高翔
高翔 PhD
教育部长江计划特聘教授，博士生导师
南京大学模式动物研究所所长
 |
| 高翔 |
教育部长江计划特聘教授，博士生导师
南京大学模式动物研究所所长
办公室：58641510
实验室：58641511
电子邮件:gaoxiang@nju.edu.cn
1985年毕业于南京大学生物系，获学士学位
1988年毕业于南京大学生物化学系，获硕士学位
1994年毕业于美国Thomas Jefferson University发育与解剖学系，获发育学博士学位，
1988.07-1989.11 东南大学生物医学工程系,助教
1994.05-1995.12 Roche Institute of Molecular Biology, 博士后
1995.12-1997.02 The Jackson Laboratory, 博士后
1997.03-2000.03 Neuroscience Center, University of North Carolina at
Chapel Hill,Research Associate
2000.03- 南京大学，教授，博士生导师
2002.12- 南京大学模式动物研究所所长
中国遗传学会动物遗传学委员会副主任委员
中国实验动物学会常务理事
中国细胞生物学会理事
江苏省发育生物学会副理事长
江苏省动物学会理事
国家自然科学基金会评委
全国科学技术名词审定委员会第二届遗传学名词审定委员会委员
研究方向
主要研究方向利用基因组改造技术，建立复杂疾病小鼠模型，分析疾病表型的分子机理。实验室已建立了多种糖尿病／肥胖症模型、心脏病模型。这些模型证实了疾病相关基因的功能调控的多层次复杂性：包括BDNF转录的远程调控，蛋白水平修饰（Pax6突变对PC2蛋白酶影响）和蛋白磷酸化调控（PP2A基因剔除、c-Kit突变）等。非转录的基因组保守序列功能分析也是本实验室的工作重点。
2001-2004: “Establishing The National Research Center of Mutant Mice”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 50,000,000 RMB (Equal to 6 million USD)
The major goal of this project is to set up the national mouse research center with up-to-date transgenic facilities and standardize mouse research protocols. Funding also covers various research projects related to disease model.
2002-2004: “Large Scale Screening of Mutant Mice by ENU Mutagenesis”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Sci. and Tech. of China, Direct Cost: 390,000 RMB
The major goal of this project is to screen mutant mice with neurological phenotypes with ENU mutagenesis.
2002-2004, “Gene Expression Profile Analysis of Diabetic Mouse Kidney with Microarray”, PI: Xiang Gao, Ph.D.
Agency: Department of Science & Technology of Jiangsu, Direct Cost: 200,000 RMB
The major goal of this project is to elucidate the genetic control of vascular pathogenesis in kidney of diabetes mellitus.
2002-2003, “Phenotyping of Several Mouse Disease Models”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 1,550,000 RMB
The major goal of this project is to characterize 25 lines of mutant mice related to metabolic disease.
2003-2004, “Establishment of the Database Platform for Mouse Bioinformatics in China”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 2,000,000 RMB
The major goal of this project is to establish a web based database for mouse genetics research.
2003-2005,“PRL-3 signaling in tumor metastasis” PI: Xiang Gao, Ph.D.
Agency: Ministry of Education of China, Direct Cost: 200,000 RMB
The major goal of this project is to study the role and signaling of PRL-3 during tumorigenesis.
2004-2006: “Functions of TLR signaling in cardiac hypertrophy development modulation”, PI: Xiang Gao, Ph.D.
Agency: National Natural Science Foundation of China, Direct Cost: 200,000 RMB
The goal is to elucidate the TLR pathway mediated mechanisms of cardiac hypertrophy with mouse model.
2005-2007: “Vascular molecular biology based drug discovery and development”, Co-PI: Xiang Gao, Ph.D.
Agency: Ministry of Education of China, Direct Cost to Dr.Gao’s Lab: 1,000,000 RMB
The goal is to establish transgenic and KO mice models for vascular Biology Research.
2005-2009: “Generating and screening mouse mutant with congenital heart diseases” PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 2,500,000 RMB
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。
1. Masuda K, Ouchida R, Li YQ, Gao X, Mori H, Wang JY (2009) A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during immunoglobulin gene hypermutation. J Immunol. in press
2. Wang ZJ, Zhang FM, Wang LS, Yao Y, Zhao Q, Gao X (2009) Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biol Int. 33:665-74
3. Zheng Y, Xia Y, Hawke D, Halle M, Tremblay M, Gao X, Zhou X, Aldape K, Cobb M, Xie K, He J, and Lu Z (2009) FAK phosphorylation by ERK primes Ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST. Mol Cell. in press
4. Zhao J, Ding J, Li YQ, Ren KQ, Sha JH, Zhu MS, *Gao X (2009) HnRNP U mediates the long-range regulation of Shh expression during limb development. Hum Mol Genet. in press
5. Wang Q, Jiang L, Wang J, Li S, Yu Y, You J, Zeng R, Gao X, Rui L, Li W, Liu Y (2009) Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. Hepatology. In press
6. Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, *Gao X, *He L (2009) Sclerostin mediates bone response to mechanical unloading via antagonizing Wnt/b-catenin signaling. J Bone Miner Res, in press
7. Ding J, Gao Y, Zhao J, Yan H, Guo SY, Zhang QX, Li LS, *Gao X（2009）Pax6 haploinsufficiency causes abnormal metabolic homeostasis by down-regulating GLP-1 in mice. Endocrinology, in press
8. Wen JH, Chen YY, Song SJ, Ding J, Gao Y, Hu QK, Feng RP, Liu YZ, Ren GC, Zhang CY, Hong TP, *Gao X, and *Li LS (2009) Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3). Diabetologia, 52:504-13
9. Wang X, Zhang Y, Xiao G, Gao X, Liu XL (2009) c-Fos enhances survival of thymocytes during positive selection by upregulating Bcl-2. Cell Res. 19:340-7
10. Liu ZP, Zhang CL, Li Y, Wu ZY, Qian F, Yang XL, He WJ, Gao X, Guo Z (2009) A Zn2+ fluorescent sensor derived from 2-(pyridin-2-yl)benzoimidazole with ratiometric sensing potential. Organic letters 11:795-8
11. Qian F, Zhang CL, Zhang Y, He WJ, Gao X, Hu P, Guo ZJ (2009) Visible light excitable Zn2+ fluorescent sensor derived from an intramolecular charge transfer fluorophore and its in vitro and in vivo application. Journal of the American Chemical Society 131:1460-8
12. Zhang YF, Li H, Wang XM, Gao X, Liu XL (2009) Regulation of T cell development and activation by creatine kinase B. PLoS ONE 4:e5000
13. Chen H, Jin H, Du CY, Gu PY, Wang CY, Zhang QX, Gao X（2008）Establishment of transgenic mice expressing SV40T in parietal cells. Acta Anatomica Sinica 39: 699-702
14. Ding XF, Luo C, Ren KQ, Zhang J, Zhou JL, Hu X, Liu RS, Wang Y, *Gao X, *Zhang J (2008) Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions. DNA and Cell Biology 27: 257-265
15. Ha TZ, Hua F, Liu X, Ma J, McMullen JR, Shioi T, Izumo S, Kelley J, Gao X, Browder W, Williams DL, Kao RL, Li CF (2008) Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovascular Research 78:546-53
16. Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, Wen R (2008)TCR-mediated activation of CD4+CD44hi T cells bypasses Bcl10： An implication of differential NF-κB dependence of na?ve and memory T cells during TCR-mediated responses. J Biol Chem, 283:24392-9
17. Wang XM, Xiao G, Zhang YF, Wen XM, Gao X, Okada S, Liu X (2008) Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition Nature Immunology, 9:794-801
18. He WQ, Peng YJ, Zhang WC, Lv N, Tang J, Chen C, Zhang CH, Gao S, Chen HQ, Zhi G, Feil R, Kamm KE, Stull JT, *Gao X, *Zhu MS (2008) Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology, 135:610-20.
19. Liang D, Zhang M, Bao J, Zhang L, Xu X, Gao X, Zhao QS (2008) Expressions of Raldh3 and Raldh4 during zebrafish early development. Gene Expression Pattern, 8:248-53
20. Xiong X, Qi X, Ge XM, Gu P, Zhao J, Zhao QS, *Gao X.(2008) A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. J Biomed Sci, 15:47-59
21. Sun L, Ma K, Wang H, Xiao F, Gao Y, Zhang W, Wang K, Gao X, Ip N and Wu Z (2007) JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts. J Cell Biol. 179: 129-138
22. 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, 31:252-63
23. 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, 311:136-46
24. 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
25. Fan, Y., Wang, W., Zhu, M., Zhou, J., Peng, J., Xu, L., Hua, Z., Gao X, Wang, Y. (2007) Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer. Clinical Cancer Research 13 : 7515-7521
26. Yang, Y., Zheng, J., Zhou, X., Yang, Z., Tan, Y., Liu, A., Gao, X., Chang Z, Sheng, H.Z. (2007) Potential treatment of liver-related disorders with in vitro expanded human liver precursors. Differentiation 75 : 928-938
27. 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.
28. 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.
29. 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
30. 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;
31. 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;
32. 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.
33. 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.
34. 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.
35. 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
36. 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
37. 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
38. 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
39. Zhu Y, Zeng H, Gao X, Lu ZH (2006) Quantitative analysis of EcoR1 methylase-DNA complex by atomic force microscopy. Scanning 28: 15-19
40. 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
41. 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
42. 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
43. 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.
44. 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
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. 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
55. 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
56. 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
57. Zhang F, Gao X, Yiang ZJ, Ma W, Li C, Kao RL (2003) Cellular cardiomyoplasty: A preliminary clinical report. Cardiovascular Radiation Medicine 4: 39
58. 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
59. Chen LZ and *Gao X (2002), Neuronal apoptosis induced by endoplasmic reticulum stress. Neurochemical Research, 27:891
60. 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
61. 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
62. 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
63. 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
64. 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
65. 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
66. Gao X, Blackburn MR and Knudsen TB. (1994) Activation of apoptosis by 2'-deoxyadenosine in mouse early postimplantation embryos. Teratology 49:1-12
67. 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
68. 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
69. 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:
70.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
71．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
72．Gao X, Kemper A and Popko B. (1999) Advanced transgenic and gene-targeting approaches. Neurochem. Res. 24:1181-8
实验室：58641511
电子邮件:gaoxiang@nju.edu.cn
学习经历
1985年毕业于南京大学生物系，获学士学位
1988年毕业于南京大学生物化学系，获硕士学位
1994年毕业于美国Thomas Jefferson University发育与解剖学系，获发育学博士学位，
研究经历
1988.07-1989.11 东南大学生物医学工程系,助教
1994.05-1995.12 Roche Institute of Molecular Biology, 博士后
1995.12-1997.02 The Jackson Laboratory, 博士后
1997.03-2000.03 Neuroscience Center, University of North Carolina at
Chapel Hill,Research Associate
2000.03- 南京大学，教授，博士生导师
2002.12- 南京大学模式动物研究所所长
学术职务
中国遗传学会动物遗传学委员会副主任委员
中国实验动物学会常务理事
中国细胞生物学会理事
江苏省发育生物学会副理事长
江苏省动物学会理事
国家自然科学基金会评委
全国科学技术名词审定委员会第二届遗传学名词审定委员会委员
研究方向
主要研究方向利用基因组改造技术，建立复杂疾病小鼠模型，分析疾病表型的分子机理。实验室已建立了多种糖尿病／肥胖症模型、心脏病模型。这些模型证实了疾病相关基因的功能调控的多层次复杂性：包括BDNF转录的远程调控，蛋白水平修饰（Pax6突变对PC2蛋白酶影响）和蛋白磷酸化调控（PP2A基因剔除、c-Kit突变）等。非转录的基因组保守序列功能分析也是本实验室的工作重点。
承担项目
2001-2004: “Establishing The National Research Center of Mutant Mice”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 50,000,000 RMB (Equal to 6 million USD)
The major goal of this project is to set up the national mouse research center with up-to-date transgenic facilities and standardize mouse research protocols. Funding also covers various research projects related to disease model.
2002-2004: “Large Scale Screening of Mutant Mice by ENU Mutagenesis”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Sci. and Tech. of China, Direct Cost: 390,000 RMB
The major goal of this project is to screen mutant mice with neurological phenotypes with ENU mutagenesis.
2002-2004, “Gene Expression Profile Analysis of Diabetic Mouse Kidney with Microarray”, PI: Xiang Gao, Ph.D.
Agency: Department of Science & Technology of Jiangsu, Direct Cost: 200,000 RMB
The major goal of this project is to elucidate the genetic control of vascular pathogenesis in kidney of diabetes mellitus.
2002-2003, “Phenotyping of Several Mouse Disease Models”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 1,550,000 RMB
The major goal of this project is to characterize 25 lines of mutant mice related to metabolic disease.
2003-2004, “Establishment of the Database Platform for Mouse Bioinformatics in China”, PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 2,000,000 RMB
The major goal of this project is to establish a web based database for mouse genetics research.
2003-2005,“PRL-3 signaling in tumor metastasis” PI: Xiang Gao, Ph.D.
Agency: Ministry of Education of China, Direct Cost: 200,000 RMB
The major goal of this project is to study the role and signaling of PRL-3 during tumorigenesis.
2004-2006: “Functions of TLR signaling in cardiac hypertrophy development modulation”, PI: Xiang Gao, Ph.D.
Agency: National Natural Science Foundation of China, Direct Cost: 200,000 RMB
The goal is to elucidate the TLR pathway mediated mechanisms of cardiac hypertrophy with mouse model.
2005-2007: “Vascular molecular biology based drug discovery and development”, Co-PI: Xiang Gao, Ph.D.
Agency: Ministry of Education of China, Direct Cost to Dr.Gao’s Lab: 1,000,000 RMB
The goal is to establish transgenic and KO mice models for vascular Biology Research.
2005-2009: “Generating and screening mouse mutant with congenital heart diseases” PI: Xiang Gao, Ph.D.
Agency: Ministry of Science and Technology of China, Direct Cost: 2,500,000 RMB
研究成果
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。
论文著作
1. Masuda K, Ouchida R, Li YQ, Gao X, Mori H, Wang JY (2009) A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during immunoglobulin gene hypermutation. J Immunol. in press
2. Wang ZJ, Zhang FM, Wang LS, Yao Y, Zhao Q, Gao X (2009) Lipopolysaccharides can protect mesenchymal stem cells (MSCs) from oxidative stress-induced apoptosis and enhance proliferation of MSCs via Toll-like receptor(TLR)-4 and PI3K/Akt. Cell Biol Int. 33:665-74
3. Zheng Y, Xia Y, Hawke D, Halle M, Tremblay M, Gao X, Zhou X, Aldape K, Cobb M, Xie K, He J, and Lu Z (2009) FAK phosphorylation by ERK primes Ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST. Mol Cell. in press
4. Zhao J, Ding J, Li YQ, Ren KQ, Sha JH, Zhu MS, *Gao X (2009) HnRNP U mediates the long-range regulation of Shh expression during limb development. Hum Mol Genet. in press
5. Wang Q, Jiang L, Wang J, Li S, Yu Y, You J, Zeng R, Gao X, Rui L, Li W, Liu Y (2009) Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice. Hepatology. In press
6. Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, *Gao X, *He L (2009) Sclerostin mediates bone response to mechanical unloading via antagonizing Wnt/b-catenin signaling. J Bone Miner Res, in press
7. Ding J, Gao Y, Zhao J, Yan H, Guo SY, Zhang QX, Li LS, *Gao X（2009）Pax6 haploinsufficiency causes abnormal metabolic homeostasis by down-regulating GLP-1 in mice. Endocrinology, in press
8. Wen JH, Chen YY, Song SJ, Ding J, Gao Y, Hu QK, Feng RP, Liu YZ, Ren GC, Zhang CY, Hong TP, *Gao X, and *Li LS (2009) Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3). Diabetologia, 52:504-13
9. Wang X, Zhang Y, Xiao G, Gao X, Liu XL (2009) c-Fos enhances survival of thymocytes during positive selection by upregulating Bcl-2. Cell Res. 19:340-7
10. Liu ZP, Zhang CL, Li Y, Wu ZY, Qian F, Yang XL, He WJ, Gao X, Guo Z (2009) A Zn2+ fluorescent sensor derived from 2-(pyridin-2-yl)benzoimidazole with ratiometric sensing potential. Organic letters 11:795-8
11. Qian F, Zhang CL, Zhang Y, He WJ, Gao X, Hu P, Guo ZJ (2009) Visible light excitable Zn2+ fluorescent sensor derived from an intramolecular charge transfer fluorophore and its in vitro and in vivo application. Journal of the American Chemical Society 131:1460-8
12. Zhang YF, Li H, Wang XM, Gao X, Liu XL (2009) Regulation of T cell development and activation by creatine kinase B. PLoS ONE 4:e5000
13. Chen H, Jin H, Du CY, Gu PY, Wang CY, Zhang QX, Gao X（2008）Establishment of transgenic mice expressing SV40T in parietal cells. Acta Anatomica Sinica 39: 699-702
14. Ding XF, Luo C, Ren KQ, Zhang J, Zhou JL, Hu X, Liu RS, Wang Y, *Gao X, *Zhang J (2008) Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions. DNA and Cell Biology 27: 257-265
15. Ha TZ, Hua F, Liu X, Ma J, McMullen JR, Shioi T, Izumo S, Kelley J, Gao X, Browder W, Williams DL, Kao RL, Li CF (2008) Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovascular Research 78:546-53
16. Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, Wen R (2008)TCR-mediated activation of CD4+CD44hi T cells bypasses Bcl10： An implication of differential NF-κB dependence of na?ve and memory T cells during TCR-mediated responses. J Biol Chem, 283:24392-9
17. Wang XM, Xiao G, Zhang YF, Wen XM, Gao X, Okada S, Liu X (2008) Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition Nature Immunology, 9:794-801
18. He WQ, Peng YJ, Zhang WC, Lv N, Tang J, Chen C, Zhang CH, Gao S, Chen HQ, Zhi G, Feil R, Kamm KE, Stull JT, *Gao X, *Zhu MS (2008) Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology, 135:610-20.
19. Liang D, Zhang M, Bao J, Zhang L, Xu X, Gao X, Zhao QS (2008) Expressions of Raldh3 and Raldh4 during zebrafish early development. Gene Expression Pattern, 8:248-53
20. Xiong X, Qi X, Ge XM, Gu P, Zhao J, Zhao QS, *Gao X.(2008) A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. J Biomed Sci, 15:47-59
21. Sun L, Ma K, Wang H, Xiao F, Gao Y, Zhang W, Wang K, Gao X, Ip N and Wu Z (2007) JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts. J Cell Biol. 179: 129-138
22. 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, 31:252-63
23. 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, 311:136-46
24. 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
25. Fan, Y., Wang, W., Zhu, M., Zhou, J., Peng, J., Xu, L., Hua, Z., Gao X, Wang, Y. (2007) Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer. Clinical Cancer Research 13 : 7515-7521
26. Yang, Y., Zheng, J., Zhou, X., Yang, Z., Tan, Y., Liu, A., Gao, X., Chang Z, Sheng, H.Z. (2007) Potential treatment of liver-related disorders with in vitro expanded human liver precursors. Differentiation 75 : 928-938
27. 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.
28. 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.
29. 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
30. 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;
31. 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;
32. 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.
33. 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.
34. 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.
35. 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
36. 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
37. 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
38. 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
39. Zhu Y, Zeng H, Gao X, Lu ZH (2006) Quantitative analysis of EcoR1 methylase-DNA complex by atomic force microscopy. Scanning 28: 15-19
40. 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
41. 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
42. 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
43. 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.
44. 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
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. 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
55. 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
56. 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
57. Zhang F, Gao X, Yiang ZJ, Ma W, Li C, Kao RL (2003) Cellular cardiomyoplasty: A preliminary clinical report. Cardiovascular Radiation Medicine 4: 39
58. 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
59. Chen LZ and *Gao X (2002), Neuronal apoptosis induced by endoplasmic reticulum stress. Neurochemical Research, 27:891
60. 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
61. 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
62. 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
63. 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
64. 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
65. 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
66. Gao X, Blackburn MR and Knudsen TB. (1994) Activation of apoptosis by 2'-deoxyadenosine in mouse early postimplantation embryos. Teratology 49:1-12
67. 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
68. 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
69. 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:
70.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
71．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
72．Gao X, Kemper A and Popko B. (1999) Advanced transgenic and gene-targeting approaches. Neurochem. Res. 24:1181-8
附件列表
词条内容仅供参考，如果您需要解决具体问题
（尤其在法律、医学等领域），建议您咨询相关领域专业人士。