BADERC-Zhijun Luo

James K. Liao, MD

Vascular Cell Signaling
The research program is focused on signaling pathways that govern vascular function, in both normal and diseased states. The program attempts to translate basic findings in the vascular wall to therapeutic applications in patients with cardiovascular disease. In the process, the function of endothelial nitric oxide synthase (eNOS) will be characterized with regards to its regulation by G-proteins, lipoproteins, and HMG-CoA reductase inhibitors (statins). This has led to the discovery of eNOS upregulation by statins via the Rho/Rho kinase (ROCK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In addition, research effort is aimed at identifying the role of Rac1 and Notch1 in angiogenesis and to delineate a rapid "nongenomic" effect of steroid hormone through cross-coupling to the PI3K/Akt pathway. Presently, our research efforts are focused on the pathophysiological role of ROCK signaling in cardiovascular, neurological, and metabolic diseases using conditional ROCK1 and ROCK2 KO mice.

In addition, Other research interests include:
1. the role of Cytochrome P450 (CYP) 2J2 and epoxyeicosatrienoic acids (EETs) in regulating cardiovascular function and investigating the expression and activities of ROCKs and CYP2J2 in patients with cardiovascular risk factors and disease.

2. Studying the role of heterotrimeric G-proteins and EETs in regulating vascular function and response to injury (J Clin Invest 1993;92:2168-72; J Clin Invest 1995;95:1457-63; J Biol Chem 1997;272:19601-8; Science 1999;285:1276-9; J Biol Chem 2001;276:15983-9; Circ Res 2002;90:1020-7; Circulation 2004;110:2132-6)

3. Investigating the mechanisms by which NO and vascular cell adhesion molecules regulate vascular inflammation (J Clin Invest 1995;96:60-8; J Clin Invest 1995;96:2661-6; J Biol Chem 1995;270:17050-5; J Immunol 1997;159:2418-23).

4. Determining the cholesterol-independent vascular effects of statins on vascular function and in stroke protection (Circulation 1998;97:1129-35; J Biol Chem 1998;273:24266-71; Proc Natl Acad Sci USA 1998;95:8880-5; J Clin Invest 2000;106:15-24).

5. Investigating the role of ROCKs, Rac1, and Notch1 in vascular inflammation, angiogenesis, and atherosclerosis, cardiac hypertrophy, heart failure, and stroke (Circulation 2005;112:2959-65; Proc Natl Acad Sci USA 2006;103:7432-7; Circulation 2005;111:1826-32; Circ Res 2007;100:70-8; Proc Natl Acad Sci USA 2008;105:4856-61; J Clin Invest 2008;118:1632-44; Circ Res 2008;103:360-8; FASEB J 2008;22:3561-70; Sci Signal 2008;1:ra14; Sci Signal 2009;2:ra10).

6. Studying the mechanisms by which steroid hormones regulate PI3K/Akt/eNOS pathway and vascular function (Nature 2000;407:538-41; Nat Med 2002;8:473-9; J Clin Invest 2002;110:1729-38; Mol Cell Biol 2003;23:5726-37; J Clin Invest 2006;116:334-43; Proc Natl Acad Sci USA 2006;103:14104-9; Sci Signal 2009;2:ra11).






			James K. Liao, MD Vascular Cell Signaling The research program is focused on signaling pathways that govern vascular function, in both normal and diseased states. The program attempts to translate basic findings in the vascular wall to therapeutic applications in patients with cardiovascular disease. In the process, the function of endothelial nitric oxide synthase (eNOS) will be characterized with regards to its regulation by G-proteins, lipoproteins, and HMG-CoA reductase inhibitors (statins). This has led to the discovery of eNOS upregulation by statins via the Rho/Rho kinase (ROCK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In addition, research effort is aimed at identifying the role of Rac1 and Notch1 in angiogenesis and to delineate a rapid "nongenomic" effect of steroid hormone through cross-coupling to the PI3K/Akt pathway. Presently, our research efforts are focused on the pathophysiological role of ROCK signaling in cardiovascular, neurological, and metabolic diseases using conditional ROCK1 and ROCK2 KO mice. In addition, Other research interests include: 1. the role of Cytochrome P450 (CYP) 2J2 and epoxyeicosatrienoic acids (EETs) in regulating cardiovascular function and investigating the expression and activities of ROCKs and CYP2J2 in patients with cardiovascular risk factors and disease. 2. Studying the role of heterotrimeric G-proteins and EETs in regulating vascular function and response to injury (J Clin Invest 1993;92:2168-72; J Clin Invest 1995;95:1457-63; J Biol Chem 1997;272:19601-8; Science 1999;285:1276-9; J Biol Chem 2001;276:15983-9; Circ Res 2002;90:1020-7; Circulation 2004;110:2132-6) 3. Investigating the mechanisms by which NO and vascular cell adhesion molecules regulate vascular inflammation (J Clin Invest 1995;96:60-8; J Clin Invest 1995;96:2661-6; J Biol Chem 1995;270:17050-5; J Immunol 1997;159:2418-23). 4. Determining the cholesterol-independent vascular effects of statins on vascular function and in stroke protection (Circulation 1998;97:1129-35; J Biol Chem 1998;273:24266-71; Proc Natl Acad Sci USA 1998;95:8880-5; J Clin Invest 2000;106:15-24). 5. Investigating the role of ROCKs, Rac1, and Notch1 in vascular inflammation, angiogenesis, and atherosclerosis, cardiac hypertrophy, heart failure, and stroke (Circulation 2005;112:2959-65; Proc Natl Acad Sci USA 2006;103:7432-7; Circulation 2005;111:1826-32; Circ Res 2007;100:70-8; Proc Natl Acad Sci USA 2008;105:4856-61; J Clin Invest 2008;118:1632-44; Circ Res 2008;103:360-8; FASEB J 2008;22:3561-70; Sci Signal 2008;1:ra14; Sci Signal 2009;2:ra10). 6. Studying the mechanisms by which steroid hormones regulate PI3K/Akt/eNOS pathway and vascular function (Nature 2000;407:538-41; Nat Med 2002;8:473-9; J Clin Invest 2002;110:1729-38; Mol Cell Biol 2003;23:5726-37; J Clin Invest 2006;116:334-43; Proc Natl Acad Sci USA 2006;103:14104-9; Sci Signal 2009;2:ra11).