丁胜
电子邮件：shengding@tsinghua.edu.cn
电话：+86-10-62795022
研究方向：
丁胜教授实验室一直致力于开发全新的化学方法，并用于干细胞与再生医学的研究，以期发现和鉴定可以调控细胞命运和功能（例如，不同发育阶段及不同组织中干细胞的维持、激活、分化和重编程）的全新小分子化合物。具体研究内容包括：（1）揭示干细胞自我更新和多能性的机理；（2）诱导胚胎干细胞向不同谱系（例如，神经、心脏、胰腺等）的分化；（3）人组织特异性干细胞和祖细胞的定向分化；（4）研究细胞的可塑性和重编程过程（例如，生成iPS细胞、转分化等）；（5）扩增无分裂能力的成体细胞（例如，心肌细胞、胰腺b细胞等）；（6）解析参与胚胎发育的信号通路（例如，Wnt、Hh、BMP、FGF等）以及表观遗传学（组蛋白和DNA的甲基化与去甲基化）的分子机制；（7）为药物研发提供技术支持。此外，丁胜教授研究团队针对所发现的小分子化合物开展了大量的工作，通过全面的构效关系分析、亲和层析鉴定靶标、转录组学分析、蛋白质组学分析、化学/遗传上位分析，以及体外、体内生化和功能分析，对其分子机制进行研究。到目前为止，很多功能小分子化合物及其作用机制已经或正在被确定，它们能够通过上述生物学过程之一对干/祖细胞进行调节。这些研究将最终推动干细胞的治疗性应用，以及帮助开发能够用于体内组织、器官再生或癌症治疗的小分子药物。
代表性科研论文
1.Hu X, Wu J, Shi L, Wang F, He K, Tan P, Hu Y, Yang Y, Wang D, Ma T, Ding S. (2025). The transcription factor MEF2C restrains microglial overactivation by inhibiting kinase CDK2. Immunity. 58(4): 946-960
2.He K, Xue Q, Zhou W, Wang P, Hu X, Lin T, Chen N, Wang B, Ma T, Ding S. (2024). Extended pegRNAs enhance the editing capability of Prime editing. Trends Biotechnol. 43(1): 206-219
3.Zhou W, He K, Wang C, Wang P, Wang D, Wang B, Geng H, Lian H, Ma T, Nie Y, Ding S. (2023). Pharmacologically inducing regenerative cardiac cells by small molecule drugs. eLife. 13:RP93405.
4.Hu Y, Yang Y, Tan P, Zhang Y, Han M, Yu J, Zhang X, Jia Z, Wang D, Li Y, Ma T, Liu K, Ding S. (2022). Induction of mouse totipotent stem cells by a defined chemical cocktail. Nature. 617(7962): 792-797
5.Li Y, Wang C, Gao H, Gu J, Zhang Y, Zhang Y, Xie M, Cheng X, Yang M, Zhang W, Li Y, He M, Xu H, Zhang H, Ji Q, Ma T, Ding S, Zhao Y, Gao Y. (2022). KDM4 inhibitor SD49-7 attenuates leukemia stem cell via KDM4A/MDM2/p21CIP1 axis. Theranostics 12(11):4922-4934
6.Desai RV, Chen X, Martin B, Chaturvedi S, Hwang DW, Li W, Yu C, Ding S, Thomson M, Singer RH, Coleman RA, Hansen MMK, Weinberger LS. (2021). A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions. Science. 373(6557): eabc6506
7.Zhou W, Ma T, Ding S. (2021). Non-viral approaches for somatic cell reprogramming into cardiomyocytes. Semin Cell Dev Biol. 122: 28-36
8.Theodoris CV, Zhou P, Liu L, Zhang Y, Nishino T, Huang Y, Kostina A, Ranade SS, Gifford CA, Uspenskiy V, Malashicheva A, Ding S, Srivastava D. (2021). Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease. Science. 371(6530): eabd0724
9.Lu G, Zhang X, Zheng W, Sun J, Hua L, Xu L, Chu XJ, Ding S, Xiong W. (2020). Development of a simple in vitro assay to identify and evaluate nucleotide analogs against SARS-CoV-2 RNA-dependent RNA polymerase. Antimicrob Agents Chemother. 65(1): e01508-20
10.Yu C, Ding S. (2020). Therapeutic strategies targeting somatic stem cells: Chemical approaches. Bioorg Med Chem. 28(24):115824
11.Telpoukhovskaia MA, Liu K, Sayed FA, Etchegaray JI, Xie M, Zhan L, Li Y, Zhou Y, Le D, Bahr BA, Bogyo M, Ding S, Gan L. (2020). Discovery of small molecules that normalize the transcriptome and enhance cysteine cathepsin activity in progranulin-deficient microglia. Sci Rep. 10(1):13688
12.Wilson JL, Cheung KWK, Lin L, Green EAE, Porrás AI, Zou L, Mukanga D, Akpa PA, Darko DM, Yuan R, Ding S, Johnson WCN, Lee HA, Cooke E, Peck CC, Kern SE, Hartman D, Hayashi Y, Marks PW, Altman RB, Lumpkin MM, Giacomini KM, Blaschke TF. (2020). Scientific considerations for global drug development. Sci Transl Med. 12(554): eaax2550
13.Perry JM, Tao F, Roy A, Lin T, He XC, Chen S, Lu X, Nemechek J, Ruan L, Yu X, Dukes D, Moran A, Pace J, Schroeder K, Zhao M, Venkatraman A, Qian P, Li Z, Hembree M, Paulson A, He Z, Xu D, Tran TH, Deshmukh P, Nguyen CT, Kasi RM, Ryan R, Broward M, Ding S, Guest E, August K, Gamis AS, Godwin A, Sittampalam GS, Weir SJ, Li L. (2020). Overcoming Wnt-β-catenin dependent anticancer therapy resistance in leukaemia stem cells. Nat Cell Biol. 22(6): 689-700
14.An Z, Liu P, Zheng J, Si C, Li T, Chen Y, Ma T, Zhang MQ, Zhou Q, Ding S. (2019). Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4. Cell Rep. 29(7): 1986-2000
15.Liu C, Hu X, Li Y, Lu W, Li W, Cao N, Zhu S, Cheng J, Ding S, Zhang M. (2019). Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach. J Mol Cell Biol. 11(6): 489-495
16.Li F, Xu Y, Liu B, Singh PK, Zhao W, Jin J, Han G, Scott AW, Dong X, Huo L, Ma L, Pizzi MP, Wang Y, Li Y, Harada K, Xie M, Skinner HD, Ding S, Wang L, Krishnan S, Johnson RL, Song S, Ajani JA. (2019). YAP1-Mediated CDK6 Activation Confers Radiation Resistance in Esophageal Cancer - Rationale for the Combination of YAP1 and CDK4/6 Inhibitors in Esophageal Cancer. Clin Cancer Res. 25(7): 2264-2277
