南京大学模式动物研究所

主要研究方向为细胞生物学、发育生物学、小鼠遗传学; 主要学术成果：①结合化学诱变和表型筛选，建立20余种遗传性疾病的小鼠模型并克隆突变基因；②证明蛋白磷酸酶PRL-3基因在肿瘤转移过程中的关键作用，发现下游信号因子；③对内质网紧张诱导的神经元凋亡进行分析；④运用干细胞移植治疗心肌坏死和促进新血管形成；⑤证明Notch信号传导调节血管重塑过程和抑制寡突胶质细胞分化；⑥发现干扰素抑制寡突胶质细胞凋亡；⑦发现p53和bcl-2基因对DNA损伤诱导细胞凋亡的调控作用及其对胚胎发育的影响。

代表论文：

A. Research papers (*Correspondence author)

1. Xiong X, Qi X, Ge XM, Gu P, Zhao J, Zhao QS, *Gao X.(2007) A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. J Biomed Sci, in press

2. Sha HB, Xu J, Tang J, Ding J, Gong JF, Ge XM, Kong D, *Gao X. (2007) Disruption of a novel regulatory locus results in decreased Bdnf expression, obesity and type 2 diabetes in mice. Physiological Genomics, in press

3. Qi X, Yang G, Yang L, Lan Y, Weng T, Wang J, Wu Z, Xu J, *Gao X, *Yang X. (2007)Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development. Dev Biol, in press

4. Zeng H, Di L, Fu GP, Chen YH, Gao X, Xu L, Lin X, Wen RR (2007) Phosphorylation of Bcl10 negatively regulates T cell receptor-mediated NF-kB activation. Mol Cell Biol, 27:5235-45

5. Liu X, Chen Y, Zhang F, Chen L, Ha T, Gao X, Li C. Synergistically therapeutic effects of VEGF165 and angiopoietin-1 on ischemic rat myocardium. Scand Cardiovasc J. 2007 Apr;41(2):95-101.

6. Hua F, Ha T, Ma J, Li Y, Kelley J, Gao X, Browder IW, Kao RL, Williams DL, Li C (2007) Protection against Myocardial Ischemia/Reperfusion Injury in TLR4-Deficient Mice Is Mediated through a Phosphoinositide 3-Kinase-Dependent Mechanism. J Immunol, 178:7317-24.

7. Liu L, Zhang X, Qian B, Min X, Gao X, Li C, Cheng Y, Huang J (2007) Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice. Eur J Heart Fail., in press

8. Tan X, Weng T, Zhang J, Wang J, Li W, Wan H, Lan Y, Cheng X, Hou N, Liu H, Ding J, Lin F, Yang R, Gao X, Chen D, Yang X（2007）Smad4 is required for maintaining normal murine postnatal bone homeostasis. J Cell Sci 120: 2162-2170;

9. Chen JY, Schopf JW, Bottjer DJ, Zhang CY, Kudryavtsev AB, Tripathi AB, Wang XQ, Yang YH, Gao X, Yang Y (2007) Raman spectra of a Lower Cambrian ctenophore embryo from southwestern Shaanxi, China. PNAS 104: 6289-6292;

10. Zhang D, Zhang F, Zhang Y, Gao X, Li C, Yang N, Cao K (2007) Combining erythropoietin infusion with intramyocardial delivery of bone marrow cells is more effective for cardiac repair. Transpl Int. 20:174-83.

11. Fan Y, Liu X, Zhang H, Dai J, Zhang X, Zhu M, Gao X, Wang Y (2006) Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population. Cancer Genet Cytogenet. 170:121-8.

12. Gu X, Xu F, Song W, Yang Y, Hu P, Wang X, Gao X, Zhao Q (2006) A novel cytochrome P450, zebrafish Cyp26D1, involved in metabolism of all-trans retinoic acid, Molecular Endocrinology, 20:1661-72.

13. Chen JY, Bottjer DJ, Davidson EH, Dornbos SQ, Gao X, Li CW, Yang YH, Li G, Wang XQ, Xian DC, Wu RH, Hwu YK (2006) Phosphatized polar-lobe-forming embryos from the Precambrian of southwest China. Science, 312: 1644-1646

14. Zhang D, Zhang F, Zhang Y, Gao X, Li C, Ma W, Cao K. (2006) Erythropoietin enhances the angiogenic potency of autologous bone marrow stromal cells in a rat model of myocardial Infarction. Cardiology. 108:228-236

15. Yu M, Sha H, Gao Y, Zeng H, Zhu M, Gao X* (2006) Alternative 3’ UTR polyadenylation of Bzw1 transcripts display differential translation efficiency and tissue-specific expression. Biochem Biophys Res Commun. 345:479-85

16. Yang CX, Chen HQ, Chen C, Yu WP, Zhang WC, Peng YJ, He WQ, Wei DM, Gao X, Zhu MS (2006) Microfilament-binding properties of N-terminal extension of the isoform of smooth muscle long myosin light chain kinase. Cell Res, 16:367-76

17. Zhu Y, Zeng H, Gao X, Lu ZH (2006) Quantitative analysis of EcoR1 methylase-DNA complex by atomic force microscopy. Scanning 28: 15-19

18. Ha T, Li Y, Gao X, McMullen JR, Shioi T, Izumo S, Kelley JL, Zhao A, Haddad GE, Williams DL, Browder IW, Kao RL, Li C. (2005) Attenuation of cardiac hypertrophy by inhibiting both mTOR and NFkB activation in vivo. Free Radical Biology & Medicine, 39:1570-80

19. Hua F, Ha T, Ma J, Gao X, Kelley J, Williams DL, Browder IW, Kao RL, Li C.(2005) Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts. Biochem Biophys Res Commun. 338:1118-25

20. Ha T, Hua F, Li Y, Ma J, Gao X, Kelley J, Zhao A, Haddad GE, Williams DL, Browder IW, Kao RL, Li C. (2005) Blockade of MyD88 Attenuates Cardiac Hypertrophy and Decreases Cardiac Myocyte Apoptosis in Pressure Overload Induced Cardiac Hypertrophy in vivo. Am J Physiol Heart Circ Physiol., 290(3):H985-94

21. Ha T, Li Y, Hua F, Ma J, Gao X, Kelley J, Zhao A, Haddad GE, Williams DL, William Browder I, Kao RL, Li C. (2005) Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload. Cardiovasc Res. 68:224-34.

22. Gu X, Xu F, Wang X, Gao X, Zhao Q. (2005) Molecular cloning and expression of a novel CYP26 gene (cyp26d1) during zebrafish early development. Gene Expr Patterns 5:733-9

23. Yang G, Cui F, Hou N, Chen X, Zhang J, Wang Y, Jiang N, Gao X, Yang X (2005) Transgenic Mice That Express Cre Recombinase in Differentiated Hypertrophic Chondrocytes, Genesis, 42:33-6

24. Ruan H, Zhang N, *Gao X (2005) Identification of a novel point mutation of mouse proto-oncogene c-kit through N-ethyl-N-nitrosourea (ENU) mutagenesis. Genetics, 169:819-31

25. Zhou L, Ma W, Yang Z, Zhang F, Lu L, Ding Z, Ding B, Ha T, *Gao X, *Li C. (2005)　VEGF(165) and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways. Gene Ther. 12:196-202

26. Wu X, Zeng H, Zhang X, Zhao Y, Sha H, *Gao X, *Xu Q. (2004) PRL-3 promotes motility and metastasis of mouse melanoma cells. Am J. Path. 164: 2039

27. Wen C, Xue B, Qin X, Yu M, Zhang M, Zhao D, Gao X, Gu J, Li C. (2004) NRAGE suppress cell proliferation though a p53 dependent pathway. FEBS Lett. 564: 171

28. Li C, Ha T, Gao X, Kelley J, Browder W, Williams DL. (2004) NFkB activation is required for the development of cardiac hypertrophy in vivo. Am J Phys: Heart and Circulatory Physiology. 287 : H1712

29. Li C, Ha T, Kelley J, Gao X, Qiu Y, Kao RL, Browder W, Williams DL. (2004) Modulating Toll-like receptor mediated signaling by (1-->3)-beta-d-glucan rapidly induces cardioprotection. Cardiovasc Res. 61:538

30. Zhu Y, Zheng H, Xie JM, Ba L, Gao X, Lu Z (2004) AFM studies on DNA structural changes induced by vincristine sulfate and aspirin. Microscopy and Microanalysis 10:286

31. Zhang F, Yang Z, Chen Y, Qin J, Zhu T, Xu D, Xu Z, Xu Q, Qian Y, Ma W, Chen L, Gao X, Li C, Ha T, Kao RL. (2003) Clinical cellular cardiomyoplasty: technical considerations. J Card Surg.18:268

32. He F, Wang Z, Zhao J, Bao J, Ding J, Ruan H, Xie Q, Zhang Z, *Gao X. (2003) Large- scale screening of disease model through ENU mutagenesis in mice. Chinese Science Bulletin. 24:2665

33. Kao RL, Zhang FM, Yiang ZJ, Gao X, Li CF (2003) Cellular cardiomyoplasty using autologous satellite cells: from experimental to clinical study. Basic Appl. Myol. 13:1

34. Zhang F, Chen Y, Yang Z, Gao X, Ma W, Li C, Kao RL (2003) Cellular cardiomyoplasty for a patient with heart failure. Cardiovascular Radiation Medicine 4: 43

35. Zhang F, Gao X, Yiang ZJ, Ma W, Li C, Kao RL (2003) Cellular cardiomyoplasty: A preliminary clinical report. Cardiovascular Radiation Medicine 4: 39

36. Jiang P, Chen L, Liu J, Ding J, Gao X and Guo ZJ (2002) Novel zinc fluorescent probe bearing dansyl and aminoquinoline groups. Chemical Communication 2002:1424

37. Chen LZ and *Gao X (2002), Neuronal apoptosis induced by endoplasmic reticulum stress. Neurochemical Research, 27:891

38. McCright B, Gao X, Shen L, Lozier J, Lan Y, Maguire M, Herzlinger D, Weimaster G, Jiang R and Gridley T. (2001) Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development, 128:491

39. Gao X, Gillig TA, Ye P, D’Ercole AJ, Matsushima GK and Popko B. (2000) Interferon-gamma protects against Cuprizone-induced demyelination. Mol & Cell Neurosci. 16:338-49

40. Xue Y, Gao X (co-first author), Lindsell CE, Norton CR, Chang B, Hicks C, Gendron-Maguire M, Rand EB, Weinmaster G and Gridley T (1999) Embryonic Lethality and vascular defects in mice lacking the Notch ligand Jagged 1. Hum Mol Genet 8:723-30

41. Gao X, Copeland NG, Gilbert DJ, Jenkins NA and Gridley T, (1998) Assignment of the murine Notch2 and Notch3 gense to chromosomes3 and 17. Genomics 49:60-1

42. Wubah JA,Ibrahim MM,Gao X, Pisano MM and Knudsen TB (1996) Teratogen-induced eye defect is mediated by p53-dependent embryonic apoptosis. Current Biology 6:60-9

43. Gao X, Knudsen TB, Ibrahim MM and Haldar S. (1995) Bcl-2 relieves deoxyadenylate stress and suppresses apoptosis in pre-B leukemia cells. Cell Death and Differentiation 2:69-77

44. Gao X, Blackburn MR and Knudsen TB. (1994) Activation of apoptosis by 2'-deoxyadenosine in mouse early postimplantation embryos. Teratology 49:1-12

45. Blackburn MR, Gao X, Airhart MJ, Skalko RG, Thompson LF, Knudsen TB. (1992) Adenosine levels in the postimplantation mouse uterus: quantitation by HPLC-fluorometric detection and spatiotemporal regulation by 5'-nucleotidase and adenosine deaminase. Dev Dyn. 194:155-68

46. Liu JN, Lu L, Gao X, Wang J, Zhu D, Lai LH, Xu XJ, Tang YQ. (1992) The structure basis of the poor fibrin specificity of urokinase (I)-knowledgebased prediction of Kringle structures of urokinase and its related proteins. Sci China, Series B, 35:176-82

47. 郑一守, 秦国强, 高翔, 刘杰, 丁琪, 张梅芬, 姚建华 (1986) 抗体形成细胞发育的免疫组织化学研究．实验生物学报，19 : 327—337

B.Books and reviews:

1. 高翔：小鼠ENU化学诱变和QTL分析在疾病研究中的应用，in 基因工程小鼠，p95-115，傅继梁主编，上海科学技术出版社

2．高翔，迟慧梅：生命的起源与进化，p92-97；高翔：生物技术在医学中的应用，p118-126，in 生物医学导论，吴观陵主编，人民卫生出版社

3．Gao X, Kemper A and Popko B. (1999) Advanced transgenic and gene-targeting approaches. Neurochem. Res. 24:1181-8

实验室成员：

技术员: 李瑶

研究生: 丁钧，阮海斌，赵静，任凯群，沙海波，熊熙文，唐晶，陈维倩，林兆宇，徐静悦，齐心，周玥，蒋璇，闫果林，陈辉，卢在恋，魏晓为，杨军。

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