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丁秋蓉

丁秋蓉

博士
多能干細(xì)胞與肝臟疾病研究組組長(zhǎng)

郵箱: qrding@sinh.ac.cn

電話: +86-21-54920998

所屬部門: 中國(guó)科學(xué)院營(yíng)養(yǎng)代謝與食品安全重點(diǎn)實(shí)驗(yàn)室

個(gè)人簡(jiǎn)歷

2017-至???今：中國(guó)科學(xué)院上海營(yíng)養(yǎng)與健康研究所 研究員
2014-2016年：中國(guó)科學(xué)院上海生命科學(xué)研究院營(yíng)養(yǎng)科學(xué)研究所 研究員
2010-2014年：美國(guó)哈佛大學(xué)干細(xì)胞研究所、干細(xì)胞與轉(zhuǎn)化生物學(xué)系 博士后
2004-2010年：中國(guó)科學(xué)院上海生命科學(xué)研究院營(yíng)養(yǎng)科學(xué)研究所 博士
2000-2004年：南京大學(xué)生物科學(xué)系 學(xué)士
　　

研究方向

多能干細(xì)胞與肝臟疾病

研究?jī)?nèi)容

1. 基于人多能干細(xì)胞的疾病研究和靶向治療
????利用患者來(lái)源的誘導(dǎo)性多能干細(xì)胞（iPSC）或者體外建立的疾病胚胎干細(xì)胞（ESC），結(jié)合基因編輯和定向分化平臺(tái)，在功能基因組水平研究人類肝臟疾病的分子機(jī)理，發(fā)現(xiàn)新型靶標(biāo)；發(fā)展基于干細(xì)胞疾病模型的藥物篩選和毒理評(píng)價(jià)體系；進(jìn)行藥物化合物篩選，研發(fā)針對(duì)特定靶標(biāo)的藥物先導(dǎo)化合物；優(yōu)化體外多能干細(xì)胞肝向分化平臺(tái)，建立肝臟異種嵌合動(dòng)物模型，探索基于人多能干細(xì)胞來(lái)源的肝臟細(xì)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(chǔ)
????結(jié)合干細(xì)胞疾病模型、基因編輯在體大規(guī)模篩選和人群疾病遺傳學(xué)分析，研究肝臟脂代謝紊亂及其導(dǎo)致的肝再生能力下降的遺傳和表觀遺傳基礎(chǔ)，探索預(yù)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(duì)高甘油三酯血癥、高膽固醇血癥、腫瘤惡病質(zhì)等代謝疾病，以CRISPR/Cas9在體靶向技術(shù)為基礎(chǔ)，篩選新型靶標(biāo)，優(yōu)化基因治療方案，開(kāi)展臨床前研究。　　

代表論著（#第一作者，*通訊作者）

  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