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肿瘤学博导 胡继繁

hjf.JPG   胡继繁,教授,博士研究生导师,肿瘤中心基础研究室学术带头人。1992 美国康奈尔大学营养生物化学博士,在肿瘤和干细胞表观遗传学研究领域取得了诸多原创性成果,并发表在Science, Journal of Cell Biology, JCI, EMBO J, Hepatology, Oncogene等高水平杂志上。迄今,发表SCI源刊论著40余篇,其中第一或通讯作者论著20余篇,IF大于5共16篇,总被引频次大于500次;获得美国授权专利3项;研究方向为干细胞和表观遗传学,包括IGF2/H19基因印记机理以及表观遗传性状的修饰与癌症治疗;诱导多能干细胞(ips)重编程的表观遗传学机制等。

研究方向:

  1. 肿瘤表观遗传学研究:肿瘤遗传印记调控;染色体空间构象和肿瘤基因表达的关系;DNA甲基化/组蛋白修饰(甲基化、乙酰化)对肿瘤侵袭、迁移的影响。

  2. 干细胞重编程机制:染色体空间构象对体细胞重编程的调控研究;微环境对肿瘤干细胞定向分化的影响。

  3. 非编码RNA:非编码RNA对基因调控的机制研究;非编码RNA对基因的表观遗传学调控; 肿瘤相关的非编码RNA的筛选和其作用机制。

  4. 肿瘤基因治疗:肿瘤抗体基因靶向疗法;利用表观遗传机理修饰和抑制癌基因,达到肿瘤靶向治疗。

 

代表性课题

  1. RUNX1 长链非编码RNA在急性髓系白血病的作用及机制(国家自然科学基金项目#81272294)

  2. 诱导多能干细胞的高效重编程机制研究(吉林省科技发展计划国际科技合作项目)

  3. 优化重编程因子高效诱导个性化多能干细胞(美国California Institute of Regenerative Medicine (CIRM) grant #RT2-01942)

 

留学经历:

机构和位置                          学位           年份            学术领域

美国康奈尔大学                    Ph. D.        8/87-9/92         营养生物化学

美国康奈尔大学                   博士后         9/92-2/94         肿瘤营养调控

美国斯坦福大学                    博士后         2/94-2/96         肿瘤表观遗传调控

美国斯坦福大学医学院               研究助理       2/96-10/98        肿瘤表观遗传调控

美国斯坦福大学医学院               高级研究员     10/98-5/00        肿瘤表观遗传

美国斯坦福大学医学院               首席科学家     5/02-11/11        癌症和干细胞表观遗传

 

学术专著

  1. Hu JF, Parpia B, Campbell TC.  Dietary calcium and bone density of women in China.  In: Lau E, eds. Osteoporosis Research in Asia - Crossing the Frontiers.  World Scientific Publishing Co, 1997:57-9.

  2. Hu JF, Hoffman AR. Examination of Histone Acetylation at the Printed Loci, In: Ward A. ed. Genomic Imprinting: Methods and Protocols. The Human Press Inc., 2001:285-296.

 

期刊论文

  1. Hu JF*, Hoffman AR. Chromatin looping is needed for iPSC induction. Cell Cycle. 2014;13:1-2 (IF 5.2)

  2. Zhang H, Jiao W, Sun L, Fan J, Chen M, Wang H, Xu X, Shen A, Li T, Niu B, Ge S, Li W, Cui J, Wang G, Sun J, Fan X, Hu X, Mrsny RJ, Hoffman AR, Hu JF*. Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming. Cell Stem Cell 2013;13:30-35 (IF 25.32)

  3. Zhang H, Zeitz MJ, Wang H, Niu B, Ge S, Li W, Cui J, Wang G, Qian G, Higgins MJ, Fan X, Hoffman AR, Hu JF*. Long noncoding RNA-mediated intra-chromosomal interactions promote imprinting at the Kcnq1 locus. Journal of Cell Biology 2014;204:61-75 (IF 10.82)

  4. Zhang S, Zhong B, Chen M, Yang L, Yang G, Li Y, Wang G, Cui J, Li W, Hoffman AR, Hu JF*. Epigenetic reprogramming reverses the malignant epigenotype of the MMP/TIMP axis genes in tumor cells. Int J Cancer 2013 Sep 17. doi: 10.1002/ijc.28487. [Epub ahead of print] (IF 6.20)

  5. Li T, Chen H, Li W, Cui J, Wang G, Hu X, Hoffman AR, Hu JF*. Promoter histone H3K27 methylation in the control of IGF2 imprinting in human tumor cell lines. Hum Mol Genet  2014;23:117-128 (IF 7.69)

  6. Chen M, Zhang H, Wu J, Xu L, Xu D, Sun J, He Y, Zhou X, Wang Z, Wu L, Xu S, Wang J, Jiang S, Zhou X, Hoffman AR, Hu X, Hu JF*, Li T. Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway. Biomaterials 2012;33:5514-5523 (IF 7.60)

  7. Zhang H, Niu B, Hu JF*, Ge S, Wang H, Li T, Ling J, Steelman BN, Qian G, Hoffman AR.  Interruption of intrachromosomal looping by CTCF decoy proteins abrogates genomic imprinting of human insulin-like growth factor II. Journal of Cell Biology 2011;193:475-487 (IF 10.82)

  8. Ling JQ, Li T, Hu JF, Vu TH, Chen HL, Qiu XW, Cherry AM, Hoffman AR. CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science. 2006 312:269-272 (IF 31.03)

  9. Zhu XQ, Pan XH, Wang W, Chen Q, Pang RQ, Cai XM, Hoffman AR, Hu JF*. Transient in vitro epigenetic reprogramming of skin fibroblasts into multipotent cells. Biomaterials 2010;31:2779-87 (IF 7.60)

  10. Pan Y, He B, Lirong Z, Nie Z, Chen L, Gu L, Hoffman AR, Wang S, Hu JF*. Gene therapy for cancer through adenovirus vector‑mediated expression of the Ad5 early region gene 1A based on loss of IGF2 imprinting. Oncol Rep. 2013;30:1814-1822.

  11. Song W, Wang N, Li W, Wang G, Hu JF, He K, Li Y, Meng Y, Chen N, Wang S, Hu L, Xu B, Wang J, Li A, Cui J. Serum peptidomic profiling identifies a minimal residual disease detection and prognostic biomarker for patients with acute leukemia. Oncol Lett. 2013;6:1453-1460

  12. Wang H, Song X, Zhang H, Zhang J, Shen X, Zhou Y, Fan X, Dai L, Qian G, Hoffman AR, Hu JF*, Ge S, Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts. Int J Cancer 2012;130:443–453

  13. Nie ZL, Pan YQ, He BS, Gu L, Chen LP, Li R, Xu YQ, Gao TY, Song GQ, Hoffman AR, Wang SK, Hu JF*. Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system. Mol Cancer. 2012 ;11:86.

  14. Huang X, Wang L, Zhang H, Wang H, Zhao X, Qian G, Hu JF*, Ge S, Fan X. Therapeutic efficacy by targeting correction of Notch1-induced aberrants in uveal tumors. PLoS One. 2012;7:e44301

  15. Yao Y, Wang L, Zhang H, Wang H, Zhao X, Zhang Y, Zhang L, Fan X, Qian G, Hu JF*,Ge S. A Novel Anticancer Therapy That Simultaneously Targets Aberrant p53 and Notch Activities in Tumors. PLoS One. 2012;7:e46627

  16. Fan J, Zhou Y, Huang X, Zhang L, Yao Y, Song X, Chen J, Hu JF, Ge S, Song H, Fan X. The combination of polyalanine expansion mutation and a novel missense substitution in transcription factor FOXL2 leads to different ovarian phenotypes in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients. Hum Reprod. 2012;27:3347-57

  17. Liu F, Lu W, Qian Q, Qi W, Hu JH*, Feng B. Frequency of TLR 2, 4, and 9 Gene Polymorphisms in Chinese Population and Their Susceptibility to Type 2 Diabetes and Coronary Artery Disease. J Biomed Biotechnol. 2012;2012:1-7

  18. Zhang J, Huang S, Zhang H, Wang H, Guo H, Qian G, Fan X, Lu J, Hoffman AR, Hu JF*, Ge S, Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting Friend leukemia virus integration 1, Cancer 2011;117:86-95

  19. Azar WJ, Azar SH, Higgins S, Hu JF, Hoffman AR, Newgreen DF, Werther GA, Russo VC. IGFBP-2 enhances VEGF gene promoter activity and consequent promotion of angiogenesis by neuroblastoma cells. Endocrinology. 2011;152:3332-3342

  20. Feng B, Xu L, Wang H, Yan X, Xue J, Liu F, Hu JF*. Atorvastatin exerts its anti-atherosclerotic effects by targeting the receptor for advanced glycation end products. Biochim Biophys Acta- Molecular Basis of Disease. 2011;1812:1130-7

  21. Ma AN, Huang WL, Wu ZN, Hu JF, Li T, Zhou XJ, Wang YX. Induced epigenetic modifications of the promoter chromatin silence survivin and inhibit tumor growth. Biochem Biophys Res Commun. 2010;393:592-597

  22. Pan YQ, He BS, Li T, Zhu C, Zhang LR, Wang B, Xu YF, Qu LL,1 Hoffman AR, Wang SK, Hu JH*. Targeted tumor gene therapy based on loss of IGF2 imprinting. Cancer Biology & Therapy 2010;10;290-298

  23. Zhang J, Huang S, Zhang H, Wang H, Guo H, Qian G, Fan X, Lu J, Hoffman AR, Hu JF*, Ge S, Targeted knockdown of Bcl2 in tumor cells using a synthetic TRAIL 3’-UTR microRNA, Int J Cancer 2010;26:2229-2239

  24. Song X, Zhou Y, Jia R, Xu X, Wang H, Hu JH, Ge S, Fan X. Inhibition of retinoblastoma in vitro and in vivo with conditionally replicating oncolytic adenovirus H101. Invest Ophthalmol Vis Sci. 2010;51:2626-35

  25. Zhang H, Qian GX, Wang HB, Niu BB, Fan XQ, Lu J, Hoffman AR, Hu JF*, Ge SH. Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. Molecular Therapy, 2009;17:57-64

  26. Li T, Hu JF*, Qiu XW, Ling JQ, Chen HL, Wang SK, Hou AJ, Vu TH Hoffman AR. CTCF regulates allelic expression of Igf2 by orchestrating a promoter-polycomb repressive complex-2 intrachromosomal loop, Molecular Cell Biology 2008;28:6473-6482

  27. Zhang J, Huang S, Zhang H, Wang H, Guo H, Qian G, Fan X, Lu J, Hoffman AR, Hu JF*, Ge S, Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting Friend leukemia virus integration 1, Cancer 2011;117:86-95

  28. Zhang H, Qian GX, Wang HB, Niu BB, Fan XQ, Lu J, Hoffman AR, Hu JF*, Ge SH. Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. Molecular Therapy, 2009;17:57-64

  29. Zhang J, Huang S, Zhang H, Wang H, Guo H, Qian G, Fan X, Lu J, Hoffman AR, Hu JF*, Ge S, Targeted knockdown of Bcl2 in tumor cells using a synthetic TRAIL 3’-UTR microRNA, Int J Cancer 2010;26:2229-2239

  30. Chen HL, Li T, Wu J, Ling JQ, Sun ZH, Wang WB, Chen W, Qiu XW, Hou AJ, Vu TH, Hoffman AR, Hu JF*. Correction of aberrant imprinting of IGF2 in human tumors by nuclear transfer-induced epigenetic reprogramming. EMBO J, 2006;25: 5329-5338

  31. Hoffman AR, Hu JF. Directing DNA methylation to inhibit gene expression. Cell Mol Neurobiol. 2006;26: 425-438

  32. Yao XM, Hu JF, Daniels M, Zhou XJ, Yien HF, Lu HQ, Zeng ZL, Li T, Hoffman AR. The use of a methylated oligonucleotide to inhibit IGF2 gene expression and to enhance survival in a model of hepatocellular carcinoma.  Journal of Clinical Investigation 2003:111: 265-273

  33. Yao XM, Hu JF*, Daniels M, Yien  HF, Lu HQ, Sharan H, Li T, Vu TH, Hoffman AR. A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis. Clinical Cancer Research 2003, 9:2719-2726

  34. Yao XM, Hu JF*, Li T, Yang Y, Sun Z, Ulaner G, Vu TH, and Hoffman AR.  Epigenetic regulation of the taxol-resistance associated gene TRAG-3 in human tumors. Cancer Genetics & Cytogenetics 2004;151:1-13

  35. Yang XM, Hu JF*, Ulaner GA, Li T, Yao X, Vu TH, and Hoffman AR.  Epigenetic Regulation of Igf2/H19 imprinting at CTCF insulator binding sites.  J Cell Biochem 2003; 90:1038-1055 

  36. Ulaner GA, Yang Y, Hu JF, Li T, Vu TH, Hoffman AR. CTCF Binding at the Insulin-Like Growth Factor-II (IGF2)/H19 Imprinting Control Region Is Insufficient to Regulate IGF2/H19 Expression in Human Tissues. Endocrinology. 2003;144:4420-4426

  37. Ulaner GA, Hu JF, Vu TH, Giudice LC, Hoffman AR.  Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development. Int J Cancer 2001;91:644-9

  38. Hoffman AR, Vu TH, Hu JF.  Mechanisms of genomic imprinting.  Growth Horm IGF Res 2000;10:S18

  39. Hu JF, Pham J, Dey N, Li T, Vu TH, and Hoffman AR. Allele-Specific Histone Acetylation Accompanies Genomic Imprinting of the Insulin-like Growth Factor II Receptor Gene. Endocrinology 2000;141:4428-4435

  40. Hu JF, Ulaner GA, Oruganti H, Vu TH, Hoffman AR. Allelic expression of the putative tumor suppressor gene p73 in human tumor speciemns and fetal tissues. Biochemica et Biophysica Acta 2000;1491:49-56

  41. Ulaner GA, Hu JF, Vu TH, Oruganti H, Giudice LC, Hoffman AR. Regulation of telomerase by alternate splicing of human telomerase reverse transcriptase (hTERT) in normal and neoplastic ovary, endometrium, and myometrium. Int J Cancer. 2000;85:330-335

  42. Hu JF, Balaguru KA, Ivaturi RD, Oruganti H, Li T, Nguyen BT, Vu TH, Hoffman AR.  Lack of reciprocal genomic imprinting of sense and antisense RNA of mouse insulin-like growth factor II receptor in the central nervous system. Biochem Biophys Res Commun. 1999;257:604-608

  43. Root MM, Hu JH, Stephenson LS, Parker RS, Campbell TC. Iron status of middle-aged women in five counties of rural China. Eur J Clin Nutr. 1999;53:199-206

  44. Root MM, Hu JH, Stephenson LS, Parker RS,Campbell TC. Determinants of plasma retinol concentrations of middle-aged women in rural China. Nutrition. 1999;15:101-7

  45. Hu JF, Oruganti H, Vu TH, Hoffman AR.  The role of histone acetylation in the allelic expression of the imprinted human insulin-like growth factor II gene. Biochem Biophys Res Commun. 1998;20;251:403-408

  46. Hu JF, Oruganti H, Vu T, Hoffman AR. Tissue-specific imprinting of the mouse insulin-like growth factor II receptor gene correlates with differential allele-specific DNA methylation.  Molecular Endocrinology  1998;12:220-2

  47. Hu JF, Nguyen PH, Vu T, Hoffman AR.  Modulation of Genomic imprinting of IGF2 and H19 in mice by inhibitors of DNA methylation.  Molecular Endocrinology 1997;11:1891-1898

  48. Hu JF, Vu T, Hoffman AR.  Genomic deletion of a putative imprinting element abolishes imprinting of insulin-like growth factor IIJ Biol Chem 1997;272:20715-20720

  49. Hu JF*, Cheng ZC, Chisari FV, Vu TH, Hoffman AR, Campbell TC.  Repression of hepatitis B virus (HBV) transgene and HBV-induced liver injury by low protein diet.  Oncogene 1997;15:2795-2801

  50. Cheng ZC, Hu JF, Chisari FV, Jay G, Campbell TC.  Inhibition of hepatocellular carcinoma development in hepatitis B virus transfected mice by low dietary casein. Hepatology 1997;26:1351-54

  51.  Hu JF, Vu T, Hoffman AR.  Promoter-specific modulation of insulin-like growth factor II by inhibitors of DNA methylation.  J Biol Chem  1996;271:18253-18262

  52. Hu JF, Vu T, Hoffman AR.  Differential biallelic activation of three insulin-like growth factor II promoters in the mouse central nervous system,  Molecular Endocrinology 1995;9:628-636

  53. Hu JF*, Zhao XH, Parpia B, Chen JS, and Campbell TC.  Assessment of a modified household food weighing method in a study of bone health in China.  Eur J Clin Nutr  1994;48:442-452

  54. Hu JF*, Zhao XH, Parpia B, Chen JS, and Campbell TC.  Bone density and lifestyle characteristics in pre- and postmenopausal Chinese women.  Osteoporosis International  1994;4:288-297

  55. Hu JF*, Zhao XH, Parpia B, and Campbell TC.  Dietary intakes and urinary excretion of calcium and acids: a cross-sectional study of women in China.  Am J Clin Nutr  1993;58:398-406

  56. Hu JF*, Zhao XH, Jia JB, Parpia B, and Campbell TC.  Dietary calcium and bone density among middle-aged and elderly women in China.  Am J Clin Nutr 1993;58:219-27

 

* Corresponding author (通讯作者)

IF = SCI impact factor (SCI收录期刊影响因子)