科学研究：

研究方向：

主要进行心血管药理学、膜通道药理学、药物发现与开发等相关研究。

承担科研项目情况：

先后主持了美国NIH，PKD和AHA及中国国家自然科学基金、985专项基金（归国人员科研启动基金）等多个研究项目。

目前项目：

1. “重大新药创制”科技重大专项基金子课题：银杏内酯B治疗多囊肾病的药效学研究。

2. 国家自然科学基金：尿素通道蛋白在尿浓缩过程中的作用机制。

3. 国家自然科学基金：水通道蛋白在多囊肾病肾囊泡发生和发展过程中的作用。

4. 高等学校博士学科点专项科研基金：天然单体化合物G315治疗多囊肾病的药理学研究。

5. 985专项基金（归国人员科研启动基金）：膜通道药理学。

科研成果：

(1) 首次发现尿素通道蛋白UT-B 可转运水；

(2) 建立了尿素通道蛋白家族第一个基因敲除小鼠模型；

(3) 发现上皮细胞膜表面矩阵排列蛋白为水通道蛋白AQP4，揭开了一个25年的形态学之谜；

(4) 首次克隆了人水通道蛋白4的cDNA和并鉴定了其基因结构和蛋白特性；

(5) 以基因敲入手段模拟出人遗传性肾性尿崩症第一个小鼠模型；

(6) 成功地建立了水通道1，2，3，4，8的基因敲除小鼠模型；

(7) 首次应用表达水通道蛋白AQP1的重组非复制型腺病毒对的尿崩症小鼠模型进行基因治疗；

(8) 获得了水通道蛋白和尿素通道蛋白在尿浓缩机制中作用的系统性生理学数据；

(9) 发现新的 CFTR突变体改正剂小分子化合物；

(10) 证实CFTR在多囊肾发病过程中起重要作用，提示CFTR抑制剂有可能用于治疗多囊肾；

(11) 发现银杏内酯B可抑制多囊肾囊泡的生成和增大，目前正在进行体内药效学评价；

(12) 利用高通量筛选获得小分子尿素通道抑制剂，并已发现该化合物在体内具有利尿作用。

论文专著：

发表英文论文：

1. Lei T., L. Zhou, A.T. Layton, H. Zhou, X. Zhao, L. Bankir, and B. Yang*. (2011) Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism. Am J Physiol Renal Physiol 2011 Aug 17. [Epub ahead of print]

2. Li X., J. Ran, H. Zhou, T. Lei, L. Zhou, J. Han, and B. Yang*. (2011) Mice Lacking Urea Transporter UT-B Display Depression-Like Behavior. J Mol Neurosci. 2011 Jul 13. [Epub ahead of print]

3. Phuan P.W., B. Yang, J. Knapp, A. Wood, G.L. Lukacs, M.J. Kurth, A.S. Verkman. (2011) Cyanoquinolines with Independent Corrector and Potentiator Activities Restore {triangleup}F508-CFTR Chloride Channel Function in Cystic Fibrosis. Mol Pharmacol. 2011 Jul 5. [Epub ahead of print]

4. Liu L., T. Lei, L. Bankir, D. Zhao, X.Gai, X. Zhao, and B. Yang*.（2011）Erythrocyte permeability to urea and water: comparative study in rodents, ruminants, carnivores, humans, and birds. J Comp Physiol B. J Comp Physiol B. 181：65-72.

5. Lin G., L. Zhao, F. Yin, R. Lan, L. Li, X. Zhang, H. Zhang, and B. Yang*. (2011) TCF3 inhibits F9 embryonal carcinoma growth by the down-regulation of Oct4. Oncol Rep 26: 893-899.

6. Gao J., H. Zhou, T. Lei, L. Zhou, W. Li, X. Li, B. Yang*. （2011） Curcumin inhibits renal cyst formation and enlargement in vitro by regulating intracellular signaling pathways. European Journal of Pharmacology 654：92-99.

7. Liang Z., B. Guo, Y. Li , X. Li , X. Li, L. Zhao, L. Gao, X. Zhao, L. Zhang, B. Yang*. （2011）Plasmid-Based Stat3 siRNA delivered by Hydroxyapatite Nanoparticles Suppresses Prostate Tumor Growth in vivo. Asia J Androl 13:481-486.

8. Yu G., B. Yang, A. S. Verkman, M. J. Kurth.（2010）Isoxazolopyrimidines as Novel DF508-CFTR Correctors. SYNLETT 7：1063–1066

9. Mills A.D., C. Yoo, J.D. Butler, B. Yang, A.S. Verkman, ang M.J. Kurth. (2010) Design and synthesis of a hybrid potentiator-corrector agonist of the cystic fibrosis mutant protein DeltaF508-CFTR. Bioorg Med Chem Lett 20:87-91.

10. Meng Y., C. Zhao, X. Zhang, H. Zhao, L. Guo, B. Lü, X. Zhao X, and B. Yang. (2009) Surface electrocardiogram and action potential in mice lacking urea transporter UT-B. Sci China C Life Sci 52:474-478.

11. Yu H., Y. Meng, L. Wang, X. Jin, L. Gao, L. Zhou, K. Ji, Y. Li, L. Zhao, G. Chen, X. Zhao, and B. Yang*. (2009) Differential Protein Expression in Heart in UT-B Null Mice with Cardiac Conduction Defects. Proteomics 9:504-511

12. Yang B., D. Zhao, and A.S. Verkman. (2009) Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. FASEB J. 23:503-512.

13. Yu G.J., C.L.Yoo, B. Yang, M.W. Lodewyk, L. Meng, T.T. El-Idreesy, J.C. Fettinger, D.J. Tantillo, A.S. Verkman, and M.J. Kurth. (2008) Potent s-cis-locked bithiazole correctors of DeltaF508 cystic fibrosis transmembrane conductance regulator cellular processing for cystic fibrosis therapy. J Med Chem 51:6044-6054.

14. Yoo C.L., G.J. Yu, B. Yang, L.I. Robins, A.S. Verkman, and M.J. Kurth. (2008) 4'-Methyl-4,5'-bithiazole-based correctors of defective delta F508-CFTR cellular processing. Bioorg Med Chem Lett 18:2610-2614.

15. Yang B.*, N.D. Sonawane, D. Zhao, S. Somlo, and A.S. Verkman. (2008) Small-molecule CFTR inhibitors slow cyst growth in polycystic kidney disease. J Am Soc Nephrol 19:1300-1310.

16. Yang B., Z. Zador, and A.S. Verkman. (2008) Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 283:15280-15286.

17. Yang B., H. Zhang, and A.S. Verkman. (2008) Lack of aquaporin-4 water transport inhibition by antiepileptics and arylsulfonamides. Bioorg Med Chem 16:7489-7493.

18. Beall M.H., S. Wang, B. Yang, N. Chaudhri, F. Amidi, and M.G. Ross. (2007) Placental and membrane aquaporin water channels: correlation with amniotic fluid volume and composition. Placenta 28:421-428.

19. Zhao D., N.D. Sonawane, M.H. Levin, and B. Yang*.（2007）Comparative transport efficiencies of urea analogues through urea transporter UT-B. Biochim Biophys Acta 1768: 1815-1821.

20. Guo L., D. Zhao, Y. Song, Y. Meng, H. Zhao, X. Zhao, and B. Yang*. （2007）Reduced urea flux across the blood-testis barrier and early maturation in the male reproductive system in UT-B-null mice. Am J Physiol Cell Physiol 293: C305-C312.

21. Jin S., Y. Liu, L. Xu, Y. Jiang, Y. Wang, B. Yang, H. Yang, and T. Ma. (2006) Cloning and characterization of porcine aquaporin 1 water channel expressed extensively in gastrointestinal system. World J Gastroenterol 12:1092-1097.

22. Pan Y.Z., X.Y. Xiao, D. Zhao, L. Zhang, G.Y. Ji, Y. Li, B. Yang, D.C. He, and X.J. Zhao. (2006) Application of surface-enhanced laser desorption/ionization time-of-flight-based serum proteomic array technique for the early diagnosis of prostate cancer. Asian J Androl 8:45-51.

23. Suen Y.F., L. Robins, B. Yang, A.S. Verkman, M.H. Nantz, and M.J. Kurth. (2006) Sulfamoyl-4-oxoquinoline-3-carboxamides: novel potentiators of defective DeltaF508-cystic fibrosis transmembrane conductance regulator chloride channel gating. Bioorg Med Chem Lett 16:537-540.

24. Yang B.*, D. Zhao, L. Qian, and A.S. Verkman. (2006) Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deleltion. Am J Physiol Renal Physiol 291:F465-F472.

25. Zhao D., L. Bankir, L. Qian, D. Yang, and B. Yang*. (2006) Urea and urine concentrating ability in mice lacking AQP1 and AQP3. Am J Physiol Renal Physiol 291:F429-F438.

26. Butler T.L., C.G. Au, B. Yang, J.R. Egan, Y.M. Tan, E.C. Hardeman, K.N. North, A.S. Verkman, and D.S. Winlaw. (2006) Cardiac Aquaporin Expression in Human, Rat and Mouse. Am J Physiol Heart Circ Physiol 291:H705-H713.

27. Yang B.*, D. Zhao, S. Eugene, and A.S. Verkman. (2006) Evidence from knockout mice against physiologically significant aquaporin-8 facilitated ammonia transport. Am J Physiol cell Physiol 291:C417-C423.

28. Li Z., D. Zhao, B. Gong, Y. Xu, H. Sun, B. Yang, and X. Zhao. (2006) Decreased saliva secretion and down-regulation of AQP-5 in submandibular gland in irradiated rats. Radiat Res 165: 678-687.

29. Yang B., D. Zhao, and A.S. Verkman. (2006) Evidence against functionally significant aquaporin expression in mitochondria. J Biol Chem. 281:16202-16206.

30. Levin M.H,, S. Sullivan, D. Nielson, B. Yang, W.E. Finkbeiner, and A.S. Verkman. (2006) Hypertonic saline therapy in cystic fibrosis: Evidence against the proposed mechanism involving aquaporins. J Biol Chem 281:25803-25812.

31. Yang B.*, J.K. Kim, and A.S. Verkman. (2006) Comparative efficacy of HgCl(2) with candidate aquaporin-1 inhibitors DMSO, gold, TEA(+) and acetazolamide. FEBS Lett 580:6679-6684.

32. Meng Y., X. Zhou, Y. Li, D. Zhao, S. Liang, X. Zhao, and B. Yang* . (2005) A novel mutation at the JK locus causing Jk null phenotype in a Chinese family. Sci China C Life Sci 48:636-640.

33. Yang B., Y. Song , D. Zhao, and A.S. Verkman . (2005) Phenotype analysis of aquaporin-8 null mice. Am J Physiol cell Physiol 288:C1161-C1170.

34. Hara-Chikuma M, B. Yang, N.D. Sonawane, S. Sasaki, S. Uchida, and A.S. Verkman. (2005) ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation. J Biol Chem 280:1241-1247.

35. Klein J.D., J.M. Sands, L. Qian, X. Wang, and B. Yang*. (2004) Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. J Am Soc Nephrol 15:1161-1167.

36. Bankir L., K. Chen, and B. Yang*. (2004) Lack of UT-B in vasa recta and red blood cells prevents urea-induced improvement of urinary concentrating ability. Am J Physiol Renal Physiol 286:F144-F151.

37. Oshio K., D.K. Binder, B. Yang, S. Schecter, A.S. Verkman, and G.T. Manley. (2004) Expression of aquaporin water channels in mouse spinal cord. Neuroscience 127:685-693.

38. Yang B., L. Bankir, A. Gillepsie, C. J. Epstein, and A. S. Verkman. (2002) Urea-selective concentrating defect in transgenic mice lacking urea transporter UT-B. J BIol Chem 277:10633-10637.

39. Fang X., B. Yang, M. A. Matthay and A.S. Verkman. (2002) Evidence against aquaporin-1 dependent CO2 permeability in lung and kidney. J Physiol 542:63-69.

40. Yang B., and A. S. Verkman. (2002) Analysis of double knokout mice lacking aquaporin-1 and urea transporter UT-B: Evidence for UT-B facilitated water transport in erythrocytes. J Biol Chem 277:36782-36786.

41. Mann S.E., E. A. Ricke, B. Yang, A. S. Verkman, and R. N. Taylor. (2002) Expression and localization of aquaporin 1 and 3 in human fetal membranes. Am. J Obstet Gynecol 187:902-907.

42. Yang B., T. Ma, and A. S. Verkman. (2001) Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3. J Biol Chem 276:624-628.

43. Yang B., A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman. (2001) Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. J Biol Chem 276:2775-2779.

44. Song Y., S. Jayaraman, B. Yang, M. A. Matthay, and A. S. Verkman. (2001) Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration. J Gen Physiol 117:573-582.

45. Ma T., S. Jayaraman, K. S. Wang, Y. Song, B. Yang, J. Li, J. A. Bastidas, and A. S. Verkman. (2001) Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Am J Physiol Cell Physiol 280:C126-C134.

46. Yang B., J. M. Verbavatz, Y. Song, L. Vetrivel, G. Manley, W. M. Kao, T. Ma, and A. S. Verkman. (2000) Skeletal muscle function and water permeability in aquaporin-4 deficient mice. Am J Physiol Cell Physiol 278:C1108-C1115.

47. Yang B., T. Ma, J. Y. Dong, and A. S. Verkman. (2000) Partial correction of the urinary concentrating defect in aquaporin-1 null mice by adenovirus-mediated gene delivery. Hum Gene Ther 11:567-575.

48. Yang B., N. Fukuda, A. van Hoek, M. A. Matthay, T. Ma, and A. S. Verkman. (2000) Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes. J Biol Chem 275:2686-2692.

49. van Hoek A. N., T. Ma, B. Yang, A. S. Verkman, and D. Brown. (2000) Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney. Am J Physiol Renal Physiol 278:F310-F316.

50. Song Y., B. Yang, M. A. Matthay, T. Ma, and A. S. Verkman. (2000) Role of aquaporin water channels in pleural fluid dynamics. Am J Physiol Cell Physiol 279:C1744-C1750.

51. Moore M., T. Ma, B. Yang, and A. S. Verkman. (2000) Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5. Exp Eye Res 70:557-562.

52. Ma T., Y. Song, B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman. (2000) Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proc Natl Acad Sci U S A 97:4386-4391.

53. Foster W., A. Helm, I. Turnbull, H. Gulati, B. Yang, A. S. Verkman, and W. R. Skach. (2000) Identification of sequence determinants that direct different intracellular folding pathways for aquaporin-1 and aquaporin-4. J Biol Chem 275:34157-34165.

54. Yang B., T. Ma, Z. Xu, and A. S. Verkman. (1999) cDNA and genomic cloning of mouse aquaporin-2: functional analysis of an orthologous mutant causing nephrogenic diabetes insipidus. Genomics 57:79-83.

55. Yang B., H. G. Folkesson, J. Yang, M. A. Matthay, T. Ma, and A. S. Verkman. (1999) Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice. Am J Physiol 276:C76-C81.

56. Tamarappoo B. K., B. Yang, and A. S. Verkman. (1999) Misfolding of mutant aquaporin-2 water channels in nephrogenic diabetes insipidus. J Biol Chem 274:34825-34831.

57. Chou C. L., M. A. Knepper, A. N. Hoek, D. Brown, B. Yang, T. Ma, and A. S. Verkman. (1999) Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice. J Clin Invest 103:491-496.

58. van Hoek A. N., B. Yang, S. Kirmiz, and D. Brown. (1998) Freeze-fracture analysis of plasma membranes of CHO cells stably expressing aquaporins 1-5. J Membr Biol 165:243-254.

59. Yang B., and A. S. Verkman. (1998) Urea transporter UT3 functions as an efficient water channel. Direct evidence for a common water/urea pathway. J Biol Chem 273:9369-9372.

60. Ma T., B. Yang, M. A. Matthay, and A. S. Verkman. (1998) Evidence against a role of mouse, rat, and two cloned human T1alpha isoforms as a water channel or a regulator of aquaporin-type water channels. Am J Respir Cell Mol Biol 19:143-149.

61. Ma T., B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman. (1998) Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 273:4296-4299.

62. Chou C. L., T. Ma, B. Yang, M. A. Knepper, and A. S. Verkman. (1998) Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice. Am J Physiol 274:C549-C554.

63. Yang B., and A. S. Verkman. (1997) Water and glycerol permeabilities of aquaporins 1-5 and MIP determined quantitatively by expression of epitope-tagged constructs in Xenopus oocytes. J Biol Chem 272:16140-16146.

64. Yang B., A. N. van Hoek, and A. S. Verkman. (1997) Very high single channel water permeability of aquaporin-4 in baculovirus-infected insect cells and liposomes reconstituted with purified aquaporin-4. Biochemistry 36:7625-7632.

65. Verkman A. S., and B. Yang. (1997) Aquaporins and ion conductance. Science 275:1491; discussion 1492.

66. Ma T., B. Yang, and A. S. Verkman. (1997) Cloning of a novel water and urea-permeable aquaporin from mouse expressed strongly in colon, placenta, liver, and heart. Biochem Biophys Res Commun 240:324-328.

67. Ma T., B. Yang, F. Umenishi, and A. S. Verkman. (1997) Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase segment at chromosome locus 12q13. Genomics 43:387-389.

68. Ma T., B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman. (1997) Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4. J Clin Invest 100:957-962.

69. Yang B., D. Brown, and A. S. Verkman. (1996) The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells. J Biol Chem 271:4577-4580.

70. Umenishi F., E. P. Carter, B. Yang, B. Oliver, M. A. Matthay, and A. S. Verkman. (1996) Sharp increase in rat lung water channel expression in the perinatal period. Am J Respir Cell Mol Biol 15:673-679.

71. Ma T., B. Yang, and A. S. Verkman. (1996) cDNA cloning of a functional water channel from toad urinary bladder epithelium. Am J Physiol 271:C1699-C1704.

72. Ma T., B. Yang, and A. S. Verkman. (1996) Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel. Genomics 33:382-388.

73. Ma T., B. Yang, W. L. Kuo, and A. S. Verkman. (1996) cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: evidence for a gene cluster of aquaporins at chromosome locus 12q13. Genomics 35:543-550.

74. Yang B., T. Ma, and A. S. Verkman. (1995) cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units. J Biol Chem 270:22907-22913.

75. Yang B., X. Su, Y. Zhu, K. Sun, D. Xu, Z. Lu, and Y. Jin. (1991) Inhibition of methyl methanesulfonate-induced unscheduled DNA synthesis in spermatozoa of mice by Poly I-C. Acta Pharmacologica Sinica 12(6):497-499.

Review Articles

76. Sun Y., H. Zhou, and B. Yang* (2011) Drug discovery for polycystic kidney disease (invited review). Acta Pharmacologica Sinica 32:805-811.

77. Zhang L., B. Yang, H. Zhang, J. Wang, H. Wang, and X. Zhao (2011) Prostate cancer: an emerging threat to the health of aging men in Asia (invited review). Asian Journal of Andrology 13: 574-578.

78. Yang B.*, and L. Bankir (2005) Urea and urine concentrating ability: New insights from studies on mice (invited review). Am J Physiol Renal Physiol 288:F881-F896.

79. Verkman A.S., K. Oshio, B. Yang, Y. Song, T. Ma, D.K. Binder, M. Papadopoulos, E.I. Solenov, G.T. Manley. (2003) Role of aquaporin water channels in central nervous system revealed by phenotype of aquaporin null mice. J of Neurochemistry 87: 30-40 Suppl.

80. Verkman A.S., and B. Yang. (2002) Aquaporin gene delivery to kidney. Kidney Int 61 Suppl 1:120-124

81. Verkman A.S., J. Li, D. Zhang, B. Yang, T. Ma, G. T. Manley, and Y. Song . (2001) Phenotype analysis of aquaporin transgenic mice. Bull Mol Med 7-8:3-16.

82. Verkman A.S., J. Li, T. Ma, and B. Yang. (2001) Role of aquaporin water channels in kidney function studied using transgenic mice. Clin Exp Nephrol 5:75-84.

83. Yang B*. (2000) The human aquaporin gene family. Current Genomics 1: 91-102.

84. Verkman A.S., B. Yang, Y. Song, G. T. Manley, and T. Ma. (2000) Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol 85:233S-241S.

Books and Chapters

85. A.S. Verkman, B. Yang, W. R. Skach, Y. Song, G.T. Manley and T. Ma. Genetic and biophysical approaches to study water channel biology. In: Current Topics in Membranes, Volume 51. Academic Press. p. 185-233, 2001

86. A.S. Verkman, B. Yang, L.B. Shi, A.N. van Hoek, J. Farinas, A. Frigeri, M. Gropper, M.A. Matthay, B. Tamarappoo, F. Umenishi, and T. Ma. Water channel structure and function. In: Neurohypophysis. T. Saito, K. Kurokawa and S. Yoshida, eds. Elsevier Science, Amsterdam, p. 455-466, 1996

发表中文论文：

1. 李飞，杨宝学*。天然产物与药物发现评述。国际中医中药杂志。2011，33（7）：612-615。

2. 李欣，周虹，杨宝学*。一氧化氮与抑郁症发生相关性的研究进展。国际神经病学神经外科学杂志。2011，37：352-356。

3. 陈燕，郭宝锋，邵晨，杨宝学，赵雪俭。多囊肾小鼠肾功能的改变。中国实验诊断学 2011-01-25。

4. 周澧，周虹，杨宝学*。常染色体显性遗传多囊肾病发病相关信号转导通路的研究进展。中国病理生理杂志。2010 ，26（5）：1020-10-24。

5. 阚秀芳，周虹，杨宝学*。水通道蛋白在多囊肾病小鼠肾囊泡上皮细胞的表达与调控。中华肾脏病杂志。2010，26（1）：39-42。

6. 高晋生，杨宝学*。常染色体显性遗传多囊肾病的治疗研究进展。中国药理学通报 2009，25：141-144。

7. 赵丹，朱建国，王伟华，杨宝学，赵雪俭。水通道蛋白3在人前列腺组织中的表达及意义。中国病理生理杂志 2009-10-15