Kenneth K. Wu, MD, PhD
Kenneth K. Wu, M.D., Ph.D., Professor Emeritus

The University of Texas Health Science Center at Houston
Medical School, Department of Internal Medicine
Division of Hematology, Vascular Biology Research Center &
The Institute of Molecular Medicine
6431 Fannin, MSB 5.287   Houston, Texas 77030

 


Academic Office Tel: 713-500-6801
Academic Office Fax: 713-500-6810
E-mail: Kenneth.K.Wu@uth.tmc.edu

 Dr. Wu's research is noted for his novel studies of cyclooxygenase (COX), prostacyclin synthase (PGIS), thromboxane synthase (TXAS) and nitric oxide synthase (eNOS). His laboratory elucidated the mechanisms by which COX-1, COX-2 and eNOS are transcriptionally regulated. His group cloned PGIS and TXAS and characterized their primary structure and structure-function relationship. Work from his laboratory has identified the amino acid residue for heme ligation and substrate binding and characterized the domain function of NOS. To delineate the physiological and clinical relevance of these basic studies, his laboratory has performed a series of experiments to demonstrate the anti-thrombotic benefits of adenovirus-mediated overexpression of COX-1 in damaged arterial wall. He discovered that aspirin and salicylate suppress COX-2 expression in a cell-cycle dependent manner.

Past NIH-funded projects in his laboratory included: (1) Endogenous and pharmacological control of COX-2 and iNOS transcription. This project involved purification of novel compounds, testing their actions on COX-2 and iNOS expression and elucidating their mechanisms of action. Microarray techniques were used to determine the network of genes besides COX-2 and iNOS that are influenced by these compounds; (2) Effects of combined COX-1/PGIS gene overexpression on PGI2 synthesis, intimal hyperplasia, vascular remodeling; (3) Role of genomic polymorphisms of PGIS, eNOS, TXAS, COX and other vasoprotective and prothrombotic genes in predicting risk of coronary heart disease and stroke.

Selected Publications:

Wu, K.K., Hatzakis, H., Lo, S-S, Seong, D.C. and Sanduja, S.K.: Stimulation of de novo synthesis of prostaglandin G/H synthase in human endothelial cells by phorbol ester. J. Biol. Chem., 263: 19043-19047, 1988.

Wu, K.K., Sanduja, R., Tsai, A-L. and Loose-Mitchell, D. Aspirin inhibits the de novo synthesis and the mRNA level of prostaglandin H synthase in cultured endothelial cells. Proc. Natl. Acad. Sci. USA, 88: 2384-2387, 1991.

Xu, X-M, Ohashi, K., Sanduja, S.K., Ruan, K-H, Wang, L-H and Wu, K.K. Enhanced prostacyclin synthesis in endothelial cells by retrovirus-mediated transfer of prostaglandin H synthase cDNA. J. Clin. Invest., 91: 1843-1849, 1993.

Zembowicz, A., Tang, J-L., and Wu, K.K. Transcriptional induction of endothelial nitric oxide synthase type-III by lysophosphatidylcholine. J. Biol. Chem., 270: 17006-17010, 1995.

Zoldhelyi, P., McNatt, J., Xu, X-M., Loose-Mitchell, D., Meidell, R.S., Clubb, F.J., Buja, L.M., Willerson, J.T., Wu, K.K. Prevention of arterial thrombosis by adenovirus-mediated transfer of cyclooxygenase gene. Circulation, 93: 10-17, 1996.

Cieslik, K., Zembowicz, A., Tang, J-L. and Wu, K.K. Transcriptional regulation of endothelial nitric oxide synthase by lysophosphatidylcholine. J. Biol. Chem., 273: 14885-14890, 1998.
Salomaa, V., Matei, C., Aleksic, N., Sansores, L., Folsom, A.R., Juneja, H., Chambless, L.E., Wu, K.K. Soluble thrombomodulin as a predictor of incident coronary heart disease: The ARIC Study. Lancet, 353: 1729-1734, 1999.

Xu, X-M., Sansores-Garcia, L., Chen, X-M., Matijevic-Aleksic, N., Du, M., Wu, K.K. Suppression of inducible cyclooxygenase-2 gene transcription by aspirin and sodium salicylate. Proc. Natl. Acad. Sci. USA, 96: 5292-5297, 1999.

Cieslik, K., Lee, C-M., Tang, J-L., Wu, K.K. Transcriptional regulation of endothelial nitric-oxide synthase by an interaction between casein kinase 2 and protein phosphatase 2A. J. Biol. Chem., 274: 34669-34675, 1999.

Gilroy, D.W., Saunders, M.A., Sansores-Garcia, L., Matijevic-Aleksic, N., Wu, K.K. Cell cycle-dependent expression of cyclooxygenase-2 in human fibroblasts. FASEB J., Express article 10.1096/fj00-0573fje, (published on-line Dec. 8, 2000), FASEB J. (Express Summary), 15: 288-290, 2001.

Cieslik, K., Abrams, C.S., Wu, K.K. Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase gamma/Janus kinase 2/MEK-1-dependent pathway. J. Biol. Chem., 276: 1211-1219, 2001.

Gilroy, D.W., Saunders, M.A., Wu, K.K. COX-2 expression and cell cycle progression in human fibroblasts. Am. J. Physiol. Cell Physiol., 281: C188-194, 2001.

Liou, J.Y., Deng, W.G., Gilroy, D.W., Shyue, S.K., Wu, K.K. Colocalization and Interaction of Cyclooxygenase-2 with Caveolin-1 in Human Fibroblasts. J. Biol. Chem., 276: 34975-34982, 2001.

Deng, W., Saunders, M.A., Gilroy, D.W., He, X-Z., Yeh, H., Zhu, Y., Shtivelband, M.I., Ruan, K-H., Wu, K.K. Purification and characterization of a cyclooxygenase-2 and angiogenesis suppressing factor produced by human fibroblasts. FASEB J., Express article 10.1096/fj.01-0844fje (published online June 7, 2002), FASEB J., 16: 1286-1288, 2002.

 
Internal Medicine General  Medical School   UT-Health Science Center   
Contact  Author  Date of Last Edit