成员介绍

张晓坤

教授
     博士生导师
     电话:0592-2181851
     Email:xkzhang@xmu.edu.cn     

个人简历

张晓坤博士、教授,博士生导师,厦门大学药学院院长,教育部长江学者讲座教授,福建省引进高层次创业创新人才,兼任美国加利福尼亚州Sanford-Burnham医学研究所教授。

教育背景:

张晓坤教授1982年毕业于厦门大学生物学系,1989年获美国佛蒙特州大学生物化学博士学位, 自1989年起在美国Sanford-Burnham医学研究所从事核激素受体的基础研究和药物开发应用工作, 1989-1992年美国加利福尼亚州Sanford-Burnham医学研究所开展博士后的工作,1993年开始在美国加利福尼亚州拉霍亚Sanford-Burnham医学研究所组建自己的实验室,任助理教授,2006年升任教授。

研究方向

张晓坤教授长期从事核激素受体的前沿研究,主要集中于维生素A、视黄醇类化合物和衍生物的抗癌作用,以及凋亡信号转导通路的研究。在《自然》、《科学》及《细胞》等国际核心期刊发表了100余篇具有重要创见的核激素受体研究论文,并在美国获得十几项专利。张晓坤教授是核激素受体RXR同源二聚体及异源二聚体作用机制的发现者,根据其发现的新型分子作用机制,张晓坤教授及其团队在1999年成功开发了世界上第一个针对核受体RXR靶点的抗癌专利药Targretin。Targretin被《自然药物开发》及药物界同行认为是从1993~2001年9年间国际上22个被美国FDA批准的最有创新突破的靶点药物之一。近年来张晓坤教授及团队率先在国际上报道了核激素受体的非基因型作用机制及针对该机制的靶点药物开发新模式,并发现了多个针对该模式的具有开发潜力的药物先导小分子化合物及小肽,为寻找高效低毒的靶向核激素受体的药物及制定个性化治疗策略探索了一条新的途径。

根据张晓坤博士参予的发 明专利由美国Ligand 制药公司开发的抗癌新药Targretin /Bexarotene 已由FDA批准广泛应用于癌症病人的治疗。

近期主要代表论著:

代表文章

  1. Zhang, X-k, Hoffmann, B., Tran, P., Graupner, G., and Pfahl, M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature (London) 355: 441-446. 1992.

  2. Zhang, X-k, Lehmann, J.M., Hoffmann, B., Dawson, M., Cameron, J., Graupner, G., Hermann, T., Tran, P., and Pfahl, M. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature (London) 358: 587-591. 1992.

  3. Liu, Y., Lee, M-O., Wang, H-G., Li, Y., Hashimoto, Y., Klaus, M., Reed, J., andZhang, X-kRAR mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol. Cell. Biol. 16: 1138-1149. 1996.

  4. Wu, Q., Li, Y., Liu, R., Agadir, A., Lee, M-O., Liu, Y., andZhang, X-kModulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors Nur77 and COUP-TF and their heterodimerization. EMBO J. 16: 1656-1669. 1997.

  5. Li, Y., Lin, B., Agadir, A., Liu, R., Dawson, M.I., Reed, J.C., Fontana, J.A., Bost, F., Hobbs, P.D., Zheng, Y., Chen, G.Q., Shroot, B., Mercola, D., andZhang, X-kMolecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. Mol. Cell. Biol. 18: 4719-4731. 1998.

  6. Li, H., Kolluri, S., Gu, J., Dawson, M.I., Cao, X., Hobbs, P., Lin, B., Chen, G-q., Lu, J-s., Lin, F., Xie, Z., Fontana, J. A., Reed, J. C., andZhang, X-kCytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science. 289: 1159-1164. 2000.

  7. Lin, B., Kolluri, S., Lin, F., Liu, W., Han, Y-h., Cao, X., Dawson, M.I., Reed, J.C., andZhang, X-kConversion of Bcl-2 from Protector to Killer by Interaction with Nuclear Orphan Receptor Nur77/TR3. Cell. 116: 527-540. 2004.

  8. Kolluri, S.K., Corr, M., James, S.Y., Bernasconi, M., Lu, D., Liu, W., Cottam, H.B., Leoni, L.M., Carson, D.A., andZhang, X-kThe R-enantiomer of the Non-steroidal Anti-inflammatory Drug Etodolac Binds Retinoid X Receptor and Induces Tumor-selective Apoptosis. Proc. Natl. Acad. Sci. 102: 2525-2530. 2005.

  9. Kolluri, S., Zhu, X., Zhou, X., Lin, B., Chen, Y., Sun, K., Tian, X., Town, J., Cao, X., Lin, F., Zhai, D., Kitada, S., Luciano, F., O’Donnell, E., Cao, Y., He, F., Lin, J., Reed, J.C., Satterthwait, A.C., andZhang, X-kA Short Nur77-Derived Peptide Converts Bcl-2 from a Protector to a Killer. Cancer Cell. 14: 285-298. 2008.

  10. Zhou, H., Liu, W., Su, Y., Wei, Z., Liu, J., Kolluri, S.K., Wu, H., Cao, Y., Chen, J., Wu, Y., Yan, T., Cao, X., Gao, W., Molotkov, A., Jiang, F., Li, W-G., Lin, B., Zhang, H-P., Yu, J., Luo, S-P., Zeng, J-Z., Duester, G., Huang, P-Q., andZhang, X-kNSAID Sulindac and Its Analogs Bind RXR and Inhibit RXR-dependent AKT Signaling. Cancer Cell. 17: 560-573. 2010.

Publications

  1. Zhang, X-k, Huang, D.P., Chiu, D.K., and Chiu, J.F. The expression of oncogenes in human developing liver and hepatomas. Biochem. Biophys. Res. Comm. 142: 932-938. 1987.

  2. Zhang, X-k, Wang, Z., Lee, A., Huang, D.P., and Chiu, J.F. Differential expression of cellular oncogenes during rat liver development. Cancer Lett. 41: 147-155. 1988.

  3. Li, P.M., Zhong, J.L., Chen, R.Q.,Zhang, X-k, Ho, K.L., Chiu, J.F., and Huang, D.P. Zhi-mu saponin inhibits alpha-fetoprotein gene expression in developing rat liver. Int. J. Biochem. 21: 15-22. 1989.

  4. Graupner, G., Wills, K.N., Tzukerman, M.,Zhang, X-k, and Pfahl, M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic acid receptor activity. Nature (London) 340: 653-656. 1989.

  5. Zhang, X-k, Huang, D.P., Qiu, D.K., and Chiu, J.F. The expression of c-myc and c-N-ras in human cirrhotic livers, hepatocellular carcinomas and liver tissue surrounding the tumors. Oncogene 5: 909-914. 1990.

  6. Hoffmann, B., Lehmann, J.M.,Zhang, X-k, Hermann, T., Graupner, G., and Pfahl, M. A retinoic acid receptor-specific element controls the retinoic acid receptor- promoter. Mol. Endocrinol. 4: 1727-1736. 1990.

  7. Tzukerman, M.,Zhang, X-k, Hermann, T., Wills, K.N., Graupner, G., and Pfahl, M. The human estrogen receptor has transcriptional activator and repressor functions in the absence of ligand. New Biol. 2: 613-620. 1990.

  8. Pfahl, M., Tzukerman, M.,Zhang, X-k, Lehmann, J.M., Hermann, T., Wills, K.N., and Graupner, G. Nuclear retinoic acid receptors: cloning, analysis, and function. Methods Enzymol. 189: 256-270. 1990.

  9. Zhang, X-k, Zucker, M.I., Huang, D.P., Lin, T-S., Prusoff, W.H., and Chiu, J.F. Alteration of cellular oncogene expression in L1210 cells by a nitrosourea alalog of thymidine. Cancer Comm. 3: 119-126. 1991.

  10. Zhang, X-k, Dong, J.M., and Chiu, J.F. Regulation of -fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site. J. Biol. Chem. 266: 8248-8254. 1991.

  11. Graupner, G.,Zhang, X-k, Tzukerman, M., Wills, K.N., Hermann, T., and Pfahl, M. Thyroid hormone receptors repress estrogen receptor activation of a TRE. Mol. Endocrinol. 5: 365-372. 1991.

  12. Hermann, T.,Zhang, X-k, Tzukerman, M., Wills, K.N., Graupner, G., and Pfahl, M. Regulatory functions of a non-ligand-binding thyroid hormone receptor isoform. Cell Regul. 2: 565-574. 1991.

  13. Pfahl, M.,Zhang, X-k, Lehmann, J.M., Husmann, M., Graupner, G., and Hoffmann, B. Molecular mechanisms of retinoic acid action. In G. Morriss-Kay (ed.), Retinoids in normal development and teratogenesis. Oxford University Press, Oxford. p. 51-64. 1992.

  14. Zhang, X-k, Wills, K.N., Graupner, G., Tzukerman, M., Hermann, T., and Pfahl, M. Ligand-binding domain of thyroid hormone receptors modulates DNA binding and determines their bifunctional roles. New Biol. 3: 169-181. 1991.

  15. Wills, K.N.,Zhang, X-k, and Pfahl, M. Coordinate expression of functionally distinct thyroid hormone receptor  isoforms during neonatal brain development. Mol. Endocrinol. 5: 1109-1119. 1991.

  16. Tzukerman, M.,Zhang, X-k, and Pfahl, M. Inhibition of estrogen receptor activity by the tumor promoter 12-O-tetradeconylphorbol-13-acetate: a molecular analysis. Mol. Endocrinol. 5: 1983-1992. 1991.

  17. Yang-Yen, H-F*.,Zhang, X-k*, Graupner, G., Tzukerman, M., Sakamoto, B., Karin, M, and Pfahl, M. Antagonism between retinoic acid receptors and AP-1: implications for tumor promotion and inflammation. New. Biol. 3: 1206-1219. 1991. *Equal contribution.

  18. Zhang, X-k, Tran, P.B., and Pfahl, M. DNA binding and dimerization determinants for thyroid hormone receptor  and its interaction with a nuclear protein. Mol. Endocrinol. 5: 1909-1920. 1991.

  19. Zhang, X-k, Wills, K.N., Husmann, M., Hermann, T., and Pfahl, M. Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. Mol. Cell. Biol. 11: 6016-6025. 1991.

  20. Zhang, X-k, Hoffmann, B., Tran, P., Graupner, G., and Pfahl, M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature (London) 355: 441-446. 1992.

  21. Lehmann, J.M.,Zhang, X-k, and Pfahl, M. RAR2 expression is regulated through a retinoic acid response element embedded in SP1 sites. Mol. Cell. Biol. 12: 2976-2985. 1992.

  22. Hermann, T., Hoffmann, B.,Zhang, X-k, Tran, P., and Pfahl, M. Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities. Mol. Endocrinol. 6: 1153-1162. 1992.

  23. Zhang, X-k, Egan, J.O., Huang, D-p., Sun, Z.L., Chien, V.K., and Chiu, J.F. Hepatitis B virus DNA integration and expression of an erbB-like gene in human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 188: 344-351. 1992.

  24. Tran, P.,Zhang, X-k, Salbert, G., Hermann, T., Lehmann, J.M., and Pfahl, M. COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol. Cell. Biol. 12: 4666-4676. 1992.

  25. Zhang, X-k, Lehmann, J.M., Hoffmann, B., Dawson, M., Cameron, J., Graupner, G., Hermann, T., Tran, P., and Pfahl, M. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature (London) 358: 587-591. 1992.

  26. Hermann, T., Hoffmann, B., Piedrafita, F.J.,Zhang, X-k, and Pfahl, M. V-erb A requires auxiliary proteins for dominant negative activity. Oncogene. 8: 55-65. 1993.

  27. Zhang, X-kand Pfahl, M. Regulation of retinoid and thyroid hormone action through homodimeric and heterodimeric receptors. Trends Endocrinol. Metab. 4: 156-162. 1993.

  28. Lehmann, J.M.,Zhang, X-k, Graupner, G., Lee, M.O., Hermann, T., Hoffmann, B., and Pfahl, M. Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching. Mol. Cell. Biol. 13: 7698-7707. 1993.

  29. Zhang, X-kand Pfahl, M. Hetero- and homodimeric receptors in thyroid hormone and vitamin A action. Receptor. 3: 183-191. 1993.

  30. Zhang, X-kand Pfahl, M. Molecular mechanisms of action for vitamin-A derived hormones in receptor-mediated biological processes. Implications for Evaluating Carcinogens. (ed. T.J. Slaga). Wiley-Liss Press. 1993.

  31. Zhang, X-k, Salbert, G., Lee, M-O., and Pfahl, M. Mutations that alter ligand-induced switches and dimerization activities in the retinoid X receptor. Mol. Cell. Biol. 14: 4311-4323. 1994.

  32. Pfahl, M., Apfel, R., Bendik, I., Fanjul, A., Graupner, G., Lee, M-O., La-Vista, N., Lu, X-P, Piedrafita, J., Ortiz-Caseda, A., Salbert, G., andZhang, X-kNuclear retinoid receptors and their mechanism of action. Vitamins and hormones. (ed. Gerald Litwac). Vol. 49, pp. 327-382. 1994.

  33. Lee, M-O., Hobbs, P.D.,Zhang, X-k, Dawson, M.I., and Pfahl, M. A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter. Proc. Nat. Acad. Sci. 91: 5632-5636. 1994

  34. Zhang, X-k, Liu, Y., Lee, M-O., and Pfahl, M. A specific defect in the retinoic acid response associated with human lung cancer cell lines. Cancer Res. 54: 5663-5669. 1994.

  35. Zhang, X-kMolecular mechanisms of action for vitamin A-derived hormones. Prog. Clin. Biol. Res. 387: 59-71. 1994.

  36. Lee, M-O., Liu, Y., andZhang, X-kA retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensibility in transcriptional activation of the lactoferrin gene. Mol. Cell. Biol. 15: 4194-4207. 1995.

  37. Alam, M., Zhestkov, V., Sani, B.P., Venepally, P., Levin, A.A., Kazmer, S., Li, E., Norris, A.W.,Zhang, X-k, Lee, M.-O., Hill, D.L., Lin, T.-H., Brouillette, and Muccio, D.D. Conformationally defined 6-s-trans retinoic acid analogs. 2: Selective agonists for nuclear receptor binding and transactivational activity. J. Med. Chem. 38: 2302-2310. 1995.

  38. Dawson, M.I., Chao, W-R., Pine, P., Jong, L., Hobbs, P.D., Rudd, C., Quick, T.C., Niles, R.M.,Zhang, X-k, Lombardo, A., Ely, K.R., Shroot, B., and Fontana, J.A. Correlation of retinoid binding affinity to RAR with retinoid inhibition of growth of estrogen receptor-positive MCF-7 mammary carcinoma cells. Cancer Res. 55: 4446-4451. 1995.

  39. Zhang, X-k, Liu, Y., and Lee, M-O. Retinoid receptors in human lung cancer and breast cancer. Mutat. Res. 350: 267-277. 1996.

  40. Liu, Y., Lee, M-O., Wang, H-G., Li, Y., Hashimoto, Y., Klaus, M., Reed, J., andZhang, X-kRAR mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol. Cell. Biol. 16: 1138-1149. 1996.

  41. Sani, P.,Zhang, X.-k., Hill, D.L., and Shealy, Y.F. Retinyl methyl ether: binding to transport proteins and effect on transcriptional regulation. Biochem. Biophys. Res. Comm. 223: 293-298. 1996.

  42. Sani, B.P., Venepally, P.,Zhang, X-k, Hill, D.L., and Shealy, F. Biochemical characteristics and differentiating activity of 4-oxo analogs of retinoic acid. Anticancer Res. 16: 1177-1181. 1996.

  43. Wu, Q., Li, Y., Liu, R., Agadir, A., Lee, M-O., Liu, Y., andZhang, X-kModulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization. EMBO J. 16: 1656-1669. 1997.

  44. Agadir, A., Shealy, Y. F., Hills, D.L., andZhang, X-kRetinyl methyl ether down-regulates activator protein 1 transcriptional activation in breast cancer cells. Cancer Res. 57: 3444-3450. 1997.

  45. Wu, Q., Dawson, M.I., Zheng, Y., Hobbs, P.D., Agadir, A., Jong, L., Li, Y., Liu, R., Lin, B., andZhang, X-kInhibition of trans-RA-resistant human breast cancer cell growth by retinoid X-receptor-selective retinoids. Mol. Cell. Biol. 17: 6598-6608. 1997.

  46. Chao, W-r, Hobbs, P.D., Jong, L.,Zhang, X-k, Zheng, Y., Wu, Q., Shroot, B., and Dawson, M.I. Effects of receptor class- and subtype-selective retinoids and an apoptosis-inducing retinoid on the adherent growth of the NIH:OVCAR-3 ovarian cancer cell line in culture. Cancer Lett. 115: 1-7. 1997.

  47. Giannini, G., Dawson, M.I.,Zhang, X-k, and Thiele, C.J. Activation of three distinct RXR/RAR heterodimers induces growth arrest and differentiation of neuroblastoma cells. J. Biol. Chem. 272: 26693-26701. 1997.

  48. Li, Y., Dawson, M.I., Agadir, A., Lee, M-O., Jong, L., Hobbs, P.D., andZhang, X-kRegulation of RAR beta expression by RAR- and RXR-selective retinoids in human lung cancer cell lines: effect on growth inhibition and apoptosis induction. Int. J. Cancer 75: 88-95. 1998.

  49. Muccio, D.D., Brouillette, W.J., Breitman, T.R., Taimi, M., Emanuel, P.D.,Zhang, X-k, Chen, G-q., Sani, B.P., Venepally, P., Lakshimi, R., Alam, M., Simpson-Herren, L., and Hill, D.L. Conformationally defined retinoic acid analogues. 4, potential new agents for acute promyelocytic and juvenile myelomonocytic leukemias. J. Med. Chem. 41: 1679-1687. 1998.

  50. Liu, R., Takayama, S., Zheng, Y., Froesch, B., Chen, G-q., Zhang, X., Reed, J.C., andZhang, X-kInteraction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells. J. Biol. Chem. 273: 16985-16992. 1998.

  51. Li, Y., Lin, B., Agadir, A., Liu, R., Dawson, M.I., Reed, J.C., Fontana, J.A., Bost, F., Hobbs, P.D., Zheng, Y., Chen, G.Q., Shroot, B., Mercola, D., andZhang, X-kMolecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. Mol. Cell. Biol. 18: 4719-4731. 1998.

  52. Dawson, M.I., Chao, W.R., Hobbs, P.D., andZhang, X-kEffects of trans-retinoic acid, 9-cis-retinoic acid, 1alpha, 25-(dihydroxy) vitamin D3 and a novel apoptosis-inducing retinoid on breast cancer and endothelial cell growth. Cancer Lett. 133: 1-8. 1998.

  53. Agadir, A., Lazzaro, G., Zheng, Y.,Zhang, X-k, and Mehta, R.G. Resistance of HBL100 human breast epithelial cells to vitamin D action. Carcinogenesis 20: 577-582. 1999.

  54. Li, Y., Hashimoto, Y., Agadir, A., Kagechika, H., andZhang, X-kIdentification of a novel class of retinoic acid receptor -selective retinoid antagonists and their inhibitory effects on AP-1 activity and retinoic acid-induced apoptosis in human breast cancer cells. J. Biol. Chem. 274: 15360-15366. 1999.

  55. Agadir, A., Chen, G-q., Bost, F., Li, Y., Mercola, D., andZhang, X-kDifferential effect of retinoic acid on growth regulation by phorbol ester in human cancer cell lines. J. Biol. Chem. 274: 29779-29785. 1999.

  56. Lin, B., Chen, G-q., Xiao, D., Kolluri, S.K., Cao, X., Su, H., andZhang, X-kOrphan receptor COUP-TF is required for induction of retinoic acid receptor , growth inhibition and apoptosis by retinoic acid in cancer cells. Mol. Cell. Biol. 20: 957-970. 2000.

  57. Dawson, M.I., Hobbs, P.D., Jong, L., Xiao, D., Chao, W-r., Pan, C., andZhang, X-ksp2-bridged diaryl retinoids: effect of bridge-region substitution on retinoid X receptor (RXR) selectivity. Bioorg. Med. Chem. Lett. 10: 1307-1310. 2000.

  58. Dawson, M.I., Jong, L., Hobbs, P.D., Xiao, D., Feng, K.C., Chao, W-r., Pan, C., Fontana, J.A., andZhang, X-k4-[3-(5,6,7,8-Tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl)-phenyl]benzoic acid and hetercyclic-bridged analogs are novel retinoic acid receptor subtype and retinoid X receptor alpha agonists. Bioorg. Med. Chem Lett. 10: 1311-1313. 2000.

  59. Lin, F., Xiao, D., Kolluri, S.K., andZhang, X-kUnique anti-activator protein-1 activity of retinoic acid receptor-. Cancer Res. 60: 3271-3280. 2000.

  60. Dawson, M.I.,Zhang, X-k, Hobbs, P.D., and Jong, L. Synthetic retinoids and their usefulness in biology and medicine. Vitamin A and retinoids: an update of biological aspects and clinical applications. M.A. Livrea (ed.), Birkhäuser Verlag Basel/Switzerland. pp161-196. 2000.

  61. Li, H., Kolluri, S., Gu, J., Dawson, M.I., Cao, X., Hobbs, P., Lin, B., Chen, G-q., Lu, J-s., Lin, F., Xie, Z., Fontana, J. A., Reed, J. C., andZhang, X-kCytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science. 289: 1159-1164. 2000.

  62. Dawson, M.I., Park, J., Chen, G-q., Chao, W-r., Dousman, L., Waleh, N., Hobbs, P., Jong, L., Toll, L.,Zhang, X-k, Gu, J., Agadir, A., Merchant, J., Bai, L., Verma, A., Thacher, S., Chandraratna, R., Shroot, B., and Hill, D. Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-Tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by retonoids. A potential role for Trans-RA-induced ZBP-89 in ODC inhibition. Int. J. Cancer. 91: 8-21. 2001.

  63. Dawson, M.I., Hobbs, P., Peterson, V., Leid, M., Lange, C., Feng, K., Chen, G., Gu, J., Li, H., Kolluri, S.,Zhang, X-k, Zhang, Y., and Fontana, J. Apoptosis induction in cancer cells by a novel analogue of 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid lacking retinoid receptor transcriptional activation activity. Cancer Research. 61: 4723-4730. 2001.

  64. Stelle-Perkins, G., Fang, W., Yang, X-H., Van Gele, M., Carling, T., Gu, J., Buyse, I.M., Fletcher, J.A., Liu, J., Bronson, R., Chadwick, R.B., de la Chapelle, A.,Zhang, X-k, Speleman, F., and Huang, S. Tumor formation and inactivation of RIZ1, an R-binding member of a nuclear protein-methyltransferase superfamily. Genes Dev. 15: 2250-2262. 2001.

  65. Chen, G-q., Lin, B., Dawson, M.I., andZhang, X-kNicotine modulates the effects of retinoids on growth inhibition and RAR expression in lung cancer cells. Int. J. Cancer. 99: 171-178. 2002.

  66. Zhang, Y., Dawson, M.I., Mohammad, R., Rishi, A.K., Farhana, L., Feng, K-C., Leid, M., Perterson, V.,Zhang, X-k, Edelstein, M., Eilander, D., Biggar, S., Wall, N., Reichert, U., and Fontana, J.A. Induction of apoptosis of human B-CLL and ALL cells by a novel retinoid and its non-retinoidal analog. Blood. 100: 2917-2925. 2002.

  67. Lin, F., Kolluri, S., Chen, G-q., andZhang, X-kRegulation of Retinoic Acid-induced Inhibition of AP-1 Activity by Orphan Receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor. J. Biol. Chem. 277: 21414-21422. 2002.

  68. Peterson, V.J., Barofsky, E., Deinzer, M.L., Dawson, M.I., Feng, K.C.,Zhang, X-k, Madduru, M.R., and Leid, M. Mass-spectrometric analysis of agonist-induced retinoic acid receptor gamma conformational change. Biochemical Jour. 362: 173-181. 2002.

  69. Zhang, X-kVitamin A and apoptosis in prostate cancer. Endocrine-Related Cancer. 9: 87-102. 2002.

  70. Li, M., Song, S., Lippman, S.M.,Zhang, X-k, Liu, X., Lotan, R., and Xu, X-c. Induction of Retinoic Acid Receptor- and Sensitivity to Retinoic Acid of Esophageal Cancer Cells Dependent on Cyclooxygenase-2 Expression. Oncogene. 21: 411-418. 2002.

  71. Dawson M.I. andZhang, X-kDiscovery and design of retinoic acid receptor and retinoid X receptor class- and subtype-selective synthetic analogs of all-trans-retinoic acid and 9-cis-retinoic acid. Curr. Med. Chem. 9: 623-637. 2002.

  72. Zhang, Y., Dawson, M.I., Ning, Y., Polin, L., Parchment, R.E., Corbett, T., Mohammad, A.N., Feng, K-C., Farhana, L., Rishi, A.K., Hogge, D., Leid, M., Peterson, V.J.,Zhang, X-k, Mohammad, R., Lu, J-S., Willman, C., VanBuren, E., Biggar, S., Edelstein, M., Eilender, D., and Fontana, J.A. Induction of apoptosis in retinoid-refractory acute myelogenous leukemia by a novel AHPN analog. Blood. 102: 3743-3752. 2003.

  73. Kolluri, S., Bruey-Sedano, N., Cao, X., Lin, B., Lin, F., Han, Y-h., Dawson, M.I., andZhang, X-kMitogenic Effect of Orphan Receptor TR3 and its Regulation by MEKK1 in Lung Cancer Cells. Mol. Cell. Biol. 23: 8651-8667. 2003.

  74. James, S., Lin, F., Kolluri, S., Dawson, M.I., andZhang, X-kRegulation of retinoic acid receptor  expression by peroxisome proliferator-activated receptor  ligands in cancer cells. Cancer Res. 63: 3531-3538. 2003.

  75. Liu, Y., Ren, H., Wu, C., Bai, S.,Zhang, X-k, and Ru., B. Lin, B. Attenuation of zinc-induced neuronal death by the interaction of growth inhibitory factor with Rab3A in rat hippocampal neurons. Neurosci Lett. 358: 149-152, 2004.

  76. Lin, B., Kolluri, S., Lin, F., Liu, W., Han, Y-h., Cao, X., Dawson, M.I., Reed, J.C., andZhang, X-kConversion of Bcl-2 from Protector to Killer by Interaction with Nuclear Orphan Receptor Nur77/TR3. Cell. 116: 527-540. 2004.

  77. Castro-Obregón, S., Rao, R., del Rio, G., Chen, S., Poksay, K., Rabizadeh, S., Vesce, S.,Zhang, X-k, Swanson, R., and Bredesen, D. Alternative, non-apoptotic programmed cell death: mediation by Arrestin 2, ERK2 and Nur77. J Biol Chem. 279: 17543-17553. 2004.

  78. Dawson, M.I., Harris, D., Liu, G., Hobbs, P., Lange, C., Jong, L., Bruey-Sedano, N., James, S.,Zhang, X-k, Peterson, V., Leid, M., Farhana, L., Rishi, A., and Fontana, J. Antagonist Analogue of 6-[3’-(1-Adamantyl)-4’�hydroxyphenyl]-2-naphthalenecarboxylic Acid (AHPN) Family of Apoptosis Inducers That Effectively Blocks AHPN-Induced Apoptosis but Not Cell-Cycle Arrest. J. Med. Chem. 47: 3518-3536. 2004.

  79. Cavasotto, C.N., Liu, G., James, S.Y., Hobbs, P.D., Peterson, V.J., Bhattacharya, A.A., Kolluri, S.K.,Zhang, X-k, Leid, M., Abagyan, R., Liddington, R.C., and Dawson,.M.I. Determinants of Retinoid X Receptor Transcriptional Antagonism. J. Med. Chem. 47: 4360-4372. 2004.

  80. Carling, T., Kim, K.C., Yang, X.H., Gu, J.,Zhang, X-k, and Huang, S. A histone methyltransferase is required for maximal response to female sex hormones. Mol. Cell Biol. 24: 7032-7042. 2004.

  81. Cao, X., Liu, W., Lin, F., Li, H., Kolluri, S.K., Lin, B., Han, Y-h, Dawson, M.I., andZhang, X-kRetinoid X receptor regulates Nur77/TR3-dependent apoptosis by modulating its nuclear export and mitochondrial targeting. Mol. Cell Biol. 24: 9705-9725. 2004.

  82. Lee, K-W., Ma, L., Yan, X., Liu, B.,Zhang, X-k, and Cohen, P. Rapid Apoptosis Induction by IGFBP-3 Involves an Insulin-like Growth Factor-independent Nucleomitochondrial Translocation of RXR/Nur77. J. Bio. Chem. 280: 16942-16948. 2005.

  83. Kolluri, S.K., Corr, M., James, S.Y., Bernasconi, M., Lu, D., Liu, W., Cottam, H.B., Leoni, L.M., Carson, D.A., andZhang, X-kThe R-enantiomer of the Non-steroidal Anti-inflammatory Drug Etodolac Binds Retinoid X Receptor and Induces Tumor-selective Apoptosis. PNAS. 102: 2525-2530. 2005.

  84. Han, Y.H., Cao, X., Lin, B., Lin, F., Kolluri, S.K., Reed, J.C., Dawson, M.I., andZhang, X-kRegulation of nur77 nuclear export by c-Jun N-terminal kinase and Akt. Oncogene. 25:2974-2986. 2005.

  85. Moll, U.M., Marchenko, N., andZhang, X-kP53 and Nur77/TR3-Transcription Factors that Target Mitochondria for Cell Death Induction. Oncogene 25: 4725-4743. 2006.

  86. Stebbins, J., Jung, D., Leone, M,Zhang, X-k, and Pellecchia, M. A Structure Based Approach to RXR Inhibition. JBC 281: 16643-16648. 2006.

  87. Zeng, J., Sun, D-F., Wang, L., Cao, X., Qi, J-b., Yang, T., Hu, C-q., Liu, W., andZhang, X-kHypericum sampsonii Induces Apoptosis and Nuclear Export of Retinoid X Receptor-alpha. Carcinogenesis. 27: 1991-2000. 2006.

  88. Wang, J.G., Barsky, L.W., Davicioni, E., Weinberg, K.I., Triche, T.J.,Zhang, X-k, and Wu, L. Retinoic acid induces leukemia cell G1 arrest and transition into differentiation by inhibiting cyclin-dependent kinase-activating kinase binding and phosphorylation of PML/RARalpha. FASEB J. 20: 2142-2144. 2006.

  89. Zhai, DY., Sergienko, E., Kitada, S., Luciano, F., Satterswait, AC.,Zhang, XK., and Reed, JC. Exploiting the TR3 interaction with Bcl-2 as a novel therapeutic strategy of cancer and leukemia therapy. BLOOD. 108: 80A-80A 256 Part 1 Nov. 16, 2006.

  90. Andreeff, M., Konopleva, M.,Watt, JC., Samudio, IJ., Satterthwait, AC., Kitada, S.,Zhang, XK., and Reed, JC. A novel peptide containing a nine amino acid sequence from Nur77 induces Bcl-2-dependent apoptosis in AML. BLOOD. 108: 736A-736A 2607 Part 1 Nov. 16, 2006.

  91. Hexin Chen, Huiping Zhang, Jishin Lee, Xiaohui Liang, Xinyan Wu, Tao Zhu,Pang-kuo Lo, Xiaokun Zhang and Saraswati Sukumar. HOXA5 Acts Directly Downstream of Retinoic Acid Receptor and Contributes to Retinoic Acid�Induced Apoptosis and Growth Inhibition. Cancer Res. 67: 8007-8013. 2007.

  92. Zhang, X.-k. Targeting Nur77 Translocation. Expert Opinion on Therapeutic Targets. 11: 59-79. 2007.

  93. Dawson, MI., Xia, ZB., Liu, G., Fontana, JA., Farhana, L., Patel, BB., Arumugarajah, S., Bhuiyan, M.,Zhang, XK., Han, YH., Stallcup, WB., Fukushi, JI., Mustelin, T., Tautz, L., Su, Y., Harris, DL., Waleh, N., Hobbs, PD., Jong, L., Chao, WR., Schiff, LJ., Sani, BP. An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor: Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity. J. Med. Chem. 50: 2622-2639. 2007.

  94. Bisson, WH., Cheltsov, AV., Bruey-Sedano, N., Lin, B., Chen, J., Goldberger, N., May, LT., Christopoulos, A., Dalton, JT., Sexton, PM.,Zhang, XK., and Abagyan, R. Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc. Nat. Acad. Sci.. 104: 11927-11932. 2007.

  95. Luciano, F., Krajewska, M., Ortiz-Rubio, P., Krajewski, S., Zhai, D., Faustin, B., Bruey, J.M,. Bailly-Maitre, B., Lichtenstein, A., Kumar Kolluri, S., Satterthwait ,A.C.,Zhang, X-k, Reed, J.C. Nur77 converts phenotype of Bcl-B, an anti-apoptotic protein expressed in plasma cellsand myeloma. BLOOD, 109: 3849-3855. 2007.

  96. Zeng, J-z., andZhang, X-kNongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation. Anti-Inflammatory & Anti-Allergy Agents Medicinal Chem., 6: 315-331. 2007.

  97. Dawson MI, Xia Z, Jiang T, Ye M, Fontana JA, Farhana L, Xue LP, Patel B, Bhuiyan M, Pellicciari R, Macchiarulo A, Nuti R,Zhang X-K,, Han Y-H, Tautz L, Waleh N, Hobbs P D, Jong L, Chao W, Feng G-S, and Su Y. Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: Effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SHP-2 protein-tyrosine phosphatase activity. J. Med. Chem. 51: 5650-5652, 2008.

  98. Chai, D., Wang, B., Shen, L., Pn, J.,Zhang, X-k, and He, B. RXR agonists inhibits high glucose induced oxidative stress by repressing PKC activity in human endothelial cells. Free Radical Biology & Medicine, 44: 1334-1347. 2008.

  99. Liu, J., Zhou, W., Li, S.S., Sun, Z., Lin, B., Lang, Y.Y., He, J-Y., Cao, X., Yan, T., Wang, L., Lu, J., Han, Y-h., Cao, Y.,Zhang, X.-k., and Zeng J-z. Modulation of Orphan Nuclear Receptor Nur77-Mediated Apoptotic Pathway by Acetylshikonin and Analogues. Cancer Res., 68: 8871-8880. 2008.

  100. Kolluri, S., Zhu, X., Zhou, X., Lin, B., Chen, Y., Sun, K., Tian, X., Town, J., Cao, X., Lin, F., Zhai, D., Kitada, S., Luciano, F., O’Donnell, E., Cao, Y., He, F., Lin, J., Reed, J.C., Satterthwait, A.C., andZhang, X-kA Short Nur77-Derived Peptide Converts Bcl-2 from a Protector to a Killer. Cancer Cell. 14: 285-298. 2008.

  101. Han, Y.H., Zhou, H., Kim, J.H., Yan, T.D., Lee, K.H., Wu, H., Lin, F., Lu, N., Liu, J.,Zeng, J.Z., and Zhang, X.k. A unique cytoplasmic localization of RARgamma and its regulations. J. Biol. Chem. 284:18503-18514. 2009.

  102. Dawson, M.I., Ye, M., Cao, X., Farhana, L., Hu, Q.Y., Zhao, Y., Xu, L.P., Kiselyuk, A., Correa, R.G., Yang, L., Hou, T., Reed, J.C., Itkin-Ansari, P., Levine, F., Sanner, M.F., Fontana, J.A.,Zhang, X.K., Derivation of a retinoid X receptor scaffold from peroxisome proliferator-activated receptor gamma ligand 1-Di(1H-indol-3-yl) methyl-4-trifluoromethylbenzene. ChemMedChem. 4:1106-19. 2009.

  103. Lu J, Dawson MI, Hu QY, Xia Z, Dambacher JD, Ye M,Zhang X-K,, and Li E. The effect of antagonists on the conformational exchange of the retinoid X receptor alpha ligand-binding domain. Mag. Reson. Chem. 47:1071-1080, 2009.

  104. You, X., Zhang, Y.W., Chen, Y., Huang, X, Xu, R., Cao, X.H., Chen, J.,Zhang, X.K.,, and Xu, H.X. Retinoid X receptor- mediates (R)-flurbiprofen’s effect on the levels of Alzheimer’s -amyloid4. Journal of Neurochemistry, 111: 142-149. 2009.

  105. Yan, T.D., Wu, H., Zhang, H.P., Lu, N., Ye, P., Yu, F.H., , Zhou, H., Li, W.G., Cao, X., Lin, Y.Y., He, J.Y., Gao, W.W., Zho, Y., Xie, L., Chen, J.B.,Zhang, X.K.,, and Zeng, J.Z. Oncogenic potential of retinoic acid receptor-gamma in hepatocellular carcinoma. Cancer Res. 70: 2285-2295. 2010.

  106. Zhou, H., Liu, W., Su, Y., Wei, Z., Liu, J., Kolluri, S.K., Wu, H., Cao, Y., Chen, J., Wu, Y., Yan, T., Cao, X., Gao, W., Molotkov, A., Jiang, F., Li, W-G., Lin, B., Zhang, H-P., Yu, J., Luo, S-P., Zeng, J-Z., Duester, G., Huang, P-Q., andZhang, X-kNSAID Sulindac and Its Analogs Bind RXR and Inhibit RXR-dependent AKT Signaling. Cancer Cell. 17: 560-573. 2010.

  107. Kim, B.Y., Yang, J.S., Kwak, S.Y.,Zhang, X.K.,, Han, Y.H. NEMO stabilizes c-Myc through direct interaction in the nucleus. FEBS Lett. 584: 4524-4530. 2010.

  108. Wu, H., Lin, Y., Li, W., Sun, Z., Gao, W., Zhang, H., Xie, L., Jiang, F., Qin, B., Yan, T., Chen, L., Zhao, Y., Cao, X., Wu, Y., Lin, B., Zhou, H., Wong, A.,Zhang, X-k, and Zeng, J-Z. Regulation of Nur77 expression by -catenin and its mitogenic effect in colon cancer cells. FASEB J. 25: 192-205. 2011

  109. Cheng, Z. Völkers, M., Din, S, Avitabile, D. Khan, M., Gude, N., Mohsin, S., Bo, T., Truffa, S., Alvarez, R., Mason, M., Fischer, K.M., Konstandin, M.H.,Zhang, X.K.,, Brown, J.H., and Sussman, M.A. Mitochondrial translocation of Nur77 mediates cardiomyocyte apoptosis. Eur Heart J. Eur 32(17):2179-88, 2011.

  110. Dawson, M.I., Lu, J., Li, E., Xia, Z., Ye, M.,Zhang, X.K.,, Hu, Q-Y. Retinoids, Burger’s Medicinal Chemistry, Drug Discovery and Development, Book Chapter, In Press, Corrected Proof. 2010.

  111. Duan YH, Dai Y, Wang GH, Chen HF, Gao H, Chen JB, Yao XS,Zhang XK,. Xanthone and benzophenone glycosides from the stems of Cratoxylum formosum ssp. pruniflorum. Chem Pharm Bull (Tokyo), 59(2):231-4, 2011.

  112. Liu, DP, Luo Q, Wang GH, Xu Y,Zhang XK,, Chen QC, Chen HF. Furocoumarin derivatives from radix Angelicae dahuricae and their effects on RXRα transcriptional regulation. Molecules 16(8):6339-48, 2011.

  113. Lin T, Wang GH, Lin X, Hu ZY, Chen QC, Xu Y,Zhang XK,, Chen HF. Three new oblongolides from Phomopsis sp. XZ-01, an endophytic fungus from Camptotheca acuminate. Molecules 16(4):3351-9, 2011.

  114. Sun, Z, Cao, X, Jiang, M-M, Qiu, Y, Zhou, H, Chen, L, Qin, B, Wu, H, Jiang, F, Chen, J, Liu, J, Dai, Y, Chen, HF, Hu, QY, Wu, Z, Zeng, J-z, Yao, XS, andZhang, XK.Inhibition of -catenin Signaling by Nongenomic Action of Orphan Nuclear Receptor Nur77. Oncogene In press, 2011.

 

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