翁傑敏

翁傑敏，男，1964年3 月17日出生，華東師範大學生命醫學研究所副所長，生物化學學科教授，主要研究方向：表觀遺傳學，細胞核受體和腫瘤 。翁傑敏和妻子李紀文是華東師範大學生命科學學院生命醫學研究所的雙職工，兩人長期堅守教育科研崗位，自 1989 年赴美國留學至 2007 年，在生物醫學領域取得了一定的成績。回國後夫婦兩人到我校工作，，在生活中夫婦兩人更是攜手共進，以身作則教育子女尊老愛幼，共建了一個溫馨幸福的家庭。

基本介紹

• 中文名：翁傑敏
• 國籍：中國
• 出生日期：1964年3 月17日
• 職業：華東師範大學生命醫學研究所副所長
• 研究方向：表觀遺傳學
• 性別：男

個人履歷

1980.9-1984.7 武漢大學生物系 大學本科

翁傑敏和妻子李紀文

1984.9-1987.7 中科院上海細胞生物學研究所 碩士

1984.9-1994.3 The University of Vermont, USA 博士

1994.3-1997.7 National Institute of Health, USA 博士後

1997.8-2003.4 Assistant Professor, The Department of Molecular and Cellular Biology,

Baylor College of Medicine, Houston, Texas, USA

2003.4-2007.4 Associate Professor, The Department of Molecular and Cellular Biology,

Baylor College of Medicine, Houston, Texas, USA

2007.4- 華東師範大學生命科學學院，生物醫學研究所教授

研究方向

翁傑敏實驗室主要從事三個方面的研究工作。

第一是組蛋白化學修飾及其在基因表達中的作用。目前主要研究內容包括：（1）組蛋白甲基化是如何建立和去除的。（2）組蛋白化學修飾的信息是如何傳遞和解讀的。（3）組蛋白化學修飾在維持幹細胞功能中如何起作用的。我們首次報告了在組蛋白H3 9號位賴氨酸甲基化甲狀腺激素受體調控基因表達中的作用。我們還研究了H3 9號位賴氨酸甲基化抑制基因表達的作用機制。另外，我們也探索了9號賴氨酸甲基化的信息是如何解讀的。我們發現並鑑定了一個新的9號賴氨酸甲基化識別蛋白，並證明了這一蛋白在異質染色體的形成或維持中起重要作用。這些研究不僅奠定了我們在組蛋白修飾方向的工作基礎，也為我們最近開展的幹細胞表觀遺傳學研究提供了良好的技術平台。
第二是細胞激素受體調控基因表達的分子機制。細胞核激素受體在胚胎髮育、個體生長和發育、代謝、內分泌調控和癌變等多方面起著重要作用。一般而言，這些眾多的生物學功能主要是通過其對靶基因表達調控而實現的。這方面主要的研究內容包括核激素受體共激活蛋白(coactivator)的結構功能和作用機制，共阻抑蛋白(corepressor)的作用機制和生物學功能。我們首次分離純化了共阻抑蛋白SMRT/N-CoR複合體，並闡明了HDAC3在介導 SMRT/N-CoR轉錄抑制功能中的重要作用。另外我們最近發現了一個新的雄性激素受體共激活蛋白，這個共激活蛋白能特異促進雄性激素受體DNA結合能力。初步的研究表明這一蛋白在大部分前列腺癌樣品中有過量表達，因此有望成為一個新的前列腺癌的分子標記物和治療靶標。
第三個研究方向是人工誘導全能幹細胞。全能胚胎幹細胞在再生醫學和疾病治療上具有廣闊的前景，然而其套用卻受到來源及倫理的制約。我們將研究直接用蛋白質轉染細胞的方法誘導產生全能幹細胞的可能性。

研究課題

a．組蛋白修飾和核小體改造對染色質結構和功能的調控

b. 組蛋白密碼識別蛋白的鑑定和分子機制

c．組蛋白修飾的獨特形式在幹細胞更新、細胞分化和腫瘤發生等生理和病理過程中的重要作用

d．以雄性激素受體作為模型，研究基因表達的基本機制

e. 雄性激素受體共激活蛋白（coactivators）在前列腺癌中的作用。

f．共阻抑蛋白N-CoR/SMRT 複合體的作用機制和生理和病理功能

代表論文

(選自65篇SCI 文章)

1. Chen, H.B.,Wong, J., Jiang, K. and Bao, J.S. 1990. A new method for the synthesis of a structural gene. Nucleic Acid Research 18, 871-878.

2.Wong, J., Liu, F., and Bateman. E. 1992. Isolation of genomic DNA encoding transcription factor TFIID from Acanthamoeba castellanii:: characterization of the promoter. Nucleic Acids Res. 20, 4817-4826.

3. Radebaugh, C.A., Matthews, J. L., Geiss, G. K., Liu, F.,Wong, J., Bateman, E., Camier, S., Sentenac, A. and Paule, M. R. 1994. TATA-box binding protein (TBP) is a constituent of the polymerase I-specific transcription initiation factor TIF-IB (SL1) bound to the rRNA promoter and shows differential sensitivity to TBP-directed reagents in polymerase I, II, and III transcription factors. Mol. Cell. Biol. 14, 597-605.

4.Wong, J.and Bateman, E. 1994. TBP-DNA interactions in the minor groove discriminate between A:T and T:A base pairs. Nucleic Acids Res. 22, 1890-1896.

5. Ranjan, M.,Wong, J. and Shi, Y-B. 1994. Transcriptional repression of Xenopus TR gene is mediated by a thyroid hormone response element located near the start site. J. Biol. Chem. 269, 24699-24705.

6.Wong, J., Shi, Y-B. and Wolffe, A.P. 1995. A role of nucleosome assembly in the transcriptional regulation of Xenopus TRA gene by thyroid hormone receptor. Gene & Development. 9, 2696-2711.

7.Wong, J. and Shi, Y-B. 1995. Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors. J. Biol. Chem. 270, 18479-18483.

8.Wong, J., Shi, Y-B., and Wolffe, A.P. 1997. Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: hormone-regulated chromatin disruption is not sufficient for transcriptional activation. EMBO J. 16(11): 3158-3171.

9.Wong, J., Li, Q., Levi, B-Z., Shi, Y-B., and Wolffe, A.P. 1997. Structural and functional features of a specific nucleosome containing a recognition element for the thyroid hormone receptor. EMBO J. 16(23): 7130-7145.

10.Wong, J., Patterton, D., Imhof, A., Guschin, D., Shi, Y-B., and Wolffe AP. 1998. Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylase. EMBO J. 17(2): 520-534.

12.Wong J., Liang, V.C., Sachs, L.M., and Shi, Y.B. 1998. Transcription from the thyroid hormone-dependent promoter of the Xenopus laevis thyroid hormone receptor betaA gene requires a novel upstream element and the initiator, but not a TATA Box. J Biol Chem 273:14186-93.

13. Xue, Y.,Wong, J., Moreno, G.T., Young, M.A., Cote, J., and Wang, W. 1998. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Molecular Cell 2: 851-861.

14. Lanz, R. B., Mckenna, N.J., Onate, S.A., Albrecht, U.,Wong, J., Tsai, S.Y., Tsai, M-J. and O’Malley B.W. 1999. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97: 17-27.

15. Liu, Z.,Wong, J., Tsai, S.Y., Tsai, M-J and O’Malley B.W. 1999. Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell free transcription of chromatin. PNAS 96: 9485-9490.

16. Li, J., O’Malley B.W andWong J. 2000. p300 requires its HAT activity and SRC-1 interaction motif to facilitate TR activation in chromatin. Mol. Cell. Biol. 20: 2031-2042.

17. Li, J,. Wang, J; Wang, J; Nawaz, Z; Liu, J., Jun, Q., andWong, J. 2000. Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J. 19(16): 4342-4350.

18. Wang, H., Huang, Z., Xia, L., Feng, Q., Erdjument-Bromage, H., Strahl, BD., Briggs, SD., Allis, CD.,Wong, J., Tempst, p and Zhang, Y. 2001. Methylation of Histone H4 at Arginine 3 Facilitates Transcriptional Activation by Nuclear Hormone Receptor. Science 293: 853-857.

19. Liu, Z.,Wong, J., Tsai, S.Y., Tsai, M-J and O’Malley B.W. 2001. Sequential recruitment of steroid receptor coactivator-1 (SRC-1) and p300 enhances progesterone receptor-dependent initiation and reinitiation of transcription from chromatin. PNAS 98: 12426-12431.

20. Huang, Z., Li, J. andWong, J. 2002. Androgen receptor possesses an intrinsic-hormone-independent trans-activation activity. Molecular Endocrinology. 16: 924-937.

21. Liu Z, Auboeuf D,Wong J, Chen JD, Tsai SY, Tsai MJ, O''Malley BW. 2002. Coactivator/corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486. Proc Natl Acad Sci U S A. 99(12):7940-4.

22. Li, J; Lin, Q; Wade, P., Wang, W andWong, J. 2002. Specific targeting and constitutive association of histone deacetylase complexes during transcriptional repression. Genes & Development 16: 687-692.

24. Li, J., Lin, Q., Yoon, H-G., Huang, Z., Strahl, B.D., Allis, C.D., andWong, J.2002. The involvement of multiple histone methylation in transcriptional regulation by thyroid hormone receptor. Mol Cell Biol 22 (16): 5688-5697.

25.Wong J. 2002. Transcriptional regulation by thyroid hormone receptor in chromatin. Thyroid hormone receptors: Methods in Molecular Biology edited by Aria Baniahmad, p177-194.

26. Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA,Wong J, Schiff R, Allred DC and Clark GM. 2003. Overexpression of the Estrogen Receptor Coactivator AIB1 (SRC3) and the HER-2/neu Oncogene are Both Necessary for the Tamoxifen-Resistance in ER-Positive Primary Breast Cancers. J Natl Cancer Insti. 95(5):353-61.

27. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J andWong J. 2003. Purification and Functional Characterization of the Human N-CoR Complex: the Roles of HDAC3 and two WD-40 Repeat Subunits TBL1 and TBLR1. EMBO J 22(6):1336-1346.

28. Huang ZQ, Li J, Sachs LM, Cole PA andWong J. 2003. A Role for Cofactor-Cofactor and Cofactor-Histone Interaction in Targeting of CBP/p300, SWI/SNF and Mediator for transcription. EMBO J 22(9):2146-2155.

29. Yoon HG, Chan DW, Reynolds AB, Qin J andWongJ. 2003. Kaiso targets the N-CoR corepressor complex for DNA methylation mediated repression. Molecular Cell 12, 723-734.

30. Paul R. Thompson, Dongxia Wang, Ling Wang, Marcella Fulco, Natalia Pediconi, DianZheng Zhang, Woojin An, Qingyuan Ge, Robert G. Roeder,Wong J, Massimo Levrero, Vittorio Sartorelli, Robert J. Cotter, Philip A. Cole. 2004. Regulation of the p300 HAT Domain via a Novel Activation Loop. Nature Structural and Molecular Biology. 11(4): 308-15.

31. Wu RC, Qin J, Yi P,Wong J,Tsai SY, Tsai MJ, O''Malley BW. 2004. Selective Phosphorylations of the SRC-3/AIB1 Coactivator Integrate Genomic Reponses to Multiple Cellular Signaling Pathways. Molecular Cell.15(6):937-49.

32. Yoon HG, Choi Y, Cole PA andWong J. 2005 Reading and Function of a histone code involved in targeting corepressor complexes for repression. Mol Cell Biol;25(1):324-335.

33. Stewart MD, Li J andWong J. 2005 Relationship between H3 lysine 9 methylation, transcription repression and heterochromatin protein 1 recruitment. Mol Cell Biol;25(7):2525-38.

34. Zhang D, Yoon HG andWong J. 2005. JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol;25(15):6404-14.

35. Burd CJ, Petre CE, Morey LM, Wang Y, Revelo MP, Haiman CA, Lu S, Fenoglio-Preiser CM, Li J, Knudsen ES,Wong Jand Knudsen KE. 2006 Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation. Proc Natl Acad Sci U S A; 103:2190-5.

36. Yoon, H. G., andWong J. 2006. The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor. Mol Endocrinol 20:1048-60.

37. Stewart D, Tomita A, Shi YB,Wong J. 2006. Chromatin immunoprecipitation for studying transcriptional regulation in Xenopus oocytes and tadpoles. Methods Mol Biol. 322:165-81.

38. Klose, R. Yamane JK, Bae Y, Zhang D, Erdjument-Bromage H, Tempst P,Wong Jand Zhang Y. 2006. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442:312-316.

39. Li, J., Fu J, Toumazou C, Yoon HG, andWong J. 2006. A role of the amino-terminal (N) and carboxyl-terminal (C) interaction in binding of androgen receptor to chromatin. Mol Endocrinol 20:776-85.

40. Yamane, K., Toumazou C, Tsukada YI, Erdjument-Bromage H, Tempst P,Wong Jand Zhang Y. 2006. JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor. Cell 125:483-95.

41. Stewart, M. D., J. Sommerville, andJ. Wong. 2006. Dynamic regulation of histone modifications in Xenopus oocytes through histone exchange. Mol Cell Biol 26:6890-901.

42. Fu, J., Yoon, HG., Qin, J. andWong J. 2007. Regulation of P-TEFb Elongation Complex Activity by CDK9 Acetylation. Mol Cell Biol. 27(13):4641-51.

榮譽

1997 National Research Service Award.

1996 Excellent Poster Award in Gordon Research Conference on "Hormone Action"

1997 The 1997 NIH Excellent Research Award.

1997 Excellent Poster Award in Gordon Research Conference on "Hormone Action"

2001 The 2001 Richard E. Weitzman Memorial Award from Endocrine Society

2004 2004 MCB Research Excellence Award.