James K Liao

Tokyo Medical and Dental University, Edo, Tōkyō, Japan

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Publications (177)1172.64 Total impact

  • International journal of cardiology. 07/2014;
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    ABSTRACT: Cardiovascular diseases are associated with chronic activation of Rho-associated kinase. Rho-associated kinase activity is significantly correlated with endothelial function and Framingham risk score. However, there is no information on the prognostic value of Rho-associated kinase activity. We evaluated Rho-associated kinase activity in peripheral leukocytes by Western blot analysis in 633 subjects who underwent health-screening examination at Hiroshima University Hospital. We assessed the associations between Rho-associated kinase activity and first major cardiovascular events (death from cardiovascular causes, myocardial infarction, and stroke), death from cardiovascular causes, acute myocardial infarction, stroke, revascularization (percutaneous coronary intervention, coronary artery bypass grafting), and hospitalization for heart failure. During a median period of 42.0 months (interquartile range, 24.4-56.6 months) of follow-up, 29 subjects died (10 from cardiovascular causes), 2 myocardial infarction, 20 revascularization, 15 stroke, and 17 hospitalization for heart failure. After adjustment for age, sex, cardiovascular risk factors, and other relevant variables, Rho-associated kinase activity remained a strong independent indicator of first major cardiovascular events (hazard ratio, 2.19; 95% confidence interval, 1.35-3.70; P=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95% confidence interval, 1.18-6.60; P=0.002), stroke (hazard ratio, 2.14; 95% confidence interval, 1.24-3.86; P=0.006), and revascularization (hazard ratio, 2.68; 95% confidence interval, 1.60-4.66; P<0.001). Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.
    Hypertension 12/2013; · 6.87 Impact Factor
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    ABSTRACT: Recent animal and human studies have demonstrated the importance of RhoA/Rho-associated kinases (ROCKs) pathway in ischemic stroke (IsST). Whether the genetic variation within ROCKs-associated genes modulates IsST risk remains elusive. The association between 66 tag-SNPs (tSNPs) of 3 ROCKs-associated genes (ROCK1, ROCK2 and ARHGEF10) and incident IsST was investigated in 23,294 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cancer and cardiovascular disease at baseline. During a 15-year follow-up period, 323 participants developed a first ever IsST. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and IsST risk assuming an additive genetic model. Haplotype-block analysis was also performed. A total of ten tSNPs were associated with IsST risk (three in ARHGEF10, and seven in ROCK1; all p<0.050). Further investigation using the haplotype-block analysis revealed similar significant association of pre-specified haplotypes of ROCK1 with IsST risk (p=0.005). If corroborated in other large prospective studies, the present findings suggest that genetic variation within the ROCKs-associated pathway gene loci examined, in particular, the ROCK1 gene variation may influence IsST risk.
    Clinical Science 12/2013; · 4.86 Impact Factor
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  • Naoki Sawada, James K Liao
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    ABSTRACT: Significance: The HMG-CoA reductase inhibitors or statins are important therapeutic agents for lowering serum cholesterol levels. However, recent studies suggest that statins may exert atheroprotective effects beyond cholesterol lowering. These so-called "pleiotropic effects" include effects of statins on vascular and inflammatory cells. Thus, it is important to understand whether other signaling pathways that are involved in atherosclerosis could be targets of statins, and if so, whether individuals with "over-activity" of these pathways could benefit from statin therapy, regardless of serum cholesterol level. Recent Advances: Statins inhibit the synthesis of isoprenoids, which are important for the function of the Rho/Rho-associated coiled-coil containing kinase (ROCK) pathway. Indeed, recent studies suggest that inhibition of the Rho/ROCK pathway by statins could lead to improved endothelial function and decreased vascular inflammation and atherosclerosis. Thus, the Rho/ROCK pathway has emerged as an important target of statin therapy for reducing atherosclerosis and possibly cardiovascular disease. Critical Issues: Because atherosclerosis is both a lipid and an inflammatory disease, it is important to understand how inhibition of Rho/ROCK pathway could contribute to statins' anti-atherosclerotic effects. Future Directions: The role of ROCKs (ROCK1 and ROCK2) in endothelial, smooth muscle, and inflammatory cells needs to be determined in the context of atherogenesis. This could lead to the development of specific ROCK1 or ROCK2 inhibitors, which could have greater therapeutic benefits with less toxicity. Also, clinical trials will need to be performed to determine whether inhibition of ROCKs, with and without statins, could lead to further reduction in atherosclerosis and cardiovascular disease.
    Antioxidants & Redox Signaling 08/2013; · 8.20 Impact Factor
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    ABSTRACT: OBJECTIVE: The pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) independent of cholesterol-lowering effects are thought to be mediated through inhibition of the Rho/Rho-kinase pathway. However, we have previously demonstrated that the pleiotropic effects of regular-dose statins are mediated mainly through inhibition of the Rac1 signaling pathway rather than the Rho/Rho-kinase pathway, although the molecular mechanisms of the selective inhibition of the Rac1 signaling pathway by regular-dose statins remain to be elucidated. In this study, we tested our hypothesis that small GTP-binding protein GDP dissociation stimulator (SmgGDS) plays a crucial role in the molecular mechanisms of the Rac1 signaling pathway inhibition by statins in endothelial cells. APPROACH AND RESULTS: In cultured human umbilical venous endothelial cells, statins concentration-dependently increased SmgGDS expression and decreased nuclear Rac1. Statins also enhanced SmgGDS expression in mouse aorta. In control mice, the protective effects of statins against angiotensin II-induced medial thickening of coronary arteries and fibrosis were noted, whereas in SmgGDS-deficient mice, the protective effects of statins were absent. When SmgGDS was knocked down by its small interfering RNA in human umbilical venous endothelial cells, statins were no longer able to induce Rac1 degradation or inhibit angiotensin II-induced production of reactive oxygen species. Finally, in normal healthy volunteers, statins significantly increased SmgGDS expression with a significant negative correlation between SmgGDS expression and oxidative stress markers, whereas no correlation was noted with total or low-density lipoprotein-cholesterol. CONCLUSIONS: These results indicate that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.34 Impact Factor
  • Ming Dong, Xin Jiang, James K Liao, Bryan P Yan
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    ABSTRACT: BACKGROUND: Recent evidence suggests that Rho-kinase (ROCK) plays an important role in the pathogenesis of atherosclerosis and a marker of atherosclerotic burden. Polyvascular disease with concomitant peripheral arterial disease (PAD) and coronary artery disease (CAD) is common and associated with a worse prognosis. The aim of this study was to evaluate ROCK activity as a marker of polyvascular disease. HYPOTHESIS: METHODS: We retrospectively analyzed patients undergoing coronary angiography at our institution between February 2009 and May 2009. Patients with only CAD (n = 40) defined by coronary artery stenosis of ≥50% by angiography, only PAD (n = 40) defined by an ankle brachial index (ABI) <0.9, and combined CAD/PAD (n = 40) were matched by age and sex to control patients (n = 40) without CAD or PAD. ROCK activity was determined by phosphorylation of the myosin binding subunit in leukocytes and then compared between each group. Multivariate analysis was used to determine independent predictors of polyvascular disease. Discriminative ability of elevated ROCK activity was assessed using receiver operator characteristics (ROC) curves. RESULTS: Patients (age 68 ± 12 years, 79% male) with CAD, PAD, and CAD/PAD had a mean ABI of 1.08, 0.62, and 0.65, respectively, compared to 1.08 in the control group. There was an incremental increase in ROCK activity in patients with CAD (4.61 ± 2.11), PAD (4.27 ± 1.39), and CAD/PAD (5.96 ± 1.94) compared to control (2.40 ± 0.43) (all P < 0.05). ROCK activity (odds ratio: 4.53, 95% confidence interval: 1.26-6.30) was an independent predictor of polyvascular disease. The ROCK cutoff value of 4.85 had a sensitivity of 72.7% and a specificity of 65.7%, with an area under ROC curve of 0.71 for polyvascular disease. CONCLUSIONS: Patients with concomitant peripheral and coronary arterial disease are associated with increased Rho-kinase activity. Rho-kinase activity may be a potential marker of atherosclerotic burden for patients with polyvascular disease.
    Clinical Cardiology 03/2013; · 1.83 Impact Factor
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    ABSTRACT: The Rho-associated coiled-coil containing kinases, ROCK1 and ROCK2, are important regulators of cell shape, migration, and proliferation through effects on the actin cytoskeleton. However, it is not known whether ROCK2 plays an important role in the development of cardiac hypertrophy. To determine whether the loss of ROCK2 could prevent cardiac hypertrophy, cardiomyocyte-specific ROCK2-null (c-ROCK2(-/-)) were generated using conditional ROCK2(flox/flox) mice and α-myosin heavy-chain promoter-driven Cre recombinase transgenic mice. Cardiac hypertrophy was induced by Ang II infusion (400 ng/kg/min, 28 d) or transverse aortic constriction (TAC). Under basal conditions, hemodynamic parameters, cardiac anatomy, and function of c-ROCK2(-/-) mice were comparable to wild-type (WT) mice. However, following Ang II infusion or TAC, c-ROCK2(-/-) mice exhibited a substantially smaller increase in heart-to-body weight ratio, left ventricular mass, myocyte cross-sectional area, hypertrophy-related fetal gene expression, intraventricular fibrosis, cardiac apoptosis, and oxidative stress compared to control mice. Deletion of ROCK2 in cardiomyocytes leads to increased expression of four-and-a-half LIM-only protein-2 (FHL2) and FHL2-mediated inhibition of serum response factor (SRF) and extracellular signal-regulated mitogen-activated protein kinase (ERK). Knockdown of FHL2 expression in ROCK2-deficient cardiomyocytes or placing ROCK2-haploinsufficient (ROCK2(+/-)) mice on FHL2(+/-)-haploinsufficient background restored the hypertrophic response to Ang II. These results indicate that cardiomyocyte ROCK2 is essential for the development of cardiac hypertrophy and that up-regulation of FHL2 may contribute to the antihypertrophic phenotype that is observed in cardiac-specific ROCK2-deficient mice.-Okamoto, R., Li, Y., Noma, K., Hiroi, Y., Liu, P.-Y., Taniguchi, M., Ito, M., Liao, J. K. FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.
    The FASEB Journal 12/2012; · 5.70 Impact Factor
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    ABSTRACT: Resuscitation from hemorrhagic shock induces endothelial dysfunction and activates inflammatory cascades leading to organ damage. Following restoration of blood flow to ischemic vascular beds, leukocyte-endothelium interactions leading to leukocyte infiltration into the vascular wall occur very early due, in part, to the loss of endothelium-derived nitric oxide (NO). The mechanism by which ischemia-reperfusion injury impairs endothelium-derived NO is not completely understood. We hypothesized that inhibition of Rho-kinase could exert beneficial effects following hemorrhagic shock by preserving endothelial function and attenuating leukocyte trafficking in the microcirculation. Using intravital microscopy, we found that resuscitation from hemorrhage acutely increased the number of rolling and adherent leukocytes in the mouse splanchnic microcirculation. Treatment of mice with the Rho-kinase inhibitor fasudil, markedly attenuated leukocyte-endothelium interaction in response to hemorrhage/reinfusion. The beneficial effect of fasudil was not observed in endothelial nitric oxide synthase (eNOS)(-/-) mice. In conclusion, inhibition of Rho-kinase prevents inflammatory leukocyte trafficking in the microcirculation via an eNOS-dependent mechanism. Our data support a role for Rho-kinase inhibitors in the treatment of ischemia-reperfusion injury.
    Vascular Medicine 09/2012; · 1.62 Impact Factor
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    ABSTRACT: BACKGROUND: Macrophages play a central role in the development of atherosclerosis. However, the signaling pathways that regulate their function are not well understood. The Rho-associated coiled-coil containing kinases (ROCK1 and ROCK2) are serine-threonine protein kinases that are involved in the regulation of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and bone marrow (BM)-derived cells mediates atherogenesis. However, a similar role for ROCK2 in the pathogenesis of atherosclerosis has not been determined. METHODS AND RESULTS: The BMs from wild-type (WT), ROCK2(+/-) and ROCK2(-/-) mice were transplanted into irradiated recipient LDLr(-/-) mice and atherosclerosis was induced with a 16-week high-cholesterol diet. Compared to WT BM transplanted (BMT) mice, ROCK2(+/-) BMT and ROCK2(-/-) BMT mice showed substantially less lipid accumulation in the aorta (8.46 ± 1.42% and 9.80 ± 2.34% vs. 15.64 ± 1.89%, p<0.01 for both) and decreased atherosclerotic lesions in the subaortic sinus (158.1 ± 44.4 and 330.1 ± 109.5 x10(3)μm(2) vs. 520.2 ± 125.7 x10(3)μm(2), p<0.01 for both). These findings correlated with decreased foam cell formation (2.27 ± 0.57 vs. 4.10 ± 0.3, p<0.01) and increased cholesterol efflux (17.65 ± 0.6 vs. 9.75 ± 0.8, p<0.05) in ROCK2-deficient mice that are mediated, in part, through the PPARγ-LXR-ABCA-1 pathway in macrophages. CONCLUSIONS: ROCK2 contributes to atherosclerosis, in part, by inhibiting PPARγ-mediated reverse cholesterol transport in macrophages, which contributes to foam cell formation. These findings suggest that inhibition of ROCK2 in macrophages may have therapeutic benefits in preventing the development of atherosclerosis.
    Circulation 09/2012; · 15.20 Impact Factor
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    ABSTRACT: The serine/threonine protein kinase paralogs ROCK1 & 2 have been implicated as essential modulators of angiogenesis; however their paralog-specific roles in endothelial function are unknown. shRNA knockdown of ROCK1 or 2 in endothelial cells resulted in a significant disruption of in vitro capillary network formation, cell polarization, and cell migration compared to cells harboring non-targeting control shRNA plasmids. Knockdowns led to alterations in cytoskeletal dynamics due to ROCK1 & 2-mediated reductions in actin isoform expression, and ROCK2-specific reduction in myosin phosphatase and cofilin phosphorylation. Knockdowns enhanced cell survival and led to ROCK1 & 2-mediated reduction in caspase 6 and 9 cleavage, and a ROCK2-specific reduction in caspase 3 cleavage. Microarray analysis of ROCK knockdown lines revealed overlapping and unique control of global transcription by the paralogs, and a reduction in the transcriptional regulation of just under 50% of VEGF responsive genes. Finally, paralog knockdown in xenograft angiosarcoma tumors resulted in a significant reduction in tumor formation. Our data reveals that ROCK1 & 2 exhibit overlapping and unique roles in normal and dysfunctional endothelial cells, that alterations in cytoskeletal dynamics are capable of overriding mitogen activated transcription, and that therapeutic targeting of ROCK signaling may have profound impacts for targeting angiogenesis.
    Current Molecular Medicine 08/2012; · 4.20 Impact Factor
  • Qing Mei Wang, James K Liao
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    ABSTRACT: Introduction: Stroke is the third leading cause of death and a major cause of long-term disability in the adult population. Growing evidence suggests that inflammation may play an important role in the evolution of stroke. Because Rho-associated coiled-coil containing kinases (ROCKs) are important mediators of inflammation, they may contribute to stroke and stroke recovery. Areas covered: The pathophysiological role of ROCKs in mediating inflammation at different phases of stroke, and the therapeutic opportunities for stroke prevention and stroke treatment with ROCK inhibitors will be discussed. Expert opinion: Inflammation is a double-edged sword during the evolution of stroke. Immunomodulation might provide a novel therapeutic approach for stroke prevention and stroke treatment. ROCK plays an important role in mediating the inflammatory response following vascular injury as well as platelet activation and thrombus formation. ROCK inhibitors have been shown to be beneficial in stroke prevention, acute neuroprotection and chronic stroke recovery by affecting inflammatory-mediated platelet and endothelial function, smooth muscle contraction and neuronal regeneration. Thus, ROCK-mediated inflammation could be a potential therapeutic target for stroke prevention and stroke treatment. However, the mechanism by which ROCKs regulate the inflammatory response is unclear, and the role of the two ROCK isoforms in stroke and stroke recovery remains to be determined.
    Expert opinion on therapeutic targets 08/2012; 16(10):1013-25. · 3.72 Impact Factor
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    ABSTRACT: BACKGROUND: Recent experimental evidence suggests that the Rho/Rho-kinase (ROCK) system may play an important role in the pathogenesis of acute coronary syndrome (ACS) but there are little clinical data. This study examined if ROCK activity is increased in patients with acute coronary syndrome and if ROCK activity predicts long-term cardiovascular event. METHOD: Blood samples were collected from 188 patients within 12h after admission for ACS (53% men; aged 70±13) and from 61 control subject. The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) from presentation within around 2years (mean:14.4±7.2months; range: 0.5 to 26months). RESULTS: ROCK activity increased in ST elevation myocardial infarction (STEMI, n=90) (3.33±0.93), non-STEMI (NSTEMI, n=68) (3.37±1.04) and unstable angina (UA, n=30) (2.53±0.59) groups when compared with disease controls (n=31) (2.06±0.38, all p<0.001) and healthy controls (n=30) (1.54±0.43, all p<0.001). There were 24 deaths, 34 readmissions with ACS and 15 admissions with CHF within 2years. Patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high ROCK activity on admission had a five-fold risk of a cardiovascular event (RR: 5.156; 95% CI: 2.180-12.191) when compared to those with low NT-proBNP and low ROCK activity. CONCLUSION: ROCK activity was increased in patients with ACS, particularly in those with myocardial infarction. The combined usage of both ROCK activity and NT-proBNP might identify a subset of ACS patients at particularly high risk.
    International journal of cardiology 08/2012; · 7.08 Impact Factor
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    ABSTRACT: Rho kinases (ROCKs) are the best characterized effectors of the small G-protein RhoA, and play a role in enhanced vasoconstriction in animal models of congestive heart failure (CHF). This study examined if ROCK activity is increased in CHF and how it is associated with the outcome in CHF. Patients admitted with CHF (n =178), disease controls (n =31), and normal subjects (n =30) were studied. Baseline ROCK activity was measured by phosphorylation of themyosin-binding subunit in peripheral leucocytes. The patients were followed up for 14.4 ± 7.2 months (range 0.5-26 months) or until the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 ± 0.87) was significantly higher than that of the disease control (2.06 ± 0.38, P < 0.001) and normal control (1.57 ± 0.43, P < 0.001) groups. Similarly, protein levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were significantly higher than in disease controls and normal controls (all P < 0.05). Dyspnoea at rest (β =0.338, P < 0.001), low left ventricular ejection fraction (β = -0.277, P < 0.001), and high creatinine (β =0.202, P =0.006) were independent predictors of the baseline ROCK activity in CHF. Forty-five patients died within 2 years follow-up (25.3%). Combining ROCK activity and N-terminal pro brain natriuretic peptide (NT-proBNP) had an incremental value (log rank χ(2) =11.62) in predicting long-term mortality when compared with only NT-proBNP (log rank χ(2) =5.16, P < 0.05). ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification.
    European Journal of Heart Failure 05/2012; 14(9):965-73. · 5.25 Impact Factor
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    ABSTRACT: Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications. We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P<0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend<0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P<0.05 for all). Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity.
    Atherosclerosis 01/2012; 221(2):521-6. · 3.71 Impact Factor
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    ABSTRACT: Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. In seeking to elucidate the pathogenesis of BHD, we discovered a physical interaction between folliculin (FLCN), the protein product of the BHD gene, and p0071, an armadillo repeat containing protein that localizes to the cytoplasm and to adherens junctions. Adherens junctions are one of the three cell-cell junctions that are essential to the establishment and maintenance of the cellular architecture of all epithelial tissues. Surprisingly, we found that downregulation of FLCN leads to increased cell-cell adhesion in functional cell-based assays and disruption of cell polarity in a three-dimensional lumen-forming assay, both of which are phenocopied by downregulation of p0071. These data indicate that the FLCN-p0071 protein complex is a negative regulator of cell-cell adhesion. We also found that FLCN positively regulates RhoA activity and Rho-associated kinase activity, consistent with the only known function of p0071. Finally, to examine the role of Flcn loss on cell-cell adhesion in vivo, we utilized keratin-14 cre-recombinase (K14-cre) to inactivate Flcn in the mouse epidermis. The K14-Cre-Bhd(flox/flox) mice have striking delays in eyelid opening, wavy fur, hair loss, and epidermal hyperplasia with increased levels of mammalian target of rapamycin complex 1 (mTORC1) activity. These data support a model in which dysregulation of the FLCN-p0071 interaction leads to alterations in cell adhesion, cell polarity, and RhoA signaling, with broad implications for the role of cell-cell adhesion molecules in the pathogenesis of human disease, including emphysema and renal cell carcinoma.
    PLoS ONE 01/2012; 7(11):e47842. · 3.73 Impact Factor

Publication Stats

9k Citations
1,172.64 Total Impact Points

Institutions

  • 2010–2013
    • Tokyo Medical and Dental University
      • Department of Molecular Endocrinology and Metabolism
      Edo, Tōkyō, Japan
  • 2012
    • Chang Gung Memorial Hospital
      T’ai-pei, Taipei, Taiwan
    • Spaulding Rehabilitation Hospital
      • Department of Physical Medicine and Rehabilitation
      Boston, MA, United States
  • 2010–2012
    • The Chinese University of Hong Kong
      • Prince of Wales Hospital
      Hong Kong, Hong Kong
  • 2002–2012
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 1999–2012
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      Boston, MA, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2007–2010
    • Hiroshima University
      • • Department of Cardiovascular Medicine
      • • Department of Cardiovascular Physiology and Medicine
      Hiroshima-shi, Hiroshima-ken, Japan
    • National Cheng Kung University
      • Department of Internal Medicine
      Tainan, Taiwan, Taiwan
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2009
    • Beth Israel Deaconess Medical Center
      • CardioVascular Institute
      Boston, MA, United States
  • 2005–2009
    • Massachusetts General Hospital
      • Department of Neurology
      Boston, Massachusetts, United States
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China
    • St. Josef-Hospital
      Bonn, North Rhine-Westphalia, Germany
  • 2008
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2004–2008
    • Columbia University
      • Division of Pediatric Cardiology
      New York City, New York, United States
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
    • Humboldt-Universität zu Berlin
      • Microbiology, Molecular Biology, and Biochemistry Section
      Berlín, Berlin, Germany
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2006
    • Imperial College London
      • Faculty of Medicine
      Londinium, England, United Kingdom
    • Rutgers New Jersey Medical School
      • Department of Cell Biology and Molecular Medicine (NJ Medical School)
      Newark, NJ, United States
  • 2003
    • University of Texas Southwestern Medical Center
      • Department of Biochemistry
      Dallas, TX, United States
    • Medical University of South Carolina
      • Department of Biochemistry and Molecular Biology (College of Medicine)
      Charleston, South Carolina, United States
  • 2000
    • Johannes Gutenberg-Universität Mainz
      • III. Department of Medicine
      Mainz, Rhineland-Palatinate, Germany