNA Control via Redox-Responsive Acylation. AngewChem Int Ed Engl. 2024 May 21;63(21):e202402178.

10. Guo M, Chan HMT, Zhou QL, An O, Li Y, Song Y,Tan ZH, Ng HEV, Peramangalam PS, Tan ZQ, Cao X, Iwanaga E, Matsuoka M, Ooi MG,Jen WY, Koh LP, Chan E, Tan LK, Goh Y, Wang W, Koh BTH, Chan MC, Fullwood MJ,Chng WJ, Osato M, Pulikkan JA, Yang H, Chen L, Tenen DG. Core binding factorfusion downregulation of ADAR2 RNA editing contributes to AML leukemogenesis.Blood. 2023 Jun 22;141(25):3078-3090

11. Han J, An O, Ren X, Song Y, Tang SJ, Shen H,  KeXY, Ng VHE, Tay DJ, Tan HQ, Kappei D, Yang H, Chen L. Multilayered Control ofSplicing Regulatory Networks by DAP3 Leads to Widespread Alternative SplicingChanges in Cancer. Nature Communications. 2022 Apr 4;13(1):1793.

12. Shen H, An O n, Ren X, Song Y, Tang SJ, Ke XY, Han J, Tay DJ, Ng VHE, Molias FB,Pitcheshwar P, Leong KW, Tan KK, Yang H, Chen L. ADARs act as potent regulatorsof circular transcriptome in cancer. Nature Communications. 2022 Mar21;13(1):1508.

13. Molias FB, Sim A, Leong KW, An O, Song Y, Ng VHE, Lim MWJ, Ying C, TeoJXJ, Göke J, Chen L. Antisense RNAs influence promoter usage of theircounterpart sense genes in cancer. Cancer Research. 2021 Dec1;81(23):5849-5861.

14. Tay DJ, Song Y,Peng B, Toh TB, Hooi L, Kaixin Toh DF, Hong H, Tang SJ, Han J, Gan WL, Man ChanTH, Krishna MS, Patil KM, Maraswami M, Loh TP, Dan YY, Zhou L, Bonney GK,Kah-Hoe Chow P, Chen G, Kai-Hua Chow E, Le MT, Chen L. Targeting RNA Editing ofAntizyme Inhibitor 1: a Potential Oligonucleotide-Based Antisense Therapy forCancer. Molecular Therapy. 2021 Nov 3;29(11):3258-3273.

15. An O, Song Y,Ke X, So J, Sundar R, Yang H, Rha SY, Lee MH, Tay ST, Ong X, Keng ATL, Ng M,Tantoso E, Chen L, Tan P, and Yong WP. "3G" Trial: An RNA EditingSignature to Guide Gastric Cancer Chemotherapy. Cancer Research. 2021 May15;81(10):2788-2798.

16. Han J, An O, Hong H, Chan TH, Song Y, Shen H, Tang SJ, Lin JS, Ng VHE, Tay DJ, Molias FB,Pitcheshwar P, Yang H, Chen L. Suppression of Adenosine-to-Inosine (A-to-I) RNAEditome by Death Associated Protein 3 (DAP3) Promotes Cancer Progression. ScienceAdvances, 2020 Jun 17;6(25):eaba5136.

17. Tang SJ, Shen H, An O, Hong HQ, Li J, Song Y, Han J, Tay DJ, Ng VHE, MoliasFB, Leong KW, Pitcheshwar P, Yang H, Chen L. Cis- andtrans-regulations of pre-mRNA splicing by RNA editing enzymes influence cancerdevelopment. Nature Communications. 2020 Feb 7;11(1):799.

18. Hong HQ, An O, Chan TH, Ng VHE, Kwok HS, Lin JS, QiL, Han J, Tay DJT, Tang SJ, Yang H, Song Y,Molias FB, Tenen DG and Chen L. Bidirectional regulation ofadenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) incancer. Nucleic Acids Research, 2018 Sep 6;46(15):7953-7969.

19. Chan TH, Qamra A, Tan KT, Guo J, Yang H, Qi L, LinJS, Ng VH, Song Y, Hong H, Tay ST,Liu Y, Lee J, Rha SY, Feng Z, So JB, Bin Tean T, Guan YK, Rozen S, Tenen DG,Tan P, Chen L. ADAR-mediated RNA editing predicts progression and prognosis ofGastric Cancer. Gastroenterology.2016 Oct;151(4):637-650.e10.

20. Liu M, Chen L, Ma N, Chow R, Li Y, Song Y, Chan THM, Fang S, Yang X, Xi S,Jiang L, Li Y, Zeng T, Li Y, Yuan Y, and Guan XY. CHD1L Promotes LineageReversion of Hepatocellular Carcinoma through Opening Chromatin for KeyDevelopmental Transcription Factors. Hepatology；2016 May;63(5):1544-59.

21. Chow RK, Sin ST, Liu M, Li Y, Chan TH, Song Y, Chen L, Kwong DL, Guan XY. AKR7A3suppresses tumorigenicity and chemoresistance in hepatocellular carcinomathrough attenuation of ERK, c-Jun and NF-κB signaling pathways. Oncotarget. 2016 Oct 18; 8(48):83469-83479

22. Liu M, Li Y, Chen L, Chan TH, Song Y, Fu L, Zeng T, Dai YD, Zhu YH, Li Y, Chen J, Yuan YF, GuanXY. Allele-specific imbalance of Oxidative Stress Induced Growth Inhibitor 1contributes to the progression of hepatocellular carcinoma. Gastroenterology. 2014 Apr;146(4):1084-96.

23. Chan TH, Lin CH, Qi L, Fei J, Li Y, Yong KJ, Liu M, Song Y, Chow RK, Ng VH, Yuan YF, TenenDG, Guan XY, Chen L. A disrupted RNA editing balance mediated by ADARs(Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Gut. 2013 May;63(5):832-43.

24. Chen L, Li Y, Lin CH, Chan TH, Chow RK, Song Y, Liu M, Yuan YF, Fu L, Kong KL,Qi L, Li Y, Zhang N, Tong AH, Kwong DL, Man K, Lo CM, Lok S, Tenen DG, Guan XY.Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. NatureMedicine. 2013Feb;19(2):209-16.

25. Fan H, Chen L, Zhang F, Quan Y, Su X, Qiu X, Zhao Z,Kong KL, Dong S, Song Y, Chan TH,Guan XY. MTSS1, a novel target of DNA methyltransferase 3B, functions as atumor suppressor in hepatocellular carcinoma. Oncogene. 2012 May 3;31(18):2298-308.