李大力

2004-9至2007-6      湖南师范大学，遗传学，博士

2001-9至2004-6      湖南师范大学，遗传学，硕士

1997-9至2001-6      湖南师范大学，生物科学，学士

2014-7至今        华东师范大学，生命科学学院，研究员

2009-12至2014-6       华东师范大学，生命科学学院，副教授

2007-7至2009-11       华东师范大学，生命科学学院，讲师

2004-11至2007-5       美国德州农工大学，生物科学与生物技术研究所，研究助理

李大力，博士，华东师范大学生命科学学院研究员，基金委“杰出青年基金”获得者。2007年获湖南师范大学遗传学博士学位，博士期间在美国德州农工大学进行联合研究,毕业后受聘于华东师范大学生命科学学院从事教学与科研工作，2009和2014 年先后破格晋升为副教授、研究员。现为上海市调控生物学重点实验室副主任，华东师范大学闵行实验动物中心主任。多年来通过优化创新基因编辑技术，建立世界领先的基因编辑疾病模型构建技术体系，开发精度和活性更高的hyCBE和A&C-BEmax等多种单碱基编辑系统，以血友病和β地中海贫血等单基因血液遗传病为模型，建立了基于基因编辑技术的遗传病基因治疗新策略。迄今，共发表SCI论文90余篇，作为通讯作者在Nature Biotechnology(2篇)，Nature Cell Biology，PNAS，Cell Research（2篇）和Nature Protocols等高水平期刊发表论文32篇，论文单篇最高他引530余次。围绕基因编辑技术和基因治疗方法以第一发明人申请发明专利12项，已授权一项并转化。作为课题组长主持科技部重点研发项目，上海市教委基因编辑与细胞治疗前沿科学基地等重大项目等，2020年国家自然科学基金杰出青年基金，2018年获教育部高等学校科学研究优秀成果奖（自然科学一等奖，排名第二）。

学术兼职：

Nature Biotechnology, Nature Protocols, Cell Research，Stem Cells等杂志审稿人

中国医药生物技术协会基因编辑技术分会第一届委员会常务委员兼秘书长；

中国医药生物技术协会合成生物技术分会第一届委员会常务委员；

中国遗传学会基因组编辑与合成分会委员；

上海市生物工程学会合成生物学专业委员会委员；

中国抗癌协会第一届肿瘤微环境专业委员会委员。

主要研究方向：

遗传疾病是临床治疗的难题，在目前全球已知的约7000余种遗传疾病中，95%以上都没有有效的治疗手段。患者中50%以上是儿童，给家庭和社会带来沉重的负担。基因治疗是攻克遗传病的有效疗法，近年来已有一批基因药物在临床上展现了巨大的潜力。特别是最近几年已有5个遗传病基因治疗产品上市，为广大的患者带来了希望。然而基因治疗技术的开发和应用还面临挑战：1.整合型载体随机整合引起肿瘤的风险；2.非整合型载体会随时间而丢失，长期疗效无法保证；3.基因治疗离不开合适的动物模型，而传统方法构建疾病模型耗时耗力，限制了新疗法的快速开发。近年兴起的基因编辑技术能精确高效地对基因组进行修饰与改造，在疾病治疗方面有望解决现有基因疗法的不足，是最受关注的新技术之一。因此，如何利用和创新基因编辑工具，快速建立适合基因治疗的遗传疾病动物模型，开发临床可行的治疗策略和技术体系，是基因治疗领域的关键。同时新的基因编辑技术也将为农业育种、微生物产品以及药物研发等领域中的遗传改造提供新的高效技术体系。因此本课题组主要围绕如下两个方面开展研究工作：

1.基因编辑技术体系优化与创新

2.基因治疗策略开发与可行性研究

主持课题：

1)  基因编辑与疾病治疗（国家自然科学基金杰出青年基金No. 32025023 2021-2025）

2)  靶向肝脏和眼等器官的在体基因治疗研究（科技部国家重点研发计划“干细胞及转化研究”专项2019YFA0110802 2019-2023，课题组长）

3)  常染色体显性视神经萎缩症相关蛋白OPA3的人源化突变小鼠模型建立及基因编辑治疗研究（国家自然科学基金No.81873685 2019-2022）

4)  构建PAH基因新突变小鼠模型开展苯丙酮尿症基因治疗研究 (国家自然科学基金 No. 81670470 2017-2020)

5)  上海市基因编辑与细胞治疗前沿科学研究基地    (上海市高校创新策源能力提升计划项目，2021-2025)

6)  精准高效基因编辑新技术开发（上海市科委，21CJ1402200, 2021-2024）

7)  自发罕见病动物模型的收集、制备、保存和在基因治疗研究中的应用（上海市科委重点课题，No. 20140900200, 2020-2023）

8)  精确高效基因编辑体系构建（上海市教委科研创新计划重大项目，2019-01-07-00-05-E00054， 2019-2023）

9)  利用基因编辑技术建立并治疗先天性视神经萎缩相关蛋白OPA1的人源化突变小鼠模型研究（上海市科委重点课题，No.18411953500, 2018-2021）

已完成项目：

1)遗传性视神经萎缩大鼠模型构建及基因治疗研究（上海市创新课题，No.14140901600, 2017-2019）

2)重症免疫缺陷型大鼠品系的构建以及基因编辑技术的优化研究 (上海市创新课题 No.14140900300, 2014-2017)

3)七次跨膜受体Lgr4 及其配体家族在卵巢功能维持和雌性不育中的功能研究 (国家自然科学基金No.31371455 2014-2017 )

4)核仁蛋白PAK1IP1 调节核糖体生物合成的功能及机理研究（国家自然科学基金 No.311713182012-2015）

5)青春发育关键基因KiSS1表达调控研究（国家自然科学基金No.30800627 2009-2011 ）

代表论文:

10篇代表论文:   

1.      Wang L, Aschenbrenner D, Zeng Z, Cao X, Mayr D, Mehta M, […] Huang Y*, Li D*, Uhlig HH, Muise AM*. Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.Nat Genet. 2021 Mar 29. doi: 10.1038/s41588-021-00803-4. (Highlighted by News & Views: The sickening consequences of too much SYK signaling. Nat Genet. 2021 Mar 29.

2.      Zhang X, Zhu B, Chen L, Xie L, Yu W, Wang Y, Li L, Yin S, Yang L, Hu H, Han H, Li Y, Wang L, Chen G, Ma X, Geng H, Huang W, Pang X, Yang Z, Wu Y, Siwko S, Kurita R, Nakamura Y, Yang L, Liu M, Li D.*. Dual Base Editor Catalyzes Both Cytosine and Adenine Base Conversions in Human Cells. Nat Biotechnol. 2020 38(7):856-860.（highlighted by Nat Rev Genet. Multitasking for base editors）

3.      Zhang X, Chen L, Zhu B, Wang L, Chen C, Hong M, Huang Y, Li H, Han H, Cai B, Yu W, Yin S, Yang L, Yang Z, Liu M, Zhang Y, Mao Z, Wu Y, Liu M, Li D*. Increasing efficiency and targeting scope of base editors through fusion of a single strand DNA binding protein domain. Nat Cell Biol. 2020 May 11. doi: 10.1038/s41556-020-0518-8. (highlighted by Nat Cell Biol. Base editing goes into hyperdrive.)

4.      Wang L, Li L, Ma Y, Hu H, Li Q, Yang Y, Liu W, Yin S, Li W, Fu B, Kurita R, Nakamura Y, Liu M*, Lai Y*, Li D.*. Reactivation of γ-globin Expression through Cas9 or Base Editor to Treat β-Hemoglobinopathies. Cell Research 2020 30(3):276-278

5.      Li D*, Qiu Z, Shao Y, Chen Y, Guan Y, Liu M, Li Y, Gao N, Wang L, Lu X, Zhao Y*, Liu M*. Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nat Biotechnol. 2013 ;31(8):681-3

6.      Guan Y, Ma L, Li Q, Sun Z, Ma Li, Wu L, Wang L, Zeng L, Shao Y, Chen Y, Ma N, Lu W, Hu K, Han H, Yu Y, Huang Y, Liu M*, Li D*. CRISPR/Cas9 mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse. EMBO Mol Med. 2016 May 2;8(5):477-88.  (highlighted by EMBO Mol Med. Successful correction of hemophilia by CRISPR/Cas9 genome editing in vivo: delivery vector and immune responses are the key to success.)

7.      Chen Y, Ma J, Lu W, Tian M, Thauvin M, Yuan C, Volovitch M, Wang Q, Holst J, Liu M, Vriz S, Ye S*, Wang L*, Li D*. Heritable expansion of the genetic code in mouse and zebrafish. Cell Res. 2017 Feb;27(2):294-297. Editor’s Choice, Valda Vinson, Expanding the genetic code in vertebrates, Science 2017:Vol. 355, Issue 6320, pp. 36

8.      Qiu Z, Liu M, Chen Z, Shao Y, Pan H, Wei G, Yu C, Zhang L, Li X, Wang P, Fan HY, Du B, Liu B, Liu M*, Li D*. High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases. Nucleic Acids Res. 2013 Jun;41(11):e120

9.      Yang L, Zhang X, Wang L, Yin S, Zhu B, Xie L, Duan Q, Hu H, Zheng R, Wei Y, Peng L, Han H, Zhang J, Qiu W, Geng H, Siwko S, Zhang X, Liu M, Li D*. Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants. Protein Cell. 2018 Sep;9(9):814-819. (Cover story, Highlight by Protein & Cell. Volume 9, Issue 9, pp 752–753)

10.   Li H, Zhang Q, Gu Y, Wu Y, Wang Y, Wang L, Feng S, Hu Y, Zheng Y, Li Y, Ye H, Zhou B, Lin L, Liu M*, Yang H* and Li D*. Efficient photoactivatable Dre recombinase for cell type specific spatiotemporal control of genome engineering in the mouse. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33426-33435.

论文列表：

2021

1.      Wang W, Zhao X, Shao Y, Duan X, Wang Y, Li J, Li J, Li D, Li X, Wong J. Mutation-induced DNMT1 cleavage drives neurodegenerative disease. Sci Adv. 2021 Sep 3;7(36):eabe8511. doi: 10.1126/sciadv.abe8511. Yi Chuan. 2021 Jul 20;43(7):694-703. doi: 10.16288/j.yczz.20-423.

2.      Liang Y, Zhang X, Liu Y, Wang L, Ye Y, Tan X, Pu J, Zhang Q, Bao X, Wei X, Li D, Kurita R, Nakamura Y, Li D, Xu X. GATA zinc finger domain-containing protein 2A (GATAD2A) deficiency reactivates fetal haemoglobin in patients with β-thalassaemia through impaired formation of methyl-binding domain protein 2 (MBD2)-containing nucleosome remodelling and deacetylation (NuRD) complex. Br J Haematol. 2021 Jun;193(6):1220-1227. doi: 10.1111/bjh.17511.

3.      Zeng ZY, Lu JW, Cao XY, Wang XY, Li DL*.  A method for constructing GLP-1 overexpression intestinal organoids.

4.      Zhang L, Ge JY, Zheng YW*, Sun Z, Wang C, Peng Z, Wu B, Fang M, Furuya K, Ma X, Shao Y, Ohkohchi N, Oda T, Fan J, Pan G, Li D*, Hui L*. Survival-Assured Liver Injury Preconditioning (SALIC) Enables Robust Expansion of Human Hepatocytes in Fah-/- Rag2-/- IL2rg-/- Rats. Adv Sci (Weinh). 2021 Aug 11:e2101188. doi: 10.1002/advs.202101188.

5.      Wang L, Aschenbrenner D, Zeng Z, Cao X, Mayr D, Mehta M, […] Huang Y*, Li D*, Uhlig HH, Muise AM*. Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.Nat Genet. 2021 Mar 29. doi: 10.1038/s41588-021-00803-4. (Highlighted by News & Views: The sickening consequences of too much SYK signaling. Nat Genet. 2021 Mar 29.

6.      Li Y, Zheng R, Xu G, Huang Y, Li Y, Li D*, Geng H*. Generation and characterization of a novel rat model of primary hyperoxaluria type 1 with a nonsense mutation in alanine-glyoxylate aminotransferase. Am J Physiol Renal Physiol. 2021 Mar 1;320(3):F475-F484.

7.      Bao X, Zhang X, Wang L, Wang Z, Huang J, Zhang Q, Ye Y, Liu Y, Chen D, Zuo Y, Liu Q, Xu P, Huang B, Fang J, Lao J, Feng X, Li Y, Kurita R, Nakamura Y, Yu W, Ju C, Huang C, Mohandas N, Li D, Zhao C, Xu X. Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia. Am J Hum Genet. 2021 Apr 1;108(4):709-721.

2020

8.      Li H, Zhang Q, Gu Y, Wu Y, Wang Y, Wang L, Feng S, Hu Y, Zheng Y, Li Y, Ye H, Zhou B, Lin L, Liu M*, Yang H* and Li D*. Efficient photoactivatable Dre recombinase for cell type specific spatiotemporal control of genome engineering in the mouse. Proc. Natl. Acad. Sci. U.S.A.. 2020 Dec 29;117(52):33426-33435.

9.      Zheng R, Fang X, Chen X, Huang Y, Xu G, He L, Li Y, Niu X, Yang L, Wang L, Li D*, Geng H. Knockdown of lactate dehydrogenase by adeno-associated virus-delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1. Clin Transl Med. 2020 Dec;10(8):e261.

10.   Zhang X, Zhu B, Chen L, Xie L, Yu W, Wang Y, Li L, Yin S, Yang L, Hu H, Han H, Li Y, Wang L, Chen G, Ma X, Geng H, Huang W, Pang X, Yang Z, Wu Y, Siwko S, Kurita R, Nakamura Y, Yang L, Liu M, Li D.*. Dual Base Editor Catalyzes Both Cytosine and Adenine Base Conversions in Human Cells. Nat Biotechnol. 2020 Jun 1. doi: 10.1038/s41587-020-0527-y.

11.   Zhang X, Chen L, Zhu B, Wang L, Chen C, Hong M, Huang Y, Li H, Han H, Cai B, Yu W, Yin S, Yang L, Yang Z, Liu M, Zhang Y, Mao Z, Wu Y, Liu M, Li D*. Increasing efficiency and targeting scope of base editors through fusion of a single strand DNA binding protein domain. Nat Cell Biol. 2020 May 11. doi: 10.1038/s41556-020-0518-8.

12.   Yang L, Wang L, Huo Y, Chen X, Yin S, Hu Y, Zhang X, Zheng R, Geng H, Han H, Ma X, Liu M, Li H, Yu W, Liu M, Wang J, Li D*.Amelioration of an Inherited Metabolic Liver Disease Through Creation of a De Novo Start Codon by Cytidine Base Editing. Mol Ther. 2020 May 7;S1525-0016(20)30235-5

13.   Yin S, Ma L, Shao T, Zhang M, Guan Y, Wang L, Hu Y, Chen X, Han H, Shen N, Qiu W, Geng H, Yu Y, Li S, Yu W, Liu M, Li D*. Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor. Sci China Life Sci. 2020 Aug 17. doi: 10.1007/s11427-020-1744-6.

14.   Wei G, Gao N, Chen J, Fan L, Zeng Z, Gao G, Li L, Fang G, Hu K, Pang X, Fan HY, Clevers H, Liu M, Zhang X*, Li D*. ERK/MAPK signaling is essential for intestinal development through Wnt pathway modulation. Development. 2020 Aug 3:dev.185678.

15.   Li L, Mi D, Pei H, Duan Q, Wang X, Zhou W, Jin J, Li D, Liu M, Chen Y. In vivo target protein degradation induced by PROTACs based on E3 ligase DCAF15. Signal Transduct Target Ther. 2020 Jul 27;5(1):129.

16.   Wang L, Li L, Ma Y, Hu H, Li Q, Yang Y, Liu W, Yin S, Li W, Fu B, Kurita R, Nakamura Y, Liu M*, Lai Y*, Li D.*. Reactivation of γ-globin Expression through Cas9 or Base Editor to Treat β-Hemoglobinopathies. Cell Research 2020 30(3):276-278

17.   Zheng R, Li Y, Wang L, Fang X, Zhang J, He L, Yang L, Li D*, Geng H*. CRISPR/Cas9-mediated metabolic pathway reprogramming in a novel humanized rat model ameliorates primary hyperoxaluria type 1. Kidney Int. 2020 May 25:S0085-2538(20)30554-8.

18.   UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt/β-catenin signaling. Li L, Duan Q, Zeng Z, Zhao J, Lu J, Sun J, Zhang J, Siwko S, Wong J, Shi T, Zhang X, Liu M*, Chen J*, Li D.* Int J Cancer. 2020 May 6. doi: 10.1002/ijc.33036

19.   Li Q, Zhou L, Wang L, Li S, Xu G, Gu H, Li D, Liu M, Fang L, Wang Z, Han S, Zheng B. Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis. Eur J Immunol. 2020 Apr;50(4):525-536.

20.   Wan H, Wang Q, Chen X, Zeng Q, Shao Y, Fang H, Liao X, Li HS, Liu MG, Xu TL, Diao M, Li D, Meng B, Tang B, Zhang Z, Liao L. WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy. 2020 Mar;16(3):531-547.

21.   Li J, Wang R, Jin J, Han M, Chen Z, Gao Y, Hu X, Zhu H, Gao H, Lu K, Shao Y, Lyu C, Lai W, Li P, Hu G, Li J, Li D, Wang H, Wu Q, Wong J. USP7 negatively controls global DNA methylation by attenuating ubiquitinated histone-dependent DNMT1 recruitment. Cell Discov. 2020 Aug 24;6:58.

22.   Yu Y, Wu X, Guan N, Shao J, Li H, Chen Y, Ping Y, Li D, Ye H. Engineering a far-red light-activated split-Cas9 system for remote-controlled genome editing of internal organs and tumors. Sci Adv. 2020 Jul 10;6(28):eabb1777.

2019

23.   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.Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis.Nat Commun. 2019 Sep 13;10(1):4158.

24.   Wang T, Cao Y, Zheng Q, Tu J, Zhou W, He J, Zhong J, Chen Y, Wang J, Cai R, Zuo Y, Wei B, Fan Q, Yang J, Wu Y, Yi J, Li D, Liu M, Wang C, Zhou A, Li Y, Wu X, Yang W, Chin YE, Chen G, Cheng J. SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism. Mol Cell. 2019 Jun 25. pii: S1097-2765(19)30441-1.

25.   Luan P, Jian W, Xu X, Kou W, Yu Q, Hu H, Li D, Wang W, Feinberg MW, Zhuang J, Xu Y, Peng W. NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ. Nat Commun. 2019 Jun 28;10(1):2882.

26.   Wan H, Wang Q, Chen X, Zeng Q, Shao Y, Fang H, Liao X, Li HS, Liu MG, Xu TL, Diao M, Li D, Meng B, Tang B, Zhang Z, Liao L. WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy. 2019 Jun 23:1-17.

2018

27.   Zheng R, Fang X, He L, Shao Y, Guo N, Wang L, Liu M, Li D*, Geng H*. Generation of a primary hyperoxaluria type 1 disease model via CRISPR/Cas9 system in rats. Curr Mol Med. 2018 Dec 11.

28.   Zhang YL, Zhao LW, Zhang J, Le R, Ji SY, Chen C, Gao Y, Li D, Gao S, Fan HY. DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development.  EMBO J. 2018 Sep 14;37(18).

29.   Yang L, Zhang X, Wang L, Yin S, Zhu B, Xie L, Duan Q, Hu H, Zheng R, Wei Y, Peng L, Han H, Zhang J, Qiu W, Geng H, Siwko S, Zhang X, Liu M, Li D*. Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants. Protein Cell. 2018 Sep;9(9):814-819. (Cover story, Highlight by Protein & Cell Volume 9, Issue 9, pp 752–753)

30.   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*. Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats. J Biol Chem. 2018, 293(18):6883-6892

31.   Zhao Y, Yang Y, Xing R, Cui X, Xiao Y, Xie L, You P, Wang T, Zeng L, Peng W, Li D*, Chen H*, Liu M*. Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats. Atherosclerosis. 2018, 271:26-35.

32.   Zhang DL, Sun YJ, Ma ML, Wang YJ, Lin H, Li RR, Liang ZL, Gao Y, Yang Z, He DF, Lin A, Mo H, Lu YJ, Li MJ, Kong W, Chung KY, Yi F, Li JY, Qin YY, Li J, Thomsen ARB, Kahsai AW, Chen ZJ, Xu ZG, Liu M, Li D*, Yu X*, Sun JP*. Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility. Elife. 2018 Feb 2;7. pii: e33432

33.   Wen H, Ma H, Cai Q, Lin S, Lei X, He B, Wu S, Wang Z, Gao Y, Liu W, Liu W, Tao Q, Long Z, Yan M, Li D, Kelley KW, Yang Y, Huang H, Liu Q. Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma. Nat Med. 2018 Jan 1. doi: 10.1038/nm.4456.

2017

34.   Yue Z, Yuan Z, Zeng L, Wang Y, Lai L, Li J, Sun P, Xue X, Qi J, Yang Z, Zheng Y, Fang Y, Li D, Siwko S, Li Y, Luo J, Liu M. FASEB J. 2017 Dec 21.

35.   Wei Y, Zhang XH, Li DL*. The new favorite of gene editing technology-single base editors. Yi Chuan. 2017 Dec 20;39(12):1115-1121. （invited review）

36.   Peng W, Li M, Li H, Tang K, Zhuang J, Zhang J, Xiao J, Jiang H, Li D, Yu Y, Sham PC, Nattel S, Xu Y. Dysfunction of Myosin Light-Chain 4 (MYL4) Leads to Heritable Atrial Cardiomyopathy With Electrical, Contractile, and Structural Components: Evidence From Genetically-Engineered Rats. J Am Heart Assoc. 2017 Oct 28;6(11).

37.   Sun M, Ding J, Li D, Yang G, Cheng Z, Zhu Q. NUDT21 regulates 3'-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma. Cancer Lett. 2017 Dec 1;410:158-168.

38.   Liu XM, Zhang YL, Ji SY, Zhao LW, Shang WN, Li D, Chen Z, Tong C, Fan HY. Mitochondrial Function Regulated by Mitoguardin-1/2 Is Crucial for Ovarian Endocrine Functions and Ovulation. Endocrinology. 2017 Nov 1;158(11):3988-3999

39.   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. RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice. Cell Death Differ. 2017 Aug;24(8):1459-1469

40.   Zhang X, Wang L, Liu M, Li D*. CRISPR/Cas9 system: a powerful technology for in vivo and ex vivo gene therapy. Sci China Life Sci. 2017 May;60(5):468-475 （invited review）

41.   Zhang L, Li L, Gao G, Wei G, Zheng Y, Wang C, Gao N, Zhao Y, Deng J, Chen H, Sun J, Li D*, Zhang X*, Liu M*. Elevation of GPRC5A expression in colorectal cancer promotes tumor progression through VNN-1 induced oxidative stress. Int J Cancer. 2017 Jun 15;140(12):2734-2747 （Cover story）

42.   Chen Y, Ma J, Lu W, Tian M, Thauvin M, Yuan C, Volovitch M, Wang Q, Holst J, Liu M, Vriz S, Ye S*, Wang L*, Li D*. Heritable expansion of the genetic code in mouse and zebrafish. Cell Res. 2017 Feb;27(2):294-297.

43.   Lu J, Shao Y, Qin X, Liu D, Chen A, Li D*, Liu M*, Wang X*.CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug metabolism and pharmacokinetics research.Sci Rep. 2017 Feb 20;7:42922..

44.   Chen R, Zhang Q, Duan X, York P, Chen GD, Yin P, Zhu H, Xu M, Chen P, Wu Q, Li D, Samarut J, Xu G, Zhang P, Cao X, Li J, Wong J. The 5-hydroxymethylcytosine (5hmC) reader Uhrf2 is required for normal levels of 5hmC in mouse adult brain and spatial learning and memory.J Biol Chem. 2017 Jan 23. pii: jbc.M116.754580

2016

45.   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.

46.   You P, Hu H, Chen Y, Zhao Y, Yang Y, Wang T, Xing R, Shao Y, Zhang W, Li D*, Chen H*, Liu M*. Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats. Sci Rep. 2016 Oct 7;6:34938.

47.   Chen Y, Liu X, Zhang Y, Wang H, Ying H, Liu M, Li D, Lui KO, Ding Q. A Self-restricted CRISPR System to Reduce Off-target Effects. Mol Ther. 2016 Sep;24(9):1508-10.

48.   Zhang L, Shao Y, Li L, Tian F, Cen J, Chen X, Hu D, Zhou Y, Xie W, Zheng Y, Ji Y, Liu M, Li D*, Hui L*. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I. Sci Rep. 2016 Aug 11;6:31460

49.   Chen Y, Lu W, Gao N, Long Y, Shao Y, Liu MZ, Chen H, Ye S, Ma X, Liu M*, Li D*. Generation of obese rat model by transcription activator-like effector nucleases targeting the leptin receptor gene. Sci China Life Sci. 2016 60(2):152-157.

50.   Luo J, Yang Z, Ma Y, Yue Z, Lin H, Qu G, Huang J, Dai W, Li C, Zheng C, Xu L, Chen H, Wang J, Li D, Siwko S, Penninger JM, Ning G, Xiao J, Liu M. LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption. Nat Med. 2016 May;22(5):539-46

51.   Zhang Y, Zeng Z, Zhao J, Li D, Liu M, Wang X.Measurement of Rhodamine 123 in Three-Dimensional Organoids: A Novel Model for P-Glycoprotein Inhibitor Screening.Basic Clin Pharmacol Toxicol. 2016 Apr 6.

52.   Guan Y, Ma L, Li Q, Sun Z, Ma Li, Wu L, Wang L, Zeng L, Shao Y, Chen Y, Ma N, Lu W, Hu K, Han H, Yu Y, Huang Y, Liu M*, Li D*. CRISPR/Cas9 mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse. EMBO MOL MED. 2016 May 2;8(5):477-88.  

53.   Wang X*, Tang Y, Lu J, Shao Y, Qin X, Li Y, Wang L, Li D*,Liu M*. Characterization of novel cytochrome P450 2E1 knockout rat model generated by CRISPR/Cas9. Biochem Pharmacol. 2016 Apr 1;105:80-90. 

54.   Liu XM, Zhang YP, Ji SY, Li BT, Tian X, Li D, Tong C, Fan HY. Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions. Oncotarget. 2016 Jan 12;7(2):1155-67.

2015

55.   Wang L, Shao Y, Guan Y, Li L, Wu L, Chen F, Liu M, Chen H, Ma Y, Ma X, Liu M*, Li D*. Large genomic fragment deletion and functional gene cassette knock-in via Cas9 protein mediated genome editing in one-cell rodent embryos.Sci Rep. 2015 Dec 1;5:17517  

56.   Bai M, Li Q, Shao Y, Huang Y, Li D*, Ma Y*. Generation of site-specific mutant mice using the CRISPR/Cas9 system.Yi Chuan. 2015 Oct;37(10):1029-35.

57.   Guan Y, Zhang L, Li X, Zhang X, Liu S, Gao N, Li L, Gao G, Wei G, Chen Z, Zheng Y, Ma X, Siwko S, Chen JL, Liu M*, Li D*.Repression of Mammalian Target of Rapamycin Complex 1 Inhibits Intestinal Regeneration in Acute Inflammatory Bowel Disease Models. J Immunol. 2015 May 29. pii: 1303356 

58.   Liu XM, Zhang YP, Ji SY, Li BT, Tian X,Li D, Tong C, Fan HY. Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions.Oncotarget. 2015 doi: 10.18632/oncotarget.6713  

59.   Deng L, Jiang C, Chen L, Jin J, Wei J, Zhao L, Chen M, Pan W, Xu Y, Chu H, Wang X, Ge X, Li D, Liao L, Liu M, Li L, Wang P. The Ubiquitination of RagA GTPase by RNF152 Negatively Regulates mTORC1 Activation. Mol Cell. 2015 Jun 4;58(5):804-18  

60.   Fan G, Sun L, Shan P, Zhang X, Huan J, Zhang X, Li D, Wang T, Wei T, Zhang X, Gu X, Yao L, Xuan Y, Hou Z, Cui Y, Cao L, Li X, Zhang S, and Wang C. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nat Commun 2015 Oct 6;6:8450

61.   Fang P, Xu W, Li D, Zhao X, Dai J, Wang Z, Yan X, Qin M, Zhang Y, Xu C, Wang L, Qiao Z. A novel acrosomal protein, IQCF1, involved in sperm capacitation and the acrosome reaction. Andrology. 2015 Mar;3(2):332-44. 

2014

62.   Guan Y, Shao Y, Li D*，Liu M*. Generation of Site-Specific Mutations in the Rat Genome Via CRISPR/Cas9. Methods Enzymol. 2014 ;546:297-317  

63.   Shao Y, Guan Y, Wang L, Qiu Z, Liu M, Chen Y, Wu L, Li Y, Ma X, Liu M*, Li D*. Genome editing in the rat using CRISPR-Cas and injection of RNAs into one-cell embryos. Nature Protocols. 2014 (10):2493-512  

64.   Cui H, Wang Y, Huang H, Yu W, Bai M, Zhang L, Bryan BA, Wang Y, Luo J, Li D*, Ma Y*, Liu M*.GPR126 Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Signaling. J Biol Chem.2014 Sep 12. pii: jbc.M114.571000  

65.   Guan X, Duan Y, Zeng Q, Pan H, Qian Y, Li D*, Cao X*, Liu M*. Lgr4 Deficiency Induces Ataxia-like Phenotype in Mice and Impairs Long-term Depression at Cerebellar Parallel fiber-Purkinje Cell Synapses.J Biol Chem. 2014 Sep 19;289(38):26492-504.  

66.   Pan H, Cui H, Liu S, Qian Y, Wu H, Li L, Guan Y, Guan X, Zhang L, Fan HY, Ma Y, Li R, Liu M*,Li D*. Lgr4 gene regulates Corpus Luteum Maturation through Modulation of the WNT mediated EGFR-ERK Signaling Pathway. Endocrinology. 2014 May 30:en20132183.  

67.   Yi T, Weng J, Siwko S, Luo J, Li D, Liu M.LGR4/GPR48 inactivation leads to aniridia-genitourinary anomalies-mental retardation syndrome defects. J Biol Chem. 2014 Mar 28;289(13):8767-80

2013

68.   Li D*, Qiu Z, Shao Y, Chen Y, Guan Y, Liu M, Li Y, Gao N, Wang L, Lu X, Zhao Y*, Liu M*. Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nature Biotechnol. 2013 ;31(8):681-3. 

69.   Qiu Z, Liu M, Chen Z, Shao Y, Pan H, Wei G, Yu C, Zhang L, Li X, Wang P, Fan HY, Du B, Liu B, Liu M, Li D*. High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases. Nucleic Acids Res. 2013 Jun;41(11):e120.

70.   Liu S, Qian Y, Li L, Wei G, Guan Y, Pan H, Guan X, Zhang L, Lu X, Zhao Y, Liu M*, Li D*.Lgr4 deficiency increases susceptibility and severity of dextran sodium sulphate induced inflammatory bowel disease in mice. J Biol Chem. 2013 288: 8794-8803. [paper of the week]  

71.   Qian Y, Liu S, Guan Y, Pan H, Guan X, Qiu Z, Li L, Gao N, Zhao Y, Li X, Lu Y, Liu M*, Li D.* Lgr4 mediated Wnt/β-catenin signaling in peritubular myoid cells is essential for spermatogenesis.  Development. 2013;140(8):1751-61. 

72.   Luo W, Rodriguez M, Valdez JM, Zhu X, Tan K, Li D, Siwko S, Xin L, Liu M. Lgr4 is a Key Regulator of Prostate Development and Prostate Stem Cell Differentiation. Stem Cells. 2013;31(11):2492-505.  

73.   Wang Y, Dong J, Li D, Lai L, Siwko S, Li Y, Liu M. Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2. Stem Cells. 2013;31(9):1921-31.  

74.   Du B, Luo W, Li R, Tan B, Han H, Lu X, Li D, Qian M, Zhang D, Zhao Y, Liu M. Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression. J Biol Chem. 2013; 288(21):15131-41. 

2013年以前

75.   Yu W, Qiu Z, Gao N, Wang L, Cui H, Qian Y, Jiang L, Luo J, Yi Z, Lu H, Li D*, and Liu M* PAK1IP1, a ribosomal stress-induced nucleolar protein, regulates cell proliferation via the p53-MDM2 loop, Nucleic Acids Res 2010 39(6):2234-48.  

76.   Yang Z, Li C, Wang X, Zhai C, Yi Z, Wang L, Liu B, Du B, Wu H, Guo X, Liu M, Li D*, Luo J*. Dauricine induces apoptosis, inhibits proliferation and invasion through inhibiting NF-kappaB signaling pathway in colon cancer cells. J Cell Physiol. 2010 Oct;225(1):266-75.  

77.   Li, D., Yu, W. and Liu, M. (2009) Regulation of KiSS1 gene expression. Peptides, 30, 130-138. 

78.   Li, D*., Niu, Z., Yu, W., Qian, Y., Wang, Q., Li, Q., Yi, Z., Luo, J., Wu, X., Wang, Y. Schwartz RJ, Liu M. (2009) SMYD1, the myogenic activator, is a direct target of serum response factor and myogenin. Nucleic Acids Res, 37, 7059-7071.

79.   Li, D., Mitchell, D., Luo, J., Yi, Z., Cho, S.G., Guo, J., Li, X., Ning, G., Wu, X. and Liu, M. (2007) Estrogen regulates KiSS1 gene expression through estrogen receptor alpha and SP protein complexes. Endocrinology, 148, 4821-4828. 

80.   Cho SG, Li D, Tan K, Siwko SK, Liu M. KiSS1 and its G-protein-coupled receptor GPR54 in cancer development and metastasis. Cancer Metastasis Rev. 2012；31(3-4):585-91.  

81.   Dai F, Chen Y, Song Y, Huang L, Zhai D, Dong Y, Lai L, Zhang T, Li D, Pang X, Liu M, Yi Z. A natural small molecule harmine inhibits angiogenesis and suppresses tumour growth through activation of p53 in endothelial cells. PLoS One. 2012;7(12):e52162  

82.   Cho SG, Wang Y, Rodriguez M, Tan K, Zhang W, Luo J, Li D, Liu M Haploinsufficiency in the prometastasis Kiss1 receptor Gpr54 delays breast tumor initiation, progression, and lung metastasis. Cancer Res. 2011 15;71(20):6535-46. 

83.   Dong Y, Lu B, Zhang X, Zhang J, Lai L, Li D, Wu Y, Song Y, Luo J, Pang X, Yi Z, Liu M. Cucurbitacin E, a Tetracyclic Triterpenes Compound from Chinese Medicine, Inhibits Tumor Angiogenesis through VEGFR2 Mediated Jak2/STAT3 Signaling Pathway.Carcinogenesis.2010 Aug 23 

84.   Yi, T., Tan, K., Cho, S.G., Wang, Y., Luo, J., Zhang, W.,Li, D. and Liu, M. Regulation of embryonic kidney branching morphogenesis and glomerular development by KISS1 receptor (GPR54) through NFAT2 and SP1 mediated bmp7 expression. J Biol Chem. 285(23):17811-20

85.   Li, X.Y., Lu, Y., Sun, H.Y., Wang, J.Q., Yang, J., Zhang, H.J., Fan, N.G., Xu, J., Jiang, J.J., Liu, R.Y., Li,D. et al. (2010) G protein-coupled receptor 48 upregulates estrogen receptor alpha expression via cAMP/PKA signaling in the male reproductive tract. Development, 137, 151-157.

86.   Li, C., Yang, Z., Zhai, C., Qiu, W., Li, D., Yi, Z., Wang, L., Tang, J., Qian, M., Luo, J. et al. Maslinic acid potentiates the anti-tumor activity of tumor necrosis factor alpha by inhibiting NF-kappaB signaling pathway. Mol Cancer, 9, 73

87.   Yi, Z.F., Cho, S.G., Zhao, H., Wu, Y.Y., Luo, J., Li, D., Yi, T., Xu, X., Wu, Z. and Liu, M. (2009) A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c-Src phosphorylation in VEGF-induced human umbilical endothelial cells. Int J Cancer, 124, 843-852.

88.   Wang, L., Kuang, L., Pan, X., Liu, J., Wang, Q., Du, B., Li, D., Luo, J., Liu, M., Hou, A. et al. (2010) Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP-1. Int J Cancer. 127(5):1220-9

89.   Luo, J., Zhou, W., Zhou, X., Li, D., Weng, J., Yi, Z., Cho, S.G., Li, C., Yi, T., Wu, X. et al. (2009) Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development, 136, 2747-2756.

90.   Cho, S.G., Yi, Z., Pang, X., Yi, T., Wang, Y., Luo, J., Wu, Z., Li, D. and Liu, M. (2009) Kisspeptin-10, a KISS1-derived decapeptide, inhibits tumor angiogenesis by suppressing Sp1-mediated VEGF expression and FAK/Rho GTPase activation. Cancer Res, 69, 7062-7070.

91.   Cho, S.G., Li, D., Stafford, L.J., Luo, J., Rodriguez-Villanueva, M., Wang, Y. and Liu, M. (2009) KiSS1 suppresses TNFalpha-induced breast cancer cell invasion via an inhibition of RhoA-mediated NF-kappaB activation. J Cell Biochem, 107, 1139-1149.

92.   Yu, W., Li, Y., Zhou, X., Deng, Y., Wang, Z., Yuan, W., Li, D., Zhu, C., Zhao, X., Mo, X. et al. (2008) A novel human BTB-kelch protein KLHL31, strongly expressed in muscle and heart, inhibits transcriptional activities of TRE and SRE.Mol Cells, 26, 443-453.

93.   Weng, J., Luo, J., Cheng, X., Jin, C., Zhou, X., Qu, J., Tu, L., Ai, D., Li, D., Wang, J. et al.(2008) Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2. Proc Natl Acad Sci U S A, 105, 6081-6086.

94.   Song, H., Luo, J., Luo, W., Weng, J., Wang, Z., Li, B., Li, D. and Liu, M. (2008) Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway. J Biol Chem, 283, 36687-36697.

95.   Ma, W., Stafford, L.J., Li, D., Luo, J., Li, X., Ning, G. and Liu, M. (2007) GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. J Cell Biochem, 100, 1376-1386.

96.   Mitchell DC, Stafford LJ, Li D, Bar-Eli M, Liu M. (2007) Transcriptional regulation of KiSS-1 gene expression in metastatic melanoma by specificity protein-1 and its coactivator DRIP-130. Oncogene. 26(12):1739-47

97.   Zhu Y, Wang Y, Xia C, Li D, Li Y, Zeng W, Yuan W, Liu H, Zhu C, Wu X, Liu M. WDR26: a novel Gbeta-like protein, suppresses MAPK signaling pathway.J Cell Biochem. 2004 93(3):579-87

98.   Huang C, Wang Y, Li D, Li Y, Luo J, Yuan W, Ou Y, Zhu C, Zhang Y, Wang Z, Liu M, Wu X. Inhibition of transcriptional activities of AP-1 and c-Jun by a new zinc finger protein ZNF394. Biochem Biophys Res Commun. 2004 320(4):1298-305.

99.   Yi Z, Li Y, Ma W, Li D, Zhu C, Luo J, Wang Y, Huang X, Yuan W, Liu M, Wu X. A novel KRAB zinc-finger protein, ZNF480, expresses in human heart and activates transcriptional activities of AP-1 and SRE.Biochem Biophys Res Commun. 320(2):409-15.

100.Liu H, Zhu C, Luo J, Wang Y, Li D, Li Y, Zhou J, Yuan W, Ou Y, Liu M, Wu X. ZNF411, a novel KRAB-containing zinc-finger protein, suppresses MAP kinase signaling pathway.Biochem Biophys Res Commun. 2004;320(1):45-53.

101.Zeng W, Yuan W, Wang Y, Jiao W, Zhu Y, Huang C, Li D, Li Y, Zhu C, Wu X, Liu M. Expression of a novel member of sorting nexin gene family, SNX-L, in human liver development.Biochem Biophys Res Commun. 2002 299(4):542-8.

个人荣誉：

教育部“长江学者奖励计划”青年学者

2018年度教育部自然科学一等奖（排名第二）

2018年度海南省科技进步二等奖（排名第四）