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丁秋蓉

丁秋蓉

博士
多能干细胞与肝脏疾病研究组组长

邮箱: qrding@sinh.ac.cn

电话: +86-21-54920998

所属部门: 中国科学院营养代谢与食品安全重点实验室

个人简历

2017-至   今：中国科学院上海营养与健康研究所 研究员
2014-2016年：中国科学院上海生命科学研究院营养科学研究所 研究员
2010-2014年：美国哈佛大学干细胞研究所、干细胞与转化生物学系 博士后
2004-2010年：中国科学院上海生命科学研究院营养科学研究所 博士
2000-2004年：南京大学生物科学系 学士
　　

研究方向

多能干细胞与肝脏疾病

研究内容

1. 基于人多能干细胞的疾病研究和靶向治疗
    利用患者来源的诱导性多能干细胞（iPSC）或者体外建立的疾病胚胎干细胞（ESC），结合基因编辑和定向分化平台，在功能基因组水平研究人类肝脏疾病的分子机理，发现新型靶标；发展基于干细胞疾病模型的药物筛选和毒理评价体系；进行药物化合物筛选，研发针对特定靶标的药物先导化合物；优化体外多能干细胞肝向分化平台，建立肝脏异种嵌合动物模型，探索基于人多能干细胞来源的肝脏细胞作为肝移植潜在肝源的可行性。
2. 肝脏脂代谢紊乱的遗传及表观遗传基础
    结合干细胞疾病模型、基因编辑在体大规模筛选和人群疾病遗传学分析，研究肝脏脂代谢紊乱及其导致的肝再生能力下降的遗传和表观遗传基础，探索预防和治疗包括脂肪肝、肝纤维化等肝病的方法和手段。
3. 代谢疾病的基因治疗研究
    针对高甘油三酯血症、高胆固醇血症、肿瘤恶病质等代谢疾病，以CRISPR/Cas9在体靶向技术为基础，筛选新型靶标，优化基因治疗方案，开展临床前研究。　　

代表论著（#第一作者，*通讯作者）

  1. Zhao Y#*, Li S#, Chen Y, Wang Y, Wei Y, Zhou T, Zhang Y, Yang Y, Chen L, Liu Y, Hu C, Zhou B, Ding Q*. Histone phosphorylation integrates the hepatic glucagon-PKA-CREB gluconeogenesis program in response to fasting. Mol Cell 2023 Apr 6;83(7):1093-1108
  2. Chen Y#*, Chen L#, Wu X#, Zhao Y, Wang Y, Jiang D, Liu X, Zhou T, Li S, Wei Y, Liu Y, Hu C, Zhou B, Qin J, Ying H, Ding Q*. Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice. Nat Commun 2023 Mar 18;14(1):1521
  3. Wu X, Jiang D, Li S*, Ding Q*. Modeling drug-induced liver injury and screening for anti-hepatofibrotic compounds using human PSC-derived organoids. Cell Regen 2023 Mar 3;12(1):6
  4. Tian C, Min X, Zhao Y, Wang Y, Wu X, Liu S, Dou W, Zhou T, Liu Y, Luo R, Li Z, Lui KO, Li Y, Zhou B, Ding Q*. MRG15 aggravates non-alcoholic steaohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM. J Hepatol 2022 Dec;77(6):1491-1503
  5. Zhou T, Musunuru K, Lui K*, Ding Q*. Decoding liver fibrogenesis with single-cell technologies. Life Med 2022 Dec;1(3):333-344
  6. Han J#*, Wang Y#*, Qiu Y, Sun D, Liu Y, Li Z, Zhou B, Zhang H, Xiao Y, Wu G*, Ding Q*. Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting. Cell Disc 2022 Nov 15;8(1):122
  7. Chen Y, Ding Q*. Optimized protocols for efficient gene editing in mouse hepatocytes in vivo using CRISPR-Cas9 technology. STAR Protoc 2021 Dec 23;3(1):101062
  8. Qiu Y, Liu X, Sun Y, Zeng X, Li S, Wei Y, Tian C, Ding Q*. In situ saturating mutagenesis screening identifies a functional genomic locus that regulates Ucp1 expression. Phenomics 2021 Feb 22;1(1):15-21
  9. Qiu Y, Ding Q*. Optimized protocol for gene editing in adipocytes using CRISPR-Cas9 technology. STAR Protoc 2021 Jan 27;2(1):100307
  10. Liu X, Yang Y, Qiu Y, Md Reyad-Ul-Ferdous, Ding Q*, Wang Y*. SeqCor: correct the effect of gRNA sequences in CRISPR/Cas9 screenings by machine learning algorithm. J Genet Genomics 2020 Nov 20;47(11):672-680
  11. Qiu Y, Yang Y, Wei Y, Liu X, Feng Z, Zeng X, Chen Y, Liu Y, Zhao Y, Chen L, Luo L, Ding Q*. Glyburide regulates UCP1 expression in adipocytes independent of K ATP channel blockade. iScience 2020 Aug 10;23(9):101446
  12. Ding Q*. Spotlight on gene therapy in China. Gene Ther 2020 Aug;27(7-8):307-308
  13. Wei Y#, Tian C#, Zhao Y#, Liu X, Liu F, Li S, Chen Y, Qiu Y, Feng Z, Chen L, Zhou T, Ren X, Feng C, Liu Y, Yu W, Ying H, Ding Q*. MRG15 orchestrates rhythmic epigenomic remodeling and controls hepatic metabolism. Nat Metab 2020 May;2(5):447-460
  14. Yang Y#, Liu X#, Li S, Chen Y, Zhao Y, Wei Y, Qiu Y, Liu Y, Zhou Z, Han J*, Wu G*, Ding Q*. Genome-scale CRISPR screening for potential targets of ginsenoside compound K. Cell Death Dis 2020 Jan 20;11(1):39
  15. Zhao Y#, Feng Z#, Ding Q*. Type 2 Diabetes Variants in the SLC16A11 coding region are not loss-of-function mutations. Cell Rep 2019 Oct 15;29(3):781-784
  16. Li S, Huang S, Zhao Y, Ding Y, Ma D, Ding Q*. Derivation and applications of human hepatocyte-like cells. World J Stem Cells 2019 Aug 26;11(8):535-547
  17. Feng Z, Wei Y, Zhang Y, Qiu Y, Liu X, Su L, Liang N, Yin H, Ding Q*. Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression. Theranostics 2019 May 26;9(12):3501-3514
  18. Zhao Y#, Feng Z#, Zhang Y#, Sun Y, Chen Y, Liu X, Li S, Zhou T, Chen L, Wei Y, Ma D, Lui K, Ying H, Chen Y, Ding Q*. Gain-of-function mutations of SLC16A11 contribute to the pathogenesis of type 2 diabetes. Cell Rep 2019 Jan 22;26(4):884-892
  19. Qiu Y#, Sun Y#, Xu D, Yang Y, Liu X, Wei Y, Chen Y, Feng Z, Li S, Ferdous M, Zhao Y, Xu H, Lao Y*, Ding Q*. Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue. EBioMedicine 2018 Nov;37:344-355
  20. Li S, Li M, Liu X, Yang Y, Wei Y, Chen Y, Qiu Y, Zhou T, Feng Z, Ma D, Fang J, Ying H, Wang H, Musunuru K, Shao S*, Zhao Y*, Ding Q*. Genetic and chemical screenings identify HDAC3 as a key regulator in hepatic differentiation of human pluripotent stem cells. Stem Cell Rep 2018 Jul 10;11(1):22-31
  21. Sun Y, Ding Q*. Genome engineering of stem cell organoids for disease modeling. Protein Cell 2017 May;8(5):315-327
  22. Wei Y, Qiu Y, Chen Y, Liu G, Zhang Y, Xu L, Ding Q*. CRISPR/Cas9 with single guide RNA expression driven by small tRNA promoters showed reduced editing efficiency compared to U6 promoter. RNA 2017 Jan;23(1):1-5
  23. Wei Y, Chen Y, Qiu Y, Zhao H, Liu G, Zhang Y, Meng Q, Wu G, Chen Y, Cai X, Wang H, Ying H, Zhou B, Liu M, Li D, Ding Q*. Prevention of muscle wasting by CRISPR/Cas9-mediated disruption of myostatin in vivo. Mol Ther 2016 Nov;24(11):1889-1891
  24. Chen Y, Liu X, Zhang Y, Wang H, Ying H, Liu M, Li D, Lui K, Ding Q*. A Self-restricted CRISPR System to Reduce Off-target Effects. Mol Ther 2016 Sep;24(9):1508-1510
  25. Wang X, Raghavan A, Chen T, Qiao L, Zhang Y, Ding Q*, Musunuru K*. CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo-Brief Report. Arterioscler Thromb Vasc Biol 2016 May;36(5):783-786
  26. Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Rader DJ, Musunuru K. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 2014 Aug 15;115(5):488-492
  27. Ding Q, Regan SN, Xia Y, Oostrom LA, Cowan CA, Musunuru K. Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 2013 Apr 4;12(4):393-394
  28. Ding Q#, Lee YK#, Schaefer EA#, Peters DT, Veres A, Kim K, Kuperwasser N, Motola DL, Meissner TB, Hendriks WT, Trevisan M, Gupta RM, Moisan A, Banks E, Friesen M, Schinzel RT, Xia F, Tang A, Xia Y, Figueroa E, Wann A, Ahfeldt T, Daheron L, Zhang F, Rubin LL, Peng LF, Chung RT, Musunuru K, Cowan CA. A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 2013 Feb 7;12(2):238-251 (#equal contribution)
  29. Ding Q, Cowan CA. Liver in a dish. Cell Res 2013 Nov;23(11):1242-1243
  30. Jin T#, Ding Q#, Huang H, Xu D, Jiang Y, Zhou B, Li Z, Jiang X, He J, Liu W, Zhang Y, Pan Y, Wang Z, Thomas WG, Chen Y. PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Res 2012 Apr;22(4):661-676 (#equal contribution)
  31. Luo X#, Ding Q#, Wang M#, Li Z, Mao K, Sun B, Zang YQ, Chen Y. In vivo disruption of TGF-β signaling by Smad7 in airway epithelium alleviates allergic asthma but aggravates lung carcinogenesis. PLoS ONE 2010 Apr 13;5(4):e10149 (#equal contribution)
  32. Ding Q, Wang Z, Chen Y. Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway. Cell Res 2009 Mar;19(3):317-327
  33. Ding Q, Jin T, Wang Z, Chen Y. Catalase potentiates retinoic acid-induced THP-1 monocyte differentiation into macrophage through inhibition of peroxisome proliferator-activated receptor gamma. J Leukoc Biol 2007 Jun;81(6):1568-1576
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