Qingyu Wu M.D., Ph.D.

Staff

  • Department of Molecular Cardiology
  • Lerner Research Institute / NB50
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • wuq@ccf.org
  • (216) 444-4351

Proteolytic enzymes, also called proteases, are key players in a variety of biological processes.  Our research focuses on a subset of cell membrane proteases that are important in cardiovascular biology and disease.  We have discovered a transmembrane serine protease, corin, from the heart.  We have shown that corin activates atrial natriuretic peptide (ANP), a cardiac hormone that regulates blood pressure and cardiac function.  In knockout mice, a lack of corin causes salt sensitive hypertension.  In humans, CORIN gene variants have been associated with hypertension and heart disease.  Most recently, we have discovered a novel local function of corin and ANP in regulating spiral artery remodeling in the pregnant uterus.  We have identified CORIN gene mutations in patients with pregnancy-induced hypertension.  Currently, we use biochemical tools and mouse models to understand the biology of corin and its role in cardiovascular disease.

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  • Shenghan Chen M.D.
  • Research Associate
  • Location:ND5-08A
  • Phone:(216) 445-7806
  • Fax:(216) 444-9263
  • chens@ccf.org
  • Jianhao Peng Ph.D.
  • Postdoctoral Fellow
  • Location:ND5-08
  • Phone:(216) 445-7806
  • pengj2@ccf.org
  • Hao Wang
  • Graduate Student
  • Location:ND5-08A
  • Phone:(216) 445-7806
  • wangh6@ccf.org

 HIGHLIGHTED PUBLICATIONS

  1. Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q: Role of corin in trophoblast invasion and uterine spiral artery remodeling in pregnancy. Nature 2012;484:246-50.
  2. Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, Wu Q: Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks. Hypertension 2012;60:1352-8.
  3. Wang W, Liao X, Fukuda K, Knappe S, Wu F, Dries DL, Qin J, Wu Q: Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity. Circ Res 2008;103:502-8.
  4. Chan J, Knudson O, Wu F, Morser J, Dole WP, Wu Q:  Hypertension in mice lacking the pro-atrial natriuretic peptide convertase, corin. Proc Natl Acad Sci USA 2005;102:785-90.
  5. Yan W, Wu F, Morser J, Wu Q: Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide converting enzyme. Proc Natl Acad Sci USA 2000;97:8525-9.

 ADDITIONAL PUBLICATIONS

  1. Dong N, Zhou T, Zhang Y, Liu M, Li H, Huang X, Liu Z, Wu Y, Fukuda K, Qin J, Wu Q: Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. J Biol Chem 2014;289(25):17909-17916.
  2. Jiang J, Yang J, Feng P, Zuo B, Dong N, Wu Q, He Y: N-glycosylation is required for matriptase-2 autoactivation and ectodomain shedding. J Biol Chem 2014;289(28):19500-19507.
  3. Zhou Y, Wu Q: Corin in natriuretic peptide processing and hypertension. Curr Hypertens Rep 2014;16:415.doi:10.1007/s11906-013-0415-7.
  4. Yang A, Dai J, Xie Z, Colman RW, Wu Q, Birge RB, Wu Y: High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis. J Immunol 2014;192:4398-408.
  5. Jiao Y, Chen W, Liu Q, Hou J, Yang S, Xu Q, Li Z, Chen Y, He W, Wu Q, Liu Y, Qi X: Pulsatilla saponin A, an active molecule from Pulsatilla Chnensis, induces cancer cell death and inhibits tumor growth in mouse xenograft models. J Surg Res 2014;188:387-95.
  6. Sun S, Liu Z, Zhou H, Li G, Liu M, Yao J, Zhou T, An G, Wu Q, Dong N: The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair. Biomaterials 2014;35:3777-85.
  7. Gao L, Liu M, Dong N, Jiang Y, Lin C-Y, Huang M, Wu D, Wu Q: Matriptase is highly up-regulated in chronic lymphocytic leukemia and promotes cancer cell invasion. Leukemia 2013;27:1191-4.
  8. Dong N, Fang C, Jiang Y, Zhou T, Liu M, Zhou J, Shen J, Fukuda K, Qin J, Wu Q: Corin mutation R539C from hypertensive patients impairs zymogen activation and generates inactive alternative ectodomain fragment. J Biol Chem 2013;288:7867-74.
  9. He Y, Zhao Y, Zhu M, Wu Q, Ruan C: Detection of autoantibodies against platelet glycoproteins in patients with immune thrombocytopenic purpura by flow cytometric immunobead array. Clin Chim Acta 2013;415:176-80.
  10. Zhou Y, Wu Q: Role of corin and atrial natriuretic peptide in preeclampsia. Placenta 2013;34:89-94.
  11. Lu Y, Lu J, Liu Q, Niu J, Zhang S, Wu Q, Qi X: A c.464T>A mutation in VHL gene in a Chinese family with VHL syndrome. J Neuro-Oncol 2013;111:313-8.
  12. Fang C, Shen L, Dong L, Liu M, Shi S, Dong N, Wu Q: Reduced urinary corin levels in patients with chronic kidney disease. Clin Sci (Lond) 2013;124:709-17.
  13. Dong N, Fang C, Jiang Y, Zhou T, Liu M, Zhou J, Shen J, Fukuda K, Qin J, Wu Q: Corin mutation R539C from hypertensive patients impairs zymogen activation and generates inactive alternative ectodomain fragment. J Biol Chem 2013;288:7867-74.
  14. Zhang H, Weingart J, Jiang R, Peng J, Wu Q, Sun X-L: Bio-inspired liposomal thrombomodulin conjugate through bio-orthogonal chemistry. Bioconjugate Chemistry 2013;24:550-9.
  15. Lu Q, Dong N, Wang Q, Yi W, Wang Y, Zhang S, Gu H, Zhao X, Tang X, Jin B, Wu Q, Brass LF, Zhu L: Increased levels of plasma soluble Sema4D in patients with heart failure. PloS One 2013;8(5):e64265.
  16. Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q: Role of corin in trophoblast invasion and uterine spiral artery remodeling in pregnancy. Nature 2012;484:246-50.
  17. Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, Wu Q: Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks. Hypertension 2012;60:1352-8.
  18. Dong N, Chen S, Wang W, Zhou Y, Wu Q: Corin in clinical laboratory diagnostics. Clin Chim Acta 2012;413:378-83.
  19. Dong J, Zhao X, Shi S, Ma Z, Liu M, Wu Q, Ruan C, Dong N: Identification and functional analysis of a novel von Willebrand factor mutation in a family with type 2A von Willebrand disease. PloS One2012;7:e33263.
  20. Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q: Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice. Kidney Int 2012;82:26-33.
  21. Shen J, Wu Q: Corin: a serine protease. Kidney Int 2011;79:138-9.
  22. Antalis TM, Bugge T, Wu Q: Membrane-anchored serine proteases in health and disease. Prog Mol Biol Transl Sci 2011;99:1-50.
  23. Chou H, Hsieh C, Yang H, Wang L, Arakawa Y, Brown K, Wu Q, Lin F, Peters M, Fung JJ, Lu L, Qian S: Hepatic stellate cells regulate immune response via induction of myeloid suppressor cells. Hepatology 2011;53:1007-19.
  24. Jiang J, Wu S, Wang W, Chen S, Peng J, Zhang X, Wu Q: Ectodomain shedding and autocleavage of the cardiac membrane protease corin. J Biol Chem 2011;286:10066-72.
  25. Qi X, Jiang J, Zhu M, Wu Q: Human corin isoforms with different cytoplasmic tails that alter cell surface targeting. J Biol Chem 2011;286:20963-9.
  26. Peng J, Jiang J, Wang W, Qi X, Sun XL, Wu Q: Glycosylation and processing of pro-B-type natriuretic peptide in cardiomyocytes. Biochem Biophys Res Commun 2011;411:593-8.
  27. Xu-Cai YO, Shen J, Chen S, Zhou Y, LaRusch GA, Stavrou E, Schmaier A, Wu Q: Factor XII gene mutation in the Hageman family. J Thromb Haemost 2011;9:2329–31.
  28. Dong N, Chen S, Yang J, He L, Liu P, Zheng D, Li L, Zhou Y, Ruan C, Plow E, Wu Q: Plasma soluble corin in patients with heart failure. Circ Heart Fail 2010;3:207-11.
  29. Xu-Cai YO, Wu Q: Molecular forms of natriuretic peptides in heart failure and their implications. Heart 2010;96:419-24.
  30. Jiang J, Pristera N, Wang W, Zhang X, Wu Q: Effect of sialylated O-glycans in pro-brain natriuretic peptide stability. Clin Chem 2010;56:959-66.
  31. Caen J, Wu Q: Hageman factor, platelets and polyphosphates: early history and recent connection. J Thromb Haemost 2010;8:1670-4.
  32. Polzin P, Kaminski H, Kastner C, Wang W, Kramer S, Gambaryan S, Russwurm M, Peters H, Wu Q, Vandwalle A, Bachmann S, Theilig F: Decreased renal corin expression contributes to sodium retention in proteinuric kidney diseases. Kidney Int 2010;78:660-7.
  33. Dong N, Dong J, Liu P, Xu L, Shi S, Wu Q: Effects of anticoagulants on human plasma soluble corin levels measured by ELISA. Clin Chim Acta 2010;411:1998-2003.
  34. Chen S, Sen S, Young D, Wang W, Moravec CS, Wu Q: Protease corin expression and activity in failing hearts. Am J Physiol Heart Circ Physiol 2010;299:H1687–92.
  35. Wu Q, Xu-Cai YO, Chen S, Wang W:Corin: New insights into the natriuretic peptide system. Kidney Int 2009;75:142-6.
  36. Zhou Y, Jiang J, Cui Y, Wu Q: Corin, atrial natriuretic peptide and hypertension. Nephrol Dial Transplant 2009;24:1071-3.
  37. Braz JC, Gill RM, Corbly AK, Jones BD, Jin N, Vlahos CJ, Wu Q, Shen W: Selective activation of PI3Ka/Akt/GSK-3b signaling and cardiac compensatory hypertrophy during recovery from heart failure. Eur J Heart Fail 2009;11:739-48
  38. Bugge T, Antalis TM, Wu Q: Type II transmembrane serine proteases. J Biol Chem 2009;284:23177-81.
  39. Naga Prasad SV, Duan ZH, Kumar S, Volinia S, Calin GA, Kotwal A, Moravec CS, Starling RC, Perez DM, Sen S, Wu Q, Plow E, Croce CM, Karnik S: A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. J Biol Chem2009;284:27487-99.
  40. Cui Y, Wu Q, Zhou Y: Iron-refractory iron deficiency anemia: new molecular mechanisms. Kidney Int 2009;76:1137-41.
  41. Guipponi M, Toh M, Tran J, Park D, Hanson K, Ballana E, Kwong D, Cannon P, Wu Q, Gout A, Delorenzi M, Speed TP, Smith RJH, Dahl HH, Petersen M, Teasdale RD, Estivill X, Park WJ, Scott HS: An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss. Human Mutation 2008;29:130-41.
  42. Liao M, Liu Z, Bao J, Zhao Z, Hu J, Feng X, Feng R, Lu Q, Mei Z, Liu Y, Wu Q, Jing Z: A proteomic study of the aortic media in human thoracic aortic dissection: implication for oxidative stress. J Thorac Cardiovasc Surg 2008;136:65-72.
  43. Wang W, Liao X, Fukuda K, Knappe S, Wu F, Dries DL, Qin J, Wu Q: Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity. Circ Res 2008;103:502-8.
  44. Wu Q: The serine protease corin in cardiovascular biology and disease. Front Biosci 2007;12:4179-90.
  45. Guipponi M, Tan J, Cannon P, Donley L, Crewther P, Clarke M, Wu Q, Shepherd RK, Scott HS: Mice deficient for the type II transmembrane serine protease, TMPRSS1/hepsin, exhibit profound hearing loss. Am J Pathol 2007;171:608-16.
  46. Liao X, Wang W, Chen S, Wu Q:  Role of glycosylation in corin zymogen activation. J Biol Chem 2007;282:27728-35.
  47. Wu Q, Parry G: Hepsin and prostate cancer. Front Biosci 2007;12:5052-9.
  48. Xuan JA, Schneider D, Toy P, Lin R, Newton A, Zhu Y, Finster S, Vogel D, Mintzer B, Dinter H, Light D, Parry R, Polokoff M, Whitlow M, Wu Q, Parry G: Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture. Cancer Res 2006;66:3611-9.
  49. Wu Q, Kuo H-C, Deng G: Serine proteases and cardiac function. Biochim Biophys Acta 2005;1751:82-94.
  50. Liang A, Wu F, Tran K, Jones S, Deng G, Ye B, Zhao Z, Snider M, Dole WP, Morser J, Wu Q: Characterization of a small molecule PAI-1 inhibitor, ZK4044. Thromb Res 2005;115:341-50.
  51. Chan J, Knudson O, Wu F, Morser J, Dole WP, Wu Q:  Hypertension in mice lacking the pro-atrial natriuretic peptide convertase, corin. Proc Natl Acad Sci USA 2005;102:785-90.
  52. Dries DL, Victor R, Rame EJ, Cooper RS, Wu X, Zhu X, Leonard D, Ho SI, Wu Q, Post W, Drazner MH: Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension. Circulation 2005;112:2403-10.
  53. Ye B, Chou YL, Karanjawala R, Liang A, Lee W, Lu SF, Shaw KJ, Tseng JL, Wu Q, Zhao Z:  Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1). Bioorg Med Chem Lett 2004;14:761-5.
  54. Knappe S, Wu F, Madlansacay MR, Wu Q: Identification of domain structures in the propeptide of corin essential for the processing of pro-atrial natriuretic peptide. J Biol Chem 2004;279:34464-71.
  55. Tran KL, Lu X,  Lei M, Feng Q, Wu Q: Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium. Am J Physiol Heart Circ Physiol 2004:287:H1625-31.
  56. Dong N, Da Cunha V, Citlowicz A, Wu F, Vincelette J, Larsen B, Wang YX, Ruan C, Dole WP, Morser J, Wu Q, Pan J:  P-selectin-targeting of the fibrin selective thrombolytic Desmodus rotundus salivary plasminogen activator a1. Thromb Haemost 2004;92:956-65.
  57. Wu Q: Type II transmembrane serine proteases. Curr Top Dev Biol 2003;54:167-206.
  58. Knappe S, Wu F, Masikat MR, Morser J, Wu Q: Functional analysis of the transmembrane domain and activation cleavage of human corin: design and characterization of a soluble corin. J Biol Chem 2003;278:52363-70.
  59. Wu F, Wu Q: Corin-mediated processing of pro-atrial natriuretic peptide in human small cell lung cancer cells. Cancer Res 2003;63:8318-22.
  60. Wang Y-X, Dong N, Wu C, Matin-McNulty B, Fitch RM, da Cunha V, Tran K, Vergona R, Sullivan ME, Morser J, Wu Q:  Lipopolysaccharide attenuates thrombolysis in batroxobin-induced lung fibrin deposition but not in ferrous chloride-induced carotid artery thrombus in rats: role of endogenous PAI-1. Thromb Res 2003;111:381-7.
  61. Wu C, Wu F, Pan J, Morser J, Wu Q: Furin-mediated processing of pro-C-type natriuretic peptide. J Biol Chem 2003;278:25847-52.
  62. Ye B, Bauer S, Buckman B, Ghannan A, Griedel B, Khim S, Lee W, Sacchi K, Shaw K, Liang A, Wu Q, Zhao Z: Synthesis and biological evaluation of menthol-based derivatives as inhibitors of plasminogen activator inhibitor. Bioorg Med Chem Lett 2003;13:3361-5.
  63. Wu C, Dong N, da Cunha V, Martin-McNulty B, Tran K, Nagashima M, Wu Q, Morser J, Wang Y: Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) prevents spontaneous fibrinolysis of batroxobin-induced fibrin deposition in rat lungs. Thromb Haemost 2003;90:414-21.
  64. Szabo R, Wu Q, Dickson R, Netzel-Arnett S, Antalis T, Bugge T: Type II transmembrane serine proteases. Thromb Haemost 2003;90:185-93.
  65. Wu Q, Zhao S: Inhibition of PAI-1: a new anti-thrombotic approach. Curr Drug Targets Cardiovasc Haematol Disord 2002;2:27-42.
  66. Pan J, Hinzmann B, Yan W, Wu F, Morser J, Wu Q: Genomic structures of the human and murine corin genes and functional GATA elements in their promoters. J Biol Chem  2002;277:38390-8.
  67. Wu F, Yan W, Pan J, Morser J, Wu Q: Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes. J Biol Chem 2002;277:16900-5.
  68. Wu Q: Gene targeting in hemostasis. hepsin. Front Biosci 2001;6:d192-200.
  69. Yan W, Wu F, Morser J, Wu Q: Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide converting enzyme. Proc Natl Acad Sci USA 2000;97:8525-9.
  70. Yan W, Sheng N, Seto M, Morser J, Wu Q: Corin: a mosaic transmembrane serine protease encoded by a novel cDNA from human heart. J Biol Chem 1999;274:14926-35.
  71. Wu Q, Yu D, Post J, Malks-Miller M, Sadler JE, Morser J: Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease. J Clin Invest 1998;101:321-6.

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