James K. Liao

Director, Cardiovascular Research Laboratory

Harold H. Hines Professor of Medicine

Chief, Section of Cardiology, Department of Medicine; Medical Director, Heart & Vascular Center

Director, Physician Scientist Development Program (PSDP)

 

Dr. Liao’s research focuses on the role of statins in stroke and atherosclerosis specifically the signaling pathways that govern vascular function, in both normal and diseased states. His laboratory work seeks to translate basic findings in the vascular wall to therapeutic applications in patients with vascular diseases. He has characterized the function of endothelial nitric oxide synthase (eNOS) with regards to its regulation by G- proteins, lipoproteins, HMG-CoA reductase inhibitors (statins), and steroid hormones. This has led to the discovery of eNOS upregulation by statin via the Rho/Rho kinase (ROCK) and phosphatidylinositol 3-kinase (P13K) /protein kinase B (Akt) pathway. Dr. Liao coined the term “pleiotropic” effects on statins to help recognize and emphasize the clinical importance of non-cholesterol mechanisms of statins on endothelial function and in stroke protection. In addition, Dr. Liao is interested in the role of Rac1 and Notch1 in angiogenesis and stroke and was the first to delineate a rapid “nongenomic” effect of steroid hormone through cross coupling to the P13K/Akt pathway.

Phone number: (773) 702-1234 | E-mail: jliao@medicine.bsd.uchicago.edu

Selected Peer-reviewed Publications (Selected from >250 peer-reviewed publications)

 

1. Liao JK, Homcy CJ. The G proteins of the G alpha i and G alpha q family couple the bradykinin receptor to the release of endothelium-derived relaxing factor. J Clin Invest 1993;92:2168-72.

 

2. Liao JK. Inhibition of Gi proteins by low density lipoprotein attenuates bradykinin-stimulated release of endothelial-derived nitric oxide. J Biol Chem 1994;269:12987-92.

 

3. Liao JK, Clark SL. Regulation of G-protein alpha i2 subunit expression by oxidized low-density lipoprotein. J Clin Invest 1995;95:1457-63.

 

4. Liao JK, Zulueta JJ, Yu FS, Peng HB, Cote CG, Hassoun PM. Regulation of bovine endothelial constitutive nitric oxide synthase by oxygen. J Clin Invest 1995;96:2661-6.

 

5. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA, Shin WS, Liao JK. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995;96:60-8.

 

6. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998;97:1129-35.

 

7. Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. Stroke protection by 3- hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 1998;95:8880-5.

 

8. 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(5431):1276-9.

 

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.

 

10. Laufs U, Endres M, Stagliano N, Amin-Hanjani S, Chui DS, Yang SX, Simoncini T, Yamada M, Rabkin E, Allen PG, Huang PL, Böhm M, Schoen FJ, Moskowitz MA, Liao JK. Neuroprotection mediated by changes in the endothelial actin cytoskeleton. J Clin Invest 2000;106:15-24.

 

11. 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.

 

12. Simoncini T, Genazzani AR, Liao JK. Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene. Circulation 2002;105:1368-73.

 

13. Hafezi-Moghadam A, Simoncini T, Yang Z, Limbourg FP, Plumier JC, Rebsamen MC, Hsieh CM, Chui DS, Thomas KL, Prorock AJ, Laubach VE, Moskowitz MA, French BA, Ley K, Liao JK. Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat Med 2002;8:473-9.

 

14. Limbourg FP, Huang Z, Plumier JC, Simoncini T, Fujioka M, Tuckermann J, Schütz G, Moskowitz MA, Liao JK. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest 2002;110:1729-38.

 

15. Sun J, Liao JK. Functional interaction of endothelial nitric oxide synthase with a voltage-dependent anion channel. Proc Natl Acad Sci USA 2002;99:13108-13.

 

16. Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK. Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 2002;106:57-62.

 

17. Kawasaki K, Smith RS, Hsieh CM, Sun J, Chao J, Liao JK. Activation of the phosphatidylinositol 3- kinase/protein kinase Akt pathway mediates nitric oxide-induced endothelial cell migration and angiogenesis. Mol Cell Biol 2003;23:5726-37.

 

18. Node K, Fujita M, Kitakaze M, Hori M, Liao JK. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 2003;108:839-43.

 

19. Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, Node K, Börgel J, Mügge A, Lindpaintner K, Huesing A, Maisch B, Zeldin DC, Liao JK. Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation 2004;110:2132-6.

 

20. Limbourg FP, Takeshita K, Radtke F, Bronson RT, Chin MT, Liao JK. Essential role of endothelial Notch1 in angiogenesis. Circulation 2005;111:1826-32.

 

21. Rikitake Y, Liao JK. Rho-kinase mediates hyperglycemia-induced plasminogen activator inhibitor-1 expression in vascular endothelial cells. Circulation 2005;111:3261-8.

 

22. Rikitake Y, Oyama N, Wang CY, Noma K, Satoh M, Kim HH, Liao JK. Decreased perivascular fibrosis but not cardiac hypertrophy in ROCK1+/- haploinsufficient mice. Circulation 2005;112:2959-65.

 

23. Satoh M, Ogita H, Takeshita K, Mukai Y, Kwiatkowski DJ, Liao JK. Requirement of Rac1 in the development of cardiac hypertrophy. Proc Natl Acad Sci USA 2006;103:7432-7.

 

24. Mukai Y, Rikitake Y, Shiojima I, Wolfrum S, Satoh M, Takeshita K, Hiroi Y, Salomone S, Kim HH, Benjamin LE, Walsh K, Liao JK. Decreased vascular lesion formation in mice with inducible endothelialspecific expression of protein kinase Akt. J Clin Invest 2006;116:334-43.

 

25. Hiroi Y, Kim HH, Ying H, Furuya F, Huang Z, Simoncini T, Noma K, Ueki K, Nguyen NH, Scanlan TS, Moskowitz MA, Cheng SY, Liao JK. Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci USA 2006;103:14104-9.

 

26. Liu PY, Chen JH, Lin LJ, Liao JK. Increased Rho kinase (ROCK) activity in a Taiwanese population with metabolic syndrome. J Am Coll Cardiol 2007;49:1619-24.

 

27. Satoh M, Matter CM, Ogita H, Takeshita K, Wang CY, Dorn GW, Liao JK. Inhibition of apoptosis-regulated signaling kinase-1 and prevention of congestive heart failure by estrogen. Circulation 2007;115:3197-204.

 

28. Noma K, Rikitake Y, Oyama N, Yan G, Alcaide P, Liu P-Y, Wang H, Ahl D, Sawada N, Okamoto R, Hiroi, Shimizu K, Luscinskas FW, Sun J, Liao JK. ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. J Clin Invest 2008;118:1632-44.

 

29. Sawada N, Kim HH, Moskowitz MA, Liao JK. Rac1 is a critical mediator of endothelium-derived neurotrophic activity. Sci Signal 2009;2:ra10.

 

30. Wang CY, Kim HH, Hiroi Y, Sawada N, Salomone S, Benjamin LE, Walsh K, Moskowitz MA, Liao JK. Obesity increases vascular senescence and susceptibility to ischemic injury through chronic activation of Akt/mTOR. Sci Signal 2009;2:ra11.

 

31. Li Y, Takeshita K, Liu PY, Satoh M, Oyama N, Mukai Y, Chin MT, Krebs L, Kotlikoff MI, Radtke F, Gridley T, Liao JK. Smooth muscle notch 1 mediates neointimal formation following vascular injury. Circulation 2009;119:2686-92.

 

32. Li Y, Hiroi Y, Ngoy S, Okamoto R, Noma K, Wang CY, Wang HW, Zhou Q, Radtke F, Liao R, Liao JK. Notch1 in bone marrow derived cells mediates cardiac repair after myocardial infarction. Circulation 2011;123:866-76.

 

33. Zhou Q, Yu M, Shoji T, Han X, Kaminski K, Oh GT, Ongusaha PP, Zhang K, Schmitt H, Moser M, Bode C, Liao JK. ROCK2 deficiency in bone marow-derived cells leads to increased cholesterol efflux and decreased atherosclerosis. Circulation 2012;128:2236-47.

 

34. Okamoto R, Li Y, Noma K, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK. FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2. FASEB J. 2013;27:1439-49.

 

35. Zee RY, Wang QM, Chasman DI, Ridker PM, Liao JK. Gene variations of ROCKs and risk of ischaemic stroke: the Women’s Genome Health Study. Clin Sci (Lond) 2014;126:829-35.

 

36. Liu PY, Lee PT, Chang WT, Tai YL, Chao TH, Lee CH, Li YH, Chen JH, Tsai LM, Liao JK. Evidence of pleiotrophy by statins: leukocyte Rho kinase (ROCK) activity and pretreated statin before percutaneous coronary interventions and clinical vascular outcome predictors. Int J Cardiol. 2014;178:250-3.

 

37. Zhou Q, Gensch C, Keller C, Schmitt H, Esser J, Moser M, Liao JK. MnTBAP stimulates angiogenic functions in endothelial cells through mitofusin-1. Vascul Pharmacol. 2015;72:163-71.

 

38. Tabit CE, Chen P, Kim GH, Fedson SE, Sayer G, Coplan MJ, Jeevanandam V, Uriel N, Liao JK. Elevated angiopoietin-2 level in patients with continuous-flow left ventricular assist devices leads to altered angiogenesis and is associated with higher nonsurgical bleeding. Circulation 2016;134:141-52.