葛微教授

实验室成员

实验室聚餐

1. 国家自然科学基金面上项目，DNA甲基化调控的转录因子HSF4在DC细胞天然免疫应答中的调控机制研究，2014/1-2017/12，主持

2. 国家自然科学基金面上项目，FLT1介导神经元APP内吞和Aβ生成在阿尔兹海默病中的作用及分子机制研究，2020/1-2023/12，主持

3. 诺和诺德－协和糖尿病研究英才基金，To Test whether FTO inhibition will regulateghrelin expression and is useful for diabetes，2014/4-2017/3，主持

4. 国家自然科学基金重大培育项目，基于中国人脑组织库的阿尔茨海默病分子机制研究，2017/01-2019/12，主要参与

5. 国家自然科学基金面上项目，CHIP在甲状腺癌发生发展过程中的作用和调控机制研究，2016/1-2019/12，主要参与

6. 医学与健康科技创新工程，炎症与重大疾病的基础与干预研究，2016/1-2020/12，参与

1. 基于中国人脑组织库，系统性比较了阿尔茨海默病（AD）人脑，年龄匹配的正常衰老人脑和APP/PS1转基因AD模型鼠脑中淀粉状斑块（AmyloidPlaques, APs）的蛋白组学特征。鉴定出40余种高度富集于人脑APs的蛋白组分，并且详细阐述了人脑与模型小鼠脑的异同。发现AD模型鼠脑中多种明显激活的信号通路在人脑中并未发生明显变化，提示其种属间病理机制可能存在不同。该研究为AD病理机制提供了独特见解，也为未来AD诊断及治疗靶点的研发奠定了坚实基础。（参考文献：Xiong, F., W. Ge, and C.Ma, Alzheimers Dement,2019. 15(3): p. 429-440.）

2. 衰老是全人类面临的重要问题，我国人口老龄化问题尤为严峻。脑衰老在衰老中占有重要地位，海马和颞叶随着衰老极易损伤。因此，揭示海马和颞叶在衰老过程中动态蛋白表达谱具有重要的研究意义和社会价值。课题组利用蛋白质组学技术系统性比较了不同年龄段海马和颞叶区蛋白谱变化，发现海马区衰老过程中，电子传递链和突触泡蛋白表达下调，并且正常衰老过程中的动态改变蛋白与AD中的存在差异；而在颞叶衰老过程中，细胞的结构稳定性下降，纤维化和自噬增加。（参考文献：Xu, B., et al., ExpGerontol, 2016. 73: p. 31-41；Xu, B., et al.,Neurobiol Aging, 2016. 39: p.46-56.）

3. 近年来我国结直肠癌的发病率和死亡率逐年攀升，本课题组试图解析结直肠癌发病机制，寻找适合的诊断、预后指标和治疗靶点，为防治结直肠癌提供基础数据。课题组发现了外泌体肿瘤活性蛋白FN1介导结直肠癌转移的新机制；鉴定了外泌体中潜在的预后标志物LRG1和SPARC；并利用CRISPR/Cas9敲除技术发现了MeCP2的促癌作用，其机制为通过上调表观调节转录调节因子ZEB1，促进了结直肠癌细胞的侵袭和迁移。（参考文献：Luo, D. and W. Ge, Cancers (Basel),2020. 12(3)；Zhong, M.E., et al.,EBioMedicine, 2019；31; Chen,Y., et al., IntJ Cancer, 2017. 140(4): p. 900-913.）

4. 基于小分子筛选平台，课题组筛选出了有潜力治疗FLT3突变型急性髓性白血病（Acute Myeloid Leukemia，AML）的新型小分子化合物MZH29，该化合物对FLT3-ITD突变型急性髓性白血病具有治疗作用，并对FLT3-D835H/Y/V，FLT3-K663Q和FLT3-ITD-F691L等突变类型仍然有效。该研究证实了MZH29作为候选药物的开发潜力，也为FLT3-ITD突变型AML患者的治疗带来新的希望。（参考文献：Xu, B., et al., Leukemia, 2017. 31(4): p. 913-921）

发表文章

以第一作者或通讯作者共发表文章66篇，其中IF>10的7篇，IF>5的24篇。

2022年（1篇）

1. Gao Y, Liu J, Wang J, LiuY, Zeng LH, Ge W, Ma C. Proteomic analysis of human hippocampal subfieldsprovides new insights into the pathogenesis of Alzheimer's disease and the roleof glial cells. Brain Pathol. 2022 Jan 11:e13047. doi: 10.1111/bpa.13047.

2021年（7篇）

2.    Gao, Y., Chen, Y., Wang, L., Li, C., &Ge, W. (2021). Serum-derived extracellular vesicles inhibit osteoclastogenesisin active-phase patients with SAPHO syndrome. Ther Adv Musculoskelet Dis, 13,1759720x211006966. doi:10.1177/1759720x211006966

3.    Jia, Y., Wang, X., Chen, Y., Qiu, W., Ge,W., & Ma, C. (2021). Proteomic and Transcriptomic Analyses RevealPathological Changes in the Entorhinal Cortex Region that Correlate Well withDysregulation of Ion Transport in Patients with Alzheimer's Disease. MolNeurobiol. doi:10.1007/s12035-021-02356-3

4.    Wang, T., Zhang, Y., Chen, W., Tao, J., Xue,Q., Ge, W., . . . Ma, C. (2021). Proteomic changes in the hippocampus and motorcortex in a rat model of cerebral palsy: Effects of topical treatment.Biomedicine & Pharmacotherapy, 133, 110844. doi:https://doi.org/10.1016/j.biopha.2020.110844

5.    Wang, X., Han, C., Jia, Y., Wang, J., Ge,W., & Duan, L. (2021). Proteomic Profiling of Exosomes From HemorrhagicMoyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells. Stroke,Strokeaha120032297. doi:10.1161/strokeaha.120.032297

6.    Zhang P, Zhang Y, Pan M, Liu Z, Li J, PengL, Zhou J, Hu C, Liu S, Zeng X, Ge W, Zhang W. Proteomic analyses ofplasma-derived exosomes in immunoglobulin (Ig) G4-related disease and theirpotential roles in B cell differentiation and tissue damage. J Autoimmun. 2021Aug;122:102650. doi: 10.1016/j.jaut.2021.102650. Epub 2021 Jun 6. PMID:34107438.

7.    Zhang, Y., Li, C. Y., Ge, W., & Xiao, Y.(2021). Exploration of the Key Proteins in the Normal-Adenoma-CarcinomaSequence of Colorectal Cancer Evolution Using In-Depth Quantitative Proteomics.J Oncol, 2021, 5570058. doi:10.1155/2021/5570058

8.    Zhang Y, Pan M, Li CY, Li JY, Ge W, Xu L,Xiao Y. Exploration of the typical features of tubulovillous adenoma usingin-depth quantitative proteomics analysis. Bioengineered. 2021Dec;12(1):6831-6843. doi: 10.1080/21655979.2021.1971036. 

2020年（5篇）

9.   Zhang, Y., et al., Proteomic profiling ofsclerotic hippocampus revealeddysregulated packaging of vesicularneurotransmitters in temporal lobe epilepsy.Epilepsy Res, 2020. 166: p.106412.

10.   Wang, X., et al., Comparison of proteomealterations during aging in thetemporal lobe of humans and rhesus macaques.Exp Brain Res, 2020. 238(9): p.1963-1976.

11.   Meng, S., et al., Proteomics profiling andpathway analysis of hippocampal agingin rhesus monkeys. BMC Neurosci, 2020.21(1): p. 2.

12.   Luo, D. and W. Ge, MeCP2 PromotesColorectal Cancer Metastasis by ModulatingZEB1 Transcription. Cancers (Basel),2020. 12(3).

13.   Liu, Y., et al., Proteome Profiling of LungTissues in Chronic ObstructivePulmonary Disease (COPD): Platelet andMacrophage Dysfunction Contribute to thePathogenesis of COPD. Internationaljournal of chronic obstructive pulmonarydisease, 2020. 15: p. 973-980.

2019年（12篇）

14.   Zhong,M.E., et al., LncRNA H19 regulatesPI3K-Akt signal pathway by functioningas aceRNA and predicts poor prognosis incolorectal cancer: integrative analysisofdysregulated ncRNA-associated ceRNAnetwork. Cancer Cell Int, 2019. 19: p.148.

15.   Zhong,M.E., et al., Serum extracellularvesicles contain SPARC and LRG1 asbiomarkersof colon cancer and differ bytumour primary location. EBioMedicine,2019.

16.   Zhan,S., et al., In-Depth ProteomicsAnalysis to Identify Biomarkers ofPapillaryThyroid Cancer Patients Older Than45 Years with Different Degrees ofLymphNode Metastases. PROTEOMICS – ClinicalApplications, 2019. 13(5): p.1900030.

17.   Zhan,S., et al., Clinicopathologicalpredictors of occult lateral neck lymphnodemetastasis in papillary thyroidcancer: A meta-analysis. Head Neck,2019.41(7): p. 2441-2449.

18.   Zhan, S.,J. Li, and W. Ge, MultifacetedRoles of Asporin in Cancer:CurrentUnderstanding. Front Oncol, 2019. 9: p. 948.

19.   Xiong,F., W. Ge, and C. Ma, Quantitativeproteomics reveals distinct compositionofamyloid plaques in Alzheimer'sdisease. Alzheimers Dement, 2019. 15(3):p.429-440.

20.   Xie, Y.,et al., Bench-to-bedsidestrategies for osteoporotic fracture: Fromosteoimmunologyto mechanosensation.Bone Research, 2019. 7(1): p. 25.

21.   Xie, Y.,et al., The potential risks of C-Cchemokine receptor 5-edited babies inbonedevelopment. Bone Research, 2019.7(1): p. 4.

22.   Xie, Y.,et al., Dose-dependent roles ofaspirin and othernon-steroidalanti-inflammatory drugs in abnormal boneremodeling and skeletalregeneration.Cell Biosci, 2019. 9: p. 103.

23.   Wang, X.,et al., Rapamycin regulatescholesterol biosynthesis and cytoplasmicribosomalproteins in hippocampus andtemporal lobe of APP/PS1 mouse. Journal oftheNeurological Sciences, 2019. 399:p. 125-139.

24.   Wang, X.,et al., Proteome Profiling ofCerebral Vessels in RhesusMacaques:Dysregulation of Antioxidant Activity andExtracellular MatrixProteinsContributes to Cerebrovascular Aging in RhesusMacaques. Front AgingNeurosci,2019. 11: p. 293.

25.   Meng, S.,et al., The interactome andproteomic responses of ALKBH7 in cell linesbyin-depth proteomics analysis.Proteome science, 2019. 17: p. 8-8.

2018年（7篇）

26.   Zhan, S.,et al., Multiple roles of Ring 1and YY1 binding protein in physiologyanddisease. J Cell Mol Med, 2018. 22(4):p. 2046-2054.

27.   Zhan, S.,et al., Quantitative ProteomicsAnalysis of Sporadic Medullary ThyroidCancerReveals FN1 as a Potential NovelCandidate Prognostic Biomarker.Oncologist,2018.

28.   Xu, B.,et al., Proteomic Profiling ofBrain and Testis Reveals the DiverseChanges inRibosomal Proteins in fmr1Knockout Mice. Neuroscience, 2018. 371: p.469-483.

29.   Xie, Y.,et al., Involvement ofserum-derived exosomes of elderly patients withboneloss in failure of boneremodeling via alteration of exosomalbone-relatedproteins. Aging Cell, 2018.17(3): p. e12758.

30.   Luo, D.,et al., Proteomics study of serumexosomes from papillary thyroidcancerpatients. Endocr Relat Cancer, 2018.25(10): p. 879-891.

31.   Guo, Y.,et al., Quantitative proteinprofiling and pathway analysis ofspinalarteriovenous malformations. MicrovascRes, 2018. 120: p. 47-54.

32.   Gao, Y.and W. Ge, The histonemethyltransferase DOT1L inhibitsosteoclastogenesis andprotects againstosteoporosis. Cell Death Dis, 2018. 9(2):p. 33.

2017年（9篇）

33.   Zuo, F.,et al., IntrastriatalTransplantation of Human Neural Stem CellsRestores theImpaired SubventricularZone in Parkinsonian Mice. Stem Cells, 2017.

34.   Zhan, S.,T. Wang, and W. Ge, Multiplefunctions of the E3 ubiquitin ligase CHIPinimmunity. Int Rev Immunol, 2017: p.1-13.

35.   Xu, B., et al., MZH29 is a novelpotentinhibitor that overcomes drug resistanceFLT3 mutations in acutemyeloidleukemia. Leukemia, 2017. 31(4): p. 913-921.

36.   Xu, B.,et al., Quantitative proteomicprofiling for clarification of the crucialrolesof lysosomes in microbialinfections. Mol Immunol, 2017. 87: p. 122-131.

37.   Xie, Y.,et al., The roles of bone-derivedexosomes and exosomal microRNAs inregulatingbone remodelling. J Cell Mol Med,2017. 21(5): p. 1033-1041.

38.   Wang, X.,et al., Dysregulation ofcell-cell interactions in brainarteriovenousmalformations: A quantitativeproteomic study. Proteomics Clin Appl,2017.

39.   He, Q.and W. Ge, The tandem Agenet domainof fragile X mental retardationproteininteracts with FUS. Sci Rep, 2017. 7(1):p. 962.

40.   Gao, Y.,et al., Comprehensive proteomeanalysis of lysosomes reveals thediversefunction of macrophages in immuneresponses. Oncotarget, 2017. 8(5):p.7420-7440.

41.   Chen, Y.,et al., Protein content andfunctional characteristics ofserum-purifiedexosomes from patients withcolorectal cancer revealed byquantitativeproteomics. Int J Cancer, 2017.140(4): p. 900-913.

2016年（10篇）

42.   Xu, L.,et al., Quantitative proteomicsreveals that distantrecurrence-associatedprotein R-Ras and Transgelin predictpost-surgical survivalin patients withStage III colorectal cancer. Oncotarget,2016.

43    Xu,B.,et al., Temporal lobe in humanaging: A quantitative protein profiling studyofsamples from Chinese HumanBrain Bank. Exp Gerontol, 2016. 73: p. 31-41.

44.   Xu, B.,et al., Protein profile changes inthe frontotemporal lobes in humanseveretraumatic brain injury. Brain Res,2016.

45.   Xu, B.,et al., Quantitative proteinprofiling of hippocampus during humanaging.Neurobiol Aging, 2016. 39: p.46-56.

46.   Xiong,Q., et al., Investigation ofproteome changes in osteoclastogenesis inlowserum culture system usingquantitative proteomics. Proteome Sci, 2016. 14:p.8.

47.   Xiong,Q., et al., The roles of interferonsin osteoclasts andosteoclastogenesis.Joint Bone Spine, 2016.

48.   Xiong,Q., et al., Protein profiling ofpapillary thyroid carcinoma with andwithoutlymph node metastasis: a proteomicstudy. Int J Clin Exp Pathol, 2016.9(3): p.3057-3069.

49.   Xiong, Q.and W. Ge, Gene mutations inCushing's disease. Biomed Rep, 2016. 5(3):p.277-282.

50.   Xin, L.,et al., Proteomics study revealsthat the dysregulation of focaladhesion andribosome contribute to earlypregnancy loss. Proteomics Clin Appl,2016. 10(5):p. 554-63.

51.   Xie, Y.,et al., The roles of bone-derivedexosomes and exosomal microRNAs inregulatingbone remodelling. J Cell Mol Med,2016.

2015年（4篇）

52.   Xiong,Q., et al., Proteomic study ofdifferent culture medium serum volumefractionson RANKL-dependent RAW264.7cells differentiating into osteoclasts.ProteomeSci, 2015. 13: p. 16.

53.   Xiong,Q., et al., Proteomic Analysis ofEstrogen-Mediated Signal TransductioninOsteoclasts Formation. Biomed Res Int,2015. 2015: p. 596789.

54.   Xie, Y.,et al., The Multiple Roles ofMicrorna-223 in Regulating BoneMetabolism.Molecules, 2015. 20(10): p.19433-48.

55.   Ge, W.,et al., The Roles of Lysosomes inInflammation and Autoimmune Diseases.Int RevImmunol, 2015. 34(5): p. 415-31.

2014年（3篇）

56.   Tang, P.,et al., The role of microRNAs inosteoclasts and osteoporosis. RNABiol, 2014.11(11): p. 1355-63.

57.   He, Q.,et al., Purified anti-CD3 xanti-HER2 bispecific antibodypotentiatescytokine-induced killer cells of poorspontaneous cytotoxicityagainst breastcancer cells. Cell Biosci, 2014. 4(1):p. 70.

58.   He, Q.and W. Ge, FMRP: a new chapter withchromatin. Protein Cell, 2014. 5(12):p.885-8.

2008-2013年（8篇）

59.   Yang, M.,et al., Substrate selectivityanalyses of factor inhibitinghypoxia-induciblefactor. Angew Chem Int Ed Engl,2013. 52(6): p. 1700-4.

60.   Ge, W.,et al., Oxygenase-catalyzedribosome hydroxylation occurs in prokaryotesandhumans. Nat Chem Biol, 2012.8(12): p. 960-2.

61.   Yang, M.,et al., Asparagine and aspartatehydroxylation of the cytoskeletalankyrinfamily is catalyzed byfactor-inhibiting hypoxia-inducible factor. J BiolChem,2011. 286(9): p.7648-60.

62.   Loenarz,C., et al., PHF8, a geneassociated with cleft lip/palate and mentalretardation,encodes for anNepsilon-dimethyl lysine demethylase. Hum Mol Genet,2010.19(2): p. 217-22.

63.   Ge, W.,et al., The crystal structure of anLLL-configured depsipeptidesubstrateanalogue bound to isopenicillin Nsynthase. Org Biomol Chem, 2010.8(1): p.122-7.

64.   Ge, W.,et al., Crystallographic studies onthe binding of selectively deuteratedLLD-and LLL-substrate epimers byisopenicillin N synthase. Biochem BiophysResCommun, 2010. 398(4): p. 659-64.

65.   Ge, W.,et al., Structural studies on thereaction of isopenicillin N synthasewith asterically demanding depsipeptidesubstrate analogue. Chembiochem,2009.10(12): p. 2025-31.

66.   Ge, W.,et al., Isopenicillin N synthasemediates thiolate oxidation to sulfenatein adepsipeptide substrate analogue:implications for oxygen binding and a linktonitrile hydratase? J Am Chem Soc,2008. 130(31): p. 10096-102.