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Qingyu Wu, M.D., Ph.D.Staff
Department of Molecular Cardiology
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Area of general research interest:
Serine proteases of the trypsin superfamily.
Current program:
- Regulation and function of corin
Investigators:
- Chen, Shenghan, Ph.D., Postdoctoral Fellow
- Cui, Yujie, Ph.D., Research Scholar
- Jiang, Jing-Jing, Pre-doctoral Fellow
- Qi, Xiaofei, M.D., Ph.D., Postdoctoral Fellow
- Wang, Wei, M.D., Postdoctoral Fellow
Research:
High blood pressure, also called hypertension, increases the risk for major cardiovascular diseases such as myocardial infarction, stroke, heart failure, and kidney failure. Corin is a serine protease we discovered in the heart. Corin converts pro-atrial natriuretic peptide (ANP) to active ANP, a cardiac hormone essential for maintaining normal blood pressure.
In mice, corin deficiency prevents this pro-ANP to ANP conversion and causes hypertension, demonstrating the importance of corin in producing ANP and controlling blood pressure in vivo. In humans, single nucleotide polymorphisms (SNPs) in the corin gene are associated with an increased risk for hypertension and cardiac hypertrophy in African-Americans.
In functional studies, we found that corin variants caused by SNPs had a low biological activity, suggesting that genetic variants may impair corin function and contribute to hypertension and heart disease in patients.
We use biochemical tools to study the regulation of corin function. We also develop animal models to understand the role of corin in cardiovascular disease.
Key References:
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;274:14926-14935.
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;97:8525-8529.
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;277:16900-16905.
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;277:38390-38398.
Wu Q: Type II transmembrane serine proteases. Curr. Top. Dev. Biol. 2003;54:167-206.
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;278:52363-52370.
Wu C, Wu F, Pan J, Morser J, Wu Q: Furin-mediated processing of pro-C-type natriuretic peptide J. Biol. Chem. 2003;278:25847-25852.
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;279:34464-34471.
Tran KL, Lu X, Lei M, Feng Q, Wu Q: Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium. Am. J. Physiol. 2004:287:H1625-H1631.
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;102:785-790.
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;112:2403-2410.
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;66:3611-3619.
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. Path. 2007;171:608-616.
Liao X, Wang W, Chen S, Wu Q: Role of glycosylation in corin zymogen activation. J. Biol. Chem. 2007;282:27728-27735.
Wu Q. The serine protease corin in cardiovascular biology and disease. Front Biosci 2007;12:4179-4190.
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(5):502-508.
Wu Q, Xu-Cai YO, Chen S, Wang W: Corin: new insights into the natriuretic peptide system. Kidney Int. 2008;Aug 20. [Epub ahead of print]