Suthat Fucharoen

Mahidol University, Krung Thep, Bangkok, Thailand

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Publications (182)516.46 Total impact

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    ABSTRACT: Dengue is the most significant arthropod borne viral disease worldwide, and infection with the dengue virus causes a wide range of symptoms in humans, including bone marrow suppression. While the target cells of the virus remain poorly characterized, cells of the myeloid lineage have been shown to be important mediators of the disease. This study sought to determine whether erythroid precursor cells were susceptible to dengue virus infection, and whether erythroid cells from thalassemia trait carriers showed any protection against infection. Infection with a laboratory adapted high passage DENV-2 resulted in high levels of infection during certain stages of differentiation, and cells derived from thalassemia trait carriers showed significantly reduced susceptibility to dengue virus infection. Infection with low passage isolates resulted in only scattered cells showing evidence of infection, but high bystander apoptosis that was reduced by both a caspase 8 inhibitor and anti-tumor necrosis factor 1 receptor antibodies.
    Virology. 12/2014; 471.
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    ABSTRACT: Serum EPO concentration is related primarily to the rate of erythrocyte production and, under the stimulation of hypoxia, increases exponentially as hemoglobin (Hb) decreased. The level of EPO was determined in 141 subjects including 43 normal, 44 thalassemic patients and 54 thalassemic trait subjects. The EPO level was significantly higher in the thalassemic patients (54.8mU/ml in HbH disease [α thal1/α thal2;], 78.1mU/ml in HbH with Hb CS [α thal 1/CS]; 95.6mU/ml in β-thal/HbE splenectomized [BE(S)]; and 114.8mU/ml in β-thal/HbE non-splenectomized [BE(NS)]as compared with 12.0mU/ml in normal subjects. No significant differences were detected in thalassemic trait subjects. In addition, the levels of EPO in thalassemic patients is correlated significantly with the number of reticulocytes and the reticulocyte fractions especially the fraction of immature reticulocytes. Interestingly, the highest level of EPO/% retic ratio as indicated for EPO non-responder was detected in BE(NS) patients. However, the impaired reticulocytes maturation was found to be related significantly with the levels of TNF-α,IFN-γ,IL-10, and VEGF. Since, TNF-α, IFN-γ, IL-10 and VEGF are reported as the cytokines with erythropoietic inhibitory mediators, the variation of these cytokines in thalassemic environments may be associated to the anemic crisis in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.
    Blood Cells Molecules and Diseases 11/2014; · 2.26 Impact Factor
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    ABSTRACT: α(0)-Thalassemia occurs from a deletion of 2 linked α-globin genes and interaction of these defective genes leads to hemoglobin (Hb) Bart's hydrops fetalis, the most severe and lethal thalassemia syndrome. Identification of α(0)-thalassemia carriers is thus essential for the prevention and control program. An immunochromatographic (IC) strip test was developed for rapid screening of α(0)-thalassemia by testing for Hb Bart's in the blood samples using a specific monoclonal antibody against Hb Bart's. To evaluate its sensitivity and specificity, the IC strip test was assessed in a cohort with various thalassemia genotypes from 4 different laboratories in Thailand and Australia. The result showed 97% sensitivity in α-thalassemia carriers with 2 α-globin genes deletion and Hb H disease. This is, in particular, the useful rapid screening test for regions where β-thalassemia and homozygous Hb E are also common. Similar hematologic and Hb data make it impossible to address the concomitant inheritance of α(0)-thalassemia in these samples without polymerase chain reaction (PCR)-based techniques, leading to misdiagnosis of the risk of having Hb Bart's hydrops fetalis. However, α-globin genotyping should be carried out in samples with positive IC strip as positive reactivity was also observed in homozygous α(+)-thalassemia carriers who have 2 trans α-globin gene deletions. These results indicate that in combination with red blood cell indices, the IC strip test could rule out mass populations for further α(0)-thalassemia detection by PCR-based analysis. The Alpha Thal IC strip also has the potential to replace testing for Hb H inclusion bodies, as it appears to be more sensitive, specific, and less labor intensive. Copyright © 2014 Elsevier Inc. All rights reserved.
    Translational Research. 11/2014;
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    ABSTRACT: Pulmonary arterial hypertension is a life-threatening complication in thalassemia characterized by elevated pulmonary arterial pressure. Increased platelet activation is associated with this complication; however, its role remains unclear. Platelet activation in splenectomized β-thalassemia/hemoglobin E (Hb E) patients was measured using flow cytometric determination of P-selectin and activated glycoprotein (aGP) IIb/IIIa expression, and platelet-leukocyte aggregates (platelet-neutrophil, platelet-monocyte and platelet-lymphocyte aggregates). Tricuspid regurgitant velocity (TRV) was measured and used as an indicator of pulmonary arterial pressure. Plasma hemoglobin served as markers of hemolysis. Fifteen of 27 patients had elevated TRV (>2.5m/s). Platelet expression of P-selectin and aGPIIb/IIIa, and platelet-leukocyte aggregates were higher in thalassemia patients with elevated TRV than healthy control. Platelet-neutrophil aggregates increased in thalassemia patients with elevated TRV compared to patients with normal TRV. The increase in P-selectin and aGPIIb/IIIa expression induced by adenosine diphosphate (ADP) was higher in patients with elevated TRV than those with normal TRV. Platelet P-selectin expression and platelet-neutrophil aggregates correlated positively with TRV. Plasma hemoglobin levels in patients with elevated TRV were higher than those of the control subjects, and correlated with TRV. Thalassemia patients with elevated TRV have a further increase in platelet activation that correlates with hemolysis. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 10/2014; · 3.13 Impact Factor
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    ABSTRACT: Infection is one of the most common causes of death in β-thalassemia patients. This may be due in part to an underlying immunological abnormality. During the past decade, a subset of CD3+ T cells that express both CD4+CD8+ (DP) T-cells were discovered and have been described in several pathological conditions. However, phenotypic characterization of this unique T-lymphocyte subset in patients with β-thalassemia has not yet been investigated.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 09/2014; 32(3):261-269. · 0.79 Impact Factor
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    ABSTRACT: To evaluate efficacy and toxicity of a novel orally active bidentate iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in mice under normal and iron overload conditions.
    Asian Pacific Journal of Tropical Medicine 09/2014; 7S1:S155-61. · 0.50 Impact Factor
  • Journal of Cardiovascular Magnetic Resonance 08/2014; · 4.44 Impact Factor
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    ABSTRACT: To evaluate the iron-chelating properties and free-radical scavenging activities of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) treatment in chronic iron-loaded β-thalassemic (BKO) mice.
    Asian Pacific Journal of Tropical Biomedicine 08/2014; 4(8):663-8.
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    ABSTRACT: The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice ((mu)β(th-3/+), BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 06/2014; · 1.43 Impact Factor
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    ABSTRACT: Immunotherapy has been developed to treat cancers. There are many signaling pathways involved in cytokine induced apoptosis of many cancers but their role remains unclear in some cancers such as leukemia.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 06/2014; 32(2):133-139. · 0.79 Impact Factor
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    ABSTRACT: Expression of fetal γ-globin in adulthood ameliorates symptoms of β-hemoglobinopathies by compensating for the mutant β-globin. Reactivation of the silenced γ-globin gene is therefore of substantial clinical interest. To study the regulation of γ-globin expression, we created the GG mice, which carry an intact 183-kb human β-globin locus modified to express enhanced green fluorescent protein (eGFP) from the Gγ-globin promoter. GG embryos express eGFP first in the yolk sac blood islands and then in the aorta-gonad mesonephros and the fetal liver, the sites of normal embryonic hematopoiesis. eGFP expression in erythroid cells peaks at E9.5 and then is rapidly silenced (>95%) and maintained at low levels into adulthood, demonstrating appropriate developmental regulation of the human β-globin locus. In vitro knockdown of the epigenetic regulator DNA methyltransferase-1 in GG primary erythroid cells increases the proportion of eGFP(+) cells in culture from 41.9 to 74.1%. Furthermore, eGFP fluorescence is induced >3-fold after treatment of erythroid precursors with epigenetic drugs known to induce γ-globin expression, demonstrating the suitability of the Gγ-globin eGFP reporter for evaluation of γ-globin inducers. The GG mouse model is therefore a valuable model system for genetic and pharmacologic studies of the regulation of the β-globin locus and for discovery of novel therapies for the β-hemoglobinopathies.-McColl, B., Kao, B. R., Lourthai, P. Chan, K., Wardan, H., Roosjen, M., Delagneau, O. Gearing, L. J., Blewitt, M. E, Svasti, S., Fucharoen, S., Vadolas, J. An in vivo model for analysis of developmental erythropoiesis and globin gene regulation.
    The FASEB Journal 01/2014; · 5.70 Impact Factor
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    ABSTRACT: The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180 mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice (muβth-3/+, BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators.
    Experimental and Toxicologic Pathology. 01/2014;
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    ABSTRACT: BACKGROUND:The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.METHODS:Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy.RESULTS:From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (+/-SD) 23.7+/-0.93ms at baseline (13days after death and formalin fixation) to 18.5+/-1.41ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe]=5081 *(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3+/-25.8ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12months. In the remaining hearts stored for <10weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001).CONCLUSION:Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.
    Journal of Cardiovascular Magnetic Resonance 01/2014; 16(1):62. · 4.44 Impact Factor
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    ABSTRACT: Crohn's disease is an inflammatory bowel disease. Because of strong heritability, it is possible to deploy the pattern of DNA variations, such as single nucleotide polymorphisms (SNPs), to accurately predict the state of this disease. However, there are many possible SNP subsets, which make finding a best set of SNPs to achieve the highest prediction accuracy impossible in one patient's lifetime. In this paper, a new technique is proposed that relies on chromosomes of various lengths with significant order feature selection, a new cross-over approach, and new mutation operations. Our method can find a chromosome of appropriate length with useful features. The Crohn's disease data that were gathered from case–control association studies were used to demonstrate the effectiveness of our proposed algorithm. In terms of the prediction accuracy, the proposed SNP prediction framework outperformed previously proposed techniques, including the optimum random forest (ORF), the univariate marginal distribution algorithm and support vector machine (USVM), the complimentary greedy search-based prediction algorithm (CGSP), the combinatorial search-based prediction algorithm (CSP), and discretized network flow (DNF). The performance of our framework, when tested against this real data set with a 5-fold cross-validation, was 90.4% accuracy with 87.5% sensitivity and 92.2% specificity.
    Computers in biology and medicine 01/2014; 44:57–65. · 1.27 Impact Factor
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    ABSTRACT: Nitric oxide (NO), a small gas molecule, has long been known to be a potent inhibitor of platelet function but the physiological and pathological implications of platelet inhibition by NO have not been well clarified. We recently showed that the addition of nitrite to platelet-rich plasma in the presence of erythrocytes could inhibit platelet aggregation and this inhibitory effect of nitrite + erythrocytes was enhanced by deoxygenation of erythrocytes as measured by P-selectin expression and cGMP production. In order to study the nitrite effect on platelets at different oxygen levels, we used the flow cytometric assays to detect platelet membrane surface markers upon activation. The P-selectin and activated gpIIb/IIIa expression on platelet membranes in response to ADP, collagen and thrombin stimulation was measured at various hematocrit and oxygen levels. Nitrite (0.1 to 1.0 μM) significantly decreased the percentage of these surface markers on the platelet membrane at the hematocrit values above 23% and oxygen levels lower than 49 mmHg. The inhibitory effect of nitrite was augmented by increasing hematocrit values and decreasing oxygen saturation. C-PTIO (an NO scavenger) prevented the platelet inhibition by nitrite + erythrocytes whereas the inhibitors of NO synthase and xanthine oxidoreductase had no effect. These results support the proposal that circulating nitrite decreases platelet reactivity in the presence of partially deoxygenated erythrocytes through its reduction to NO, which may also explain certain differences between arterial and venous thrombosis and support directly the role of deoxyhemoglobin in this process. We believe that our flow cytometric assays offer a possibility to identify the individual molecular process involved in these effects.
    PLoS ONE 01/2014; 9(3):e92435. · 3.53 Impact Factor
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    ABSTRACT: HbH and HbH-constant spring (HbH-CS) are the most common forms of α-thalassemia detected in the Thai population. The accumulation of excess β globin chains in these diseases results in increased red cell hemolysis, and patients with HbH-CS normally have a more severe clinical presentation than patients with HbH disease. This study aimed to detect alterations in the expression of plasma proteins of HbH and HbH-CS patients as compared to normal plasma. Platelet poor plasma was separated from HbH and HbH-CS and normal subjects and differential plasma proteins were detected using two-dimensional gel electrophoresis and identified using LC/MS/MS. A total of 14 differentially expressed proteins were detected of which 5 proteins were upregulated and 9 were downregulated. Most of the differentially expressed proteins are liver secreted proteins involved in hemolysis, oxidative stress response, and hemoglobin degradation. Seven proteins were found to be differentially expressed between HbH and HbH-CS. Levels of haptoglobin, a hemoglobin scavenging protein, were significantly increased in HbH patients as compared to HbH-CS patients. The identification of differentially expressed proteins may lead to a better understanding of the biological events underlying the clinical presentation of HbH and HbH-CS patients and can have application as hemolytic markers or severity predictors.
    Disease markers. 01/2014; 2014:340214.
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    ABSTRACT: A major clinical feature of patients with thalassemia is growth retardation due to anemia, therefore, the hematological parameters, weanling weight and post-weanling weight of pups obtained from vitrifiedwarmed embryo transfers were studied for the first time in this report. Two-cell embryos of four transgenic (TG) thalassemic mouse lines (BKO, 654, E2, and E4) were produced by breeding four lines of TG thalassemic males to wild-type (WT) females (C57BL/6J) and were cryopreserved by vitrification in straws using 35% ethylene glycol. After transfer of vitrified-warmed embryos, hematological parameters, spleen index, weanling and post-weanling weight were determined in TG and WT viable pups. In the BKO and 654 mice significantly abnormal hematological parameters and spleen index were observed compared to WT, E2 and E4 mice. The weanling and post-weanling weights of BKO and 654 pups were significantly less than that of the age-matched WT pups. However, no significant differences in weanling and post-weanling weight were found between WT and E2-TG or E4-TG pups. In conclusion, the four transgenic mice lines produced from cryopreserved embryo transfer retain the phenotype of the natural breeding mice indicating that these banked embryos are appropriate for thalassemia model productions.
    Acta Biologica Hungarica 12/2013; 64(4):453-61. · 0.50 Impact Factor
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    ABSTRACT: β-thalassaemia is a hereditary anaemia resulting from the absence or reduction in β-globin chain production. Heart complications related to iron overload are the most serious cause of death in these patients. In this report cardiac pathology of β-thalassaemic mice was evaluated by light and electron microscopy. The study was carried out in thalassaemic mice carrying human β-thalassaemia mutation, IVSII-654 (654), transgenic mice carrying human β(E) -globin transgene insertion (E4), thalassaemic mice with human β(E) -globin transgene insertion (654/E4) and homozygous thalassaemic mice rescued by the human β(E) -globin transgene (R), which is generated by cross-breeding between the 654 and E4 mice. Histology showed iron deposition in cardiac myocytes of 654 and R mice, but the ultrastructural damage was observed only in the R mice when compared with the wild type, 654, E4 and 654/E4 mice. Histopathological changes in the cardiomyocytes of the R mice included mitochondrial swelling, loss of myofilaments and the presence of lipofuscin, related to the increased level of tissue iron content. The progressive ultrastructural pathology in R mice cardiomyocytes is consistent with the ultrastructural pathology previously studied in patients with thalassaemia. Thus, this R thalassaemic mouse model is suitable for in vivo pathophysiological study of thalassaemic heart.
    International Journal of Experimental Pathology 10/2013; 94(5):336-42. · 2.04 Impact Factor
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    ABSTRACT: Myocardial siderosis is known as the major cause of death in thalassemia major (TM) patients since it can lead to iron overload cardiomyopathy. Although this condition can be prevented if timely effective intensive chelation is given to patients, the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition. Various direct and indirect methods of iron assessment, including serum ferritin level, echocardiogram, non-transferrin-bound iron, cardiac magnetic resonance T2*, heart rate variability, and liver biopsy and myocardial biopsy, have been proposed for early detection of cardiac iron overload in TM patients. However, controversial evidence and limitations of their use in clinical practice exist. In this review article, all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented. Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients, these two methods are also presented and discussed. The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.
    World Journal of Cardiology (WJC) 08/2013; 5(8):270-279. · 2.06 Impact Factor

Publication Stats

2k Citations
516.46 Total Impact Points

Institutions

  • 1981–2014
    • Mahidol University
      • • Department of Pharmacology
      • • Institute of Molecular Biosciences
      • • Department of Clinical Microscopy
      • • Faculty of Graduate Studies
      • • Faculty of Medicine Siriraj Hospital
      Krung Thep, Bangkok, Thailand
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2012–2013
    • Ramathibodi Hospital
      Krung Thep, Bangkok, Thailand
  • 2006–2013
    • Chiang Mai University
      • • Department of Physiology
      • • Faculty of Medicine
      • • Department of Biochemistry
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
    • Chulalongkorn University
      • • Department of Mathematics and Computer Science
      • • Department of Pharmacology
      Krung Thep, Bangkok, Thailand
    • Srinakharinwirot University
      • Department of Biochemistry
      Bangkok, Bangkok, Thailand
  • 2010
    • Prince of Songkla University
      • Faculty of Medicine
      Songkhla, Changwat Songkhla, Thailand
    • Boston University
      • Department of Medicine
      Boston, MA, United States
  • 2002–2009
    • University of North Carolina at Chapel Hill
      • • Department of Pharmacology
      • • Lineberger Comprehensive Cancer Center
      Chapel Hill, NC, United States
  • 2008
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem District, Israel
    • Phramongkutklao Hostpital
      Krung Thep, Bangkok, Thailand
  • 2003–2006
    • Murdoch Childrens Research Institute
      • • Research Group for Cell & Gene Therapy
      • • Research Group for Heart Research
      Melbourne, Victoria, Australia
  • 2005
    • University of Melbourne
      • Department of Paediatrics
      Melbourne, Victoria, Australia
  • 2002–2005
    • Chulabhorn Research Institute
      • Laboratory of Biochemistry
      Krung Thep, Bangkok, Thailand