丁秋蓉

丁秋蓉

丁秋蓉,女,博士研究員博士生導師中科院營養代謝與食品安全重點實驗室多能幹細胞與肝臟疾病課題組組長。

基本介紹

  • 中文名:丁秋蓉
  • 畢業院校:南京大學
  • 就職單位:中國科學院上海營養與健康研究院
  • 職稱:研究員
人物經歷,研究方向,代表性論文,

人物經歷

2010-2014年:美國哈佛大學幹細胞研究所、幹細胞與轉化生物學系 博士後
2004-2010年:中國科學院上海生命科學研究院營養科學研究所 博士
2000-2004年:南京大學生物科學系 學士

研究方向

1. 基於人多能幹細胞的疾病研究和靶向治療
利用患者來源的誘導性多能幹細胞(iPSC)或者體外建立的疾病胚胎幹細胞(ESC),結合基因編輯和定向分化平台,在功能基因組水平研究人類肝臟疾病的分子機理,發現新型靶標;發展基於幹細胞疾病模型的藥物篩選和毒理評價體系;進行藥物化合物篩選,研發針對特定靶標的藥物先導化合物;最佳化體外多能幹細胞肝向分化平台,建立肝臟異種嵌合動物模型,探索基於人多能幹細胞來源的肝臟細胞作為肝移植潛在肝源的可行性。
2. 肝臟脂代謝紊亂的遺傳及表觀遺傳基礎
結合幹細胞疾病模型、基因編輯在體大規模篩選和人群疾病遺傳學分析,研究肝臟脂代謝紊亂及其導致的肝再生能力下降的遺傳和表觀遺傳基礎,探索預防和治療包括脂肪肝、肝纖維化等肝病的方法和手段。
3. 代謝疾病的基因治療研究
針對高甘油三酯血症、高膽固醇血症、腫瘤惡病質等代謝疾病,以CRISPR/Cas9在體靶向技術為基礎,篩選新型靶標,最佳化基因治療方案,開展臨床前研究。

代表性論文

* 通訊作者
  1. 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*. (2020) MRG15 orchestrates rhythmic epigenomic remodeling and controls hepatic metabolism. Nat Metab May;2(5):447-460
  2. Yang Y, Liu X, Li S, Chen Y, Zhao Y, Wei Y, Qiu Y, Liu Y, Zhou Z, Han J*, Wu G*, Ding Q*. (2020) Genome-scale CRISPR screening for potential targets of ginsenoside compound K. Cell Death Dis Jan 20;11(1):39
  3. Zhao H, Li Y, He L, Pu W, Yu W, Li Y, Wu YT, Xu C, Wei Y, Ding Q, Song BL, Huang H, Zhou B. (2020) In Vivo AAV-CRISPR/Cas9-Mediated Gene Editing Ameliorates Atherosclerosis in Familial Hypercholesterolemia. Circulation 141(1):67-79
  4. Zhao Y, Feng Z, Ding Q*. (2019) Type 2 Diabetes Variants in the SLC16A11 coding region are not loss-of-function mutations. Cell Reports 29(3):781-784
  5. Li S, Huang S, Zhao Y, Ding Y, Ma D, Ding Q*. (2019) Derivation and applications of human hepatocyte-like cells. World J Stem Cells 11(8):535-547
  6. Zhang X, Zhang H, Xu C, Li X, Li M, Wu X, Pu W, Zhou B, Wang H, Li D, Ding Q, Ying H, Wang H, Zhang H. (2019) Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis. Nat Commun 10(1):4158
  7. 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
  8. Zhao G, Gong L, Su D, Jin Y, Guo C, Yue M, Yao S, Qin Z, Ye Y, Tang Y, Wu Q, Zhang J, Cui B, Ding Q, Huang H, Hu L, Chen Y, Zhang P, Hu G, Chen L, Wong KK, Gao D, Ji H. (2019) Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1. J Clin Invest 129:972-987
  9. Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, Yu S, Li X, Zhang H, Qian H, Zhang D, Guo F, Zhai Q, Ding Q, Wang L, Ying H. (2018) microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A 115(46):E10849-E10858
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. Small KS, Todorcevic 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, Vinuela 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
  16. 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
  17. 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
  18. Sun Y, Ding Q*. (2017) Genome engineering of stem cell organoids for disease modeling. Protein Cell 8(5):315-327
  19. 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
  20. Deng HX, Wang Y, Ding QR, Li DL, Wei YQ. (2017) Gene therapy research in Asia. Gene Ther 24(9):572-577
  21. 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
  22. 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
  23. 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
  24. Han J, Xi Q, Meng Q, Liu J, Zhang Y, Han Y, Zhuang Q, Jiang Y, Ding Q, Wu G (2016). Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer. Oncol Lett 12(6):4665-4670
  25. Han J, Meng Q, Xi Q, Zhang Y, Zhuang Q, Han Y, Jiang Y, Ding Q, Wu G (2016). Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer. Int J Oncol 48(1):215-224
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. Ding Q, Cowan CA. (2013) Liver in a dish. Cell Res 23(11):1242-1243
  34. 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
  35. 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)
  36. Luo X, Ding Q, Wang M, Li Z, Mao K, Sun B, Zang YQ, 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)

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