Tang, Hua, Ph.D.
1993, Ph.D. Biochemistry, Shanghai Medical University, China.
1994 – 1999, Postdoctoral Fellow in Biochemistry, Vanderbilt University, Nashville, TN.
Angiogenesis and endothelial inflammatory activation, including endothelial cytokine production and cell adhesion molecule expression.
Protein kinase D family kinases in angiogenesis and endothelial inflammatory activation.
Angiogenesis is the fundamental physiological process by which new blood vessels are generated from pre-existing vasculature. It plays a crucial role in embryonic development in addition to numerous normal physiological processes. Angiogenesis is critically involved in a wide variety of human diseases including ischemic vascular diseases, tumor growth and metastasis, diabetic retinopathy, age-related macular degeneration, and rheumatoid arthritis. Emerging evidence indicates that angiogenesis also plays a critical role in the development and progression of atherosclerosis, a chronic inflammatory disease of the vessel wall. For these reasons, an understanding of the complex mechanisms that regulate angiogenesis is seen not only as a fundamental problem in human biology but also critical in fulfilling the important goal of biomedical research to develop more specific and efficacious pro- and anti-angiogenesis therapies.
Endothelium inflammatory activation plays a central role in vascular wall inflammation that is associated with various cardiovascular diseases, including atherosclerosis, coronary ischemia, and restenosis. Enhanced production and release of pro-inflammatory cytokines and chemokines from endothelial cells and the endothelial expression of cell adhesion molecules are recognized to play critical roles in the activation of endothelium in inflammation. The broad and long-term goal of our research is to identify targetable (drugable) signal pathways responsible for endothelium inflammatory activation.
Protein kinase D (PKD) family is a newly described serine/threonine protein kinase family that includes PKD1, PKD2, and PKD3. PKD contains a tandem repeat of zinc finger-like cysteine-rich motifs at its N terminus that display high affinity for diacylglycerol or phorbol ester, a pleckstrin homology domain, and a C-terminal catalytic domain that shares homology with the calmodulin-dependent kinases. PKD family kinases can be activated by various pro-angiogenic and pro-inflammatory agonists. By using the advanced technology in molecular biology and biochemistry, we have recently identified that PKD family kinases are critical regulators of angiogenesis and endothelial inflammatory activation. Thus, the long-term goal of our research is to determine the specific roles of each PKD isoform in angiogenesis and endothelium inflammatory activation in vitro and in vivo, including the identity of PKD-targeted genes and protein substrates in endothelial cells.
Selected Papers and Abstracts:
- Hao Q, Wang LP, and Tang H. Vascular endothelial growth factor induces protein kinase D-dependent production of pro-inflammatory cytokines in endothelial cells. Am J Physiol-Cell Physiol (in press) doi:10.1152/ajpcell.00504.2008
- Hao Q, Wang L, Zhao ZJ, Tang H. Identification of protein kinase D2 as a pivotal regulator of endothelial cell proliferation, migration, and angiogenesis. J. Biol. Chem. 2009, 284;799-806.
- Shetty S, Velusamy T, Shetty PK, Tang H, Idell S. Regulation of urokinase receptor expression by protein tyrosine phosphatases. Am J Physiol Lung Cell Mol Physiol. 2007; 292(2):L414-421.
- Hao Q, Rutherford SA, Low B, Tang H. Selective regulation of hydrogen peroxide signaling by receptor tyrosine phosphatase-alpha. Free Radic. Biol. Med. 2006; 41:302-310.
- Hao Q, Rutherford SA, Low B, and Tang H. Suppression of the phosphorylation of receptor tyrosine phosphatase-alpha on the Src-independent site tyrosine 789 by reactive oxygen species. Mol. Pharmacol. 2006; 69:1938-1944.
- Tang H, Hao H, Rutherford SA, Low B, Zhao ZJ. Inactivation of SRC family tyrosine kinases by reactive oxygen species in vivo. J. Biol. Chem. 2005; 280:23918-23925. Corresponding author) (This paper has been featured in Science in the “This Week in Signal Transduction” as a noteworthy contribution to the scientific literature. Sci. STKE . 2005 290; tw240).
- Tang H, Low B, Rutherford SA, Hao Q. Thrombin induces endocytosis of endoglin and type-II TGF- b receptor and down-regulation of TGF- b signaling in endothelial cells. Blood. 2005;105:1977-1985 (Corresponding author).
- Zhao R, Guerrah A, Tang H, Zhao ZJ. Cell surface glycoprotein PZR is a major mediator of concanavalin A-induced cell signaling. J. Biol. Chem. 2002;277:7882-7888.
- Tang H, Hao Q, Fitzgerald T, Sasaki T, Landon EJ, and Inagami T. Pyk2/CAKbeta tyrosine kinase activity-mediated angiogenesis of pulmonary vascular endothelial cells. J. Biol. Chem. 2002;277:5441-5447 (Corresponding author).
- Satoh K, Ichihara K, Landon EJ, Inagami T, Tang H. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors block calcium-dependent tyrosine kinase Pyk2 activation by angiotensin II in vascular endothelial cells. involvement of geranylgeranylation of small G protein Rap1. J. Biol. Chem. 2001;276:15761-15767 (Corresponding author).
- Tang H, Nishishita T, Fitzgerald T, Landon EJ, Inagami T. Inhibition of AT1 receptor internalization by concanavalin A blocks angiotensin II-induced ERK activation in vascular smooth muscle cells. Involvement of epidermal growth factor receptor proteolysis but not AT1 receptor internalization. J. Biol. Chem. 2000; 275: 13420-13426.