edf壹定发

全体研究组长

丁秋蓉
博士 研究员 博士生导师

中科院营养代谢与食品安全重点实验室多能干细胞与肝脏疾病课题组组长

研究方向:
1. 基于人多能干细胞的疾病研究和靶向治疗
2. 肝脏脂代谢紊乱的遗传及表观遗传基础
3. 代谢疾病的基因治疗

电子邮件(E-mail):qrding@sibs.ac.cn

电话(Tel):54920998

邮政编码:200031

简历 & 研究方向
2017-至     今:edf壹定发 研究员
2014-2016年:edf壹定发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:edf壹定发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
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。

代表性论文(* 通讯编辑)

  1. Feng Z, Wei Y, Zhang Y, Qiu Y, Liu X, Su L, Liang N, Yin H, Ding Q*. (2019) Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression. Theranostics 9:3501-3514.
  2. Zhao Y, Feng Z, Zhang Y, Sun Y, Chen Y, Liu X, Li S, Zhou T, Chen L, Wei Y, Ma D, Lui Kathy O, Ying H, Chen Y, Ding Q*. (2019) Gain-of-Function Mutations of SLC16A11 Contribute to the Pathogenesis of Type 2 Diabetes. Cell Rep 26:884-892.
  3. 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*. (2018) Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue. EBioMedicine 37:344-355.
  4. Yuan J, Ma Y, Huang T, Chen Y, Peng Y, Li B, Li J, Zhang Y, Song B, Sun X, Ding Q, Song Y, Chang X. (2018) Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase. Mol Cell 72(2):380-394.e7.
  5. Jiang Q, Li K, Lu WJ, Li S, Chen X, Liu XJ, Yuan J, Ding Q, Lan F, Cai SQ. (2018) Identification of small-molecule ion channel modulators in C. elegans channelopathy models. Nat Commun 9(1):3941.
  6. 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*. (2018) Genetic and chemical screenings identify HDAC3 as a key regulator in hepatic differentiation of human pluripotent stem cells. Stem Cell Rep 11(1):22-31.
  7. Small KS, Todor?evi? M, Civelek M, El-Sayed Moustafa JS, Wang X, Simon MM, Fernandez-Tajes J, Mahajan A, Horikoshi M, Hugill A, Glastonbury CA, Quaye L, Neville MJ, Sethi S, Yon M, Pan C, Che N, Vi?uela A, Tsai PC, Nag A, Buil A, Thorleifsson G, Raghavan A, Ding Q, Morris AP, Bell JT, Thorsteinsdottir U, Stefansson K, Laakso M, Dahlman I, Arner P, Gloyn AL, Musunuru K, Lusis AJ, Cox RD, Karpe F, McCarthy MI. (2018) Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition. Nat Genet 50:572-580.
  8. Shao Y, Wang L, Guo N, Wang S, Yang L, Li Y, Wang M, Yin S, Han H, Zeng L, Zhang L, Hui L, Ding Q, Zhang J, Geng H, Liu M, Li D. (2018) Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats. J Bio Chem 293:6883-6892.
  9. Li X, Ba Q, Liu Y, Yue Q, Chen P, Li J, Zhang H, Ying H, Ding Q, Song H, Liu H, Zhang R, Wang H. (2017) Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein. Cell Discov 3:17042.
  10. Sun Y, Ding Q*. (2017) Genome engineering of stem cell organoids for disease modeling. Protein Cell 8(5):315-327.
  11. Wei Y, Qiu Y, Chen Y, Liu G, Zhang Y, Xu L, Ding Q*. (2017) CRISPR/Cas9 with single guide RNA expression driven by small tRNA promoters showed reduced editing efficiency compared to U6 promoter. RNA 23(1):1-5.
  12. Deng HX, Wang Y, Ding QR, Li DL, Wei YQ. (2017) Gene therapy research in Asia. Gene Ther 24(9):572-577.
  13. Huang C, Sun M, Yang Y, Wang F, Ma X, Li J, Wang Y, Ding Q, Ying H, Song H, Wu Y, Jiang Y, Jia X, Ba Q, Wang H. (2017) Titanium dioxide nanoparticles prime a specific activation state of macrophages. Nanotoxicology 11(6):737-750.
  14. Liu Y, Fan C, Zhang Y, Yu X, Wu X, Zhang X, Zhao Q, Zhang H, Xie Q, Li M, Li X, Ding Q, Ying H, Li D, Zhang H. (2017) RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice. Cell Death Differ 24(8):1459-1469.
  15. Zhang YY, Li C, Yao GF, Du LJ, Liu Y, Zheng XJ, Yan S, Sun JY, Liu Y, Liu MZ, Zhang X, Wei G, Tong W, Chen X, Wu Y, Sun S, Liu S, Ding Q, Yu Y, Yin H, Duan SZ. (2017) Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ERα/HGF/Met Pathway. Diabetes 66(6):1535-1547.
  16. 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*. (2016) Prevention of muscle wasting by CRISPR/Cas9-mediated disruption of myostatin in vivo. Mol Ther 24(11):1889-1891.
  17. Chen Y, Liu X, Zhang Y, Wang H, Ying H, Liu M, Li D, Lui K, Ding Q*. (2016) A Self- restricted CRISPR System to Reduce Off- target Effects. Mol Ther 24(9):1508-1510.
  18. Wang X, Raghavan A, Chen T, Qiao L, Zhang Y, Ding Q*, Musunuru K*. (2016) CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo. Arterioscler Thromb Vasc Biol 143(9):1475-1481. (# Co-corresponding)
  19. Veres A, Gosis BS, Ding Q, Collins R, Ragavendran A, Brand H, Erdin S, Talkowski ME, Musunuru K. (2014) Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing. Cell Stem Cell 15(1);27-30.
  20. Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Rader DJ, Musunuru K. (2014) Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 115:488-492.
    # Seleted as "Best of 2014" by Circulation Research and "Top cardiovascular disease research advances in 2014" by American Heart Association
  21. Ding Q, Regan SN, Xia Y, Oostrom LA, Cowan CA, Musunuru K. (2013) Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 12(4):393-394.
  22. 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. (2013) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12(2):238-251 (# equal contribution)
    # Selected as “Best of 2013” by Cell Stem Cell
  23. Ding Q, Cowan CA. (2013) Liver in a dish. Cell Res 23(11):1242-1243.
  24. Strong A, Ding Q, Edmondson AC, Millar JS, Sachs KV, Li X, Kumaravel A, Wang MY, Ai D, Guo L, Alexander ET, Nguyen D, Lund-Katz S, Phillips MC, Morales CR, Tall AR, Kathiresan S, Fisher EA, Musunuru K, Rader DJ. (2012) Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest 122(8):2807-2816.
  25. Zhu L, Wang L, Luo X, Zhang Y, Ding Q, Jiang X, Wang X, Pan Y, Chen Y. (2012) Tollip, an Intracellular Trafficking Protein, is a Novel Modulator of the Transforming Growth Factor-β Signaling Pathway. J Bio Chem 16; 287(47):39653-39663.
  26. Huang H, Jin T, He J, Ding Q, Xu D, Wang L, Zhang Y, Pan Y, Wang Z, Chen Y. (2012) Progesterone and AdipoQ Receptor 11 Links Ras Signaling to Cardiac Development in Zebrafish. Arterioscler Thromb Vasc Biol 32(9):2158-2170.
  27. Jin T, Xu D, Ding Q, Zhang Y, Mao C, Pan Y, Wang Z, Chen Y. (2012) Identification of the topology and functional domains of PAQR10. Biochem J 443(3):643-653.
  28. 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. (2012) PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Res 22(4):661-676. (# equal contribution)
  29. Luo X, Zhang Y, Ruan X, Jiang X, Zhu L, Wang X, Ding Q, Liu W, Pan Y, Wang Z, Chen Y. (2011) Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis. Diabetes 60(5):1435-1445.
  30. Luo X#, Ding Q#, Wang M#, Li Z, Mao K, Sun B, Zang YQ, and Chen Y. (2010) 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)
  31. Qiu Y, Mao T, Zhang Y, Shao M, You J, Ding Q, Chen Y, Wu D, Xie D, Lin X, Gao X, Kaufman RJ, Li W, Liu Y. (2010) A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells. Sci Signal 26;3(106):ra7.
  32. Ding Q, Wang Z, and Chen Y. (2009) Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway. Cell Res 19(3):317-327.
  33. Feng L, Xie X, Ding Q, Luo X, He J, Fan F, Liu W, Wang Z and Chen Y. (2007) Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci USA 104:14348-14353.
  34. Han R, Lai R, Ding Q, Wang Z, Luo X, Zhang Y, Cui G, He J, Liu W and Chen Y. (2007) Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism. Diabetologia 50:1960-1968.
  35. Ding Q, Jin T, Wang Z and Chen Y. (2007) Catalase potentiates retinoic acid-induced THP-1 monocyte differentiation into macrophage through inhibition of peroxisome proliferator-activated receptor gamma. J Leukoc Biol 81:1568-1576.
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