Translational Approach to Vascular Biology Dr. James Liao’s laboratory takes a multi-disciplinary, translational approach to vascular biology. He is interested in conditions, factors, and signaling molecules, which regulate endothelial nitric oxide synthase (eNOS) in vascular disease. This has led to the discovery of eNOS regulation by Rho/Rho-kinase and PI3K/Akt pathway in his laboratory. Indeed, some of the mechanisms underlying the pleiotropic effects of statins or nongenomic effects of steroid hormones were initially uncovered and characterized in his laboratory. His laboratory continues to work in these areas. Furthermore, Dr. Liao is interested in the role of other endothelium-derived factors such as epoxyeicosatrienoic acids (EETs) in regulating vascular function.
Ongoing projects in his laboratory include:
Studying the role of heterotrimeric G-proteins in mediating NO release in vascular endothelial cells and the inhibitory effects of atherogenic lipoporteins.
Investigating the mechanisms by which NO decreases the expression adhesion molecules and the pro-inflammatory transcription factor, NF-kB.
Determining the direct or cholesterol-independent vascular effects of HMG-CoA reductase inhibitors or statins on eNOS and vascular function.
Investigating the role of Rho kinases (ROCKs) on eNOS in vascular disease.
Studying the molecular signaling mechanisms by which steroid hormones, in particular estrogen and glucocorticoids, activate eNOS.
A link to Dr. Liao's laboratory can be found here: http://vmru.bwh.harvard.edu/
References:
Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 1999;285:1276-9.
Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 2000;407:538-41.
Takemoto M, Node K, Nakagami H, Liao Y, Grimm M, Takemoto Y, Kitakaze M, Liao JK. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J. Clin. Invest. 2001;108:1429-37.
Hafezi-Moghadam A, Simoncini T, Yang Z, Limbourg F, Plumier JC, Rebsamen M, Hsieh CM, Chui DS, Thomas KL, Prorock AJ, Laubach VE, French BA, Ley K, Liao JK. Acute cardiovascular protective effects of corticosteroids mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nature Med. 2002;8:473-9.
Rikitake Y, Oyama N, Wang CY, Noma K, Satoh M, Kim HH, Liao JK. Decreased perivascular fibrosis but not cardiac hypertrophy in ROCK+/- haploinsufficient mice. Circulation 2005;112:2959-65.
Hiroi Y, Kim HH, Ying H, Furuya F, Huang Z, Simoncini T, Noma K, Ueki K, Nguyen NH, Scanlan T, Moskowitz MA, Cheng SY, Liao JK. Rapid nongenomic actions of thyroid hormone. Proc. Natl. Acad. Sci. USA 2006;103:14104-9.
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