Research Topics
Genomes and Genes | Hector WongSummaryAffiliation: Cincinnati Children's Hospital Medical Center Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Genome-wide expression profiling in pediatric septic shockHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Hospital Research Foundation, Cincinnati, Ohio, USA
Pediatr Res 73:564-9. 2013..The studies have progressed from an initial discovery-oriented and exploratory phase to a new phase in which the data are being translated and applied to address several areas of clinical need...
Clinical review: sepsis and septic shock--the potential of gene arraysHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
Crit Care 16:204. 2012..The challenges moving forward include robust validation studies, standardization of technical approaches, standardization and further development of analytical algorithms, and large-scale collaborations...
Genetics and genomics in pediatric septic shockHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Crit Care Med 40:1618-26. 2012..This review will highlight studies in pediatric sepsis with a focus on gene association studies and genome-wide expression profiling...
Finding new therapies for sepsis: the need for patient stratification and the use of genetic biomarkersMichael J Hobson
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
Crit Care 15:1009. 2011..The efficacy of future therapies may be better studied under an effective system of patient stratification. Gene expression biomarkers offer a mechanism by which patients may be appropriately stratified in such clinical trials...
Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarrayRajit K Basu
Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45223, USA
Crit Care 15:R273. 2011..The objective of our study was to determine whether microarray data from children with septic shock could be used to derive a panel of candidate biomarkers for predicting SSAKI...
CpG DNA modulates interleukin 1beta-induced interleukin-8 expression in human bronchial epithelial (16HBE14o-) cellsN William Parilla
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
Respir Res 7:84. 2006..We sought to investigate the role of CpG oligodeoxynucleotides (ODN) on a human bronchial epithelial cells...
Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4Derek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati Children s Research Foundation, Cincinnati, OH, USA
Respir Res 10:31. 2009..Heat shock proteins (HSPs) are generally regarded as intracellular proteins acting as molecular chaperones; however, HSP72 can also be released from cells, and the implications of this release are not fully understood...
Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shockHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
Am J Respir Crit Care Med 178:276-82. 2008..Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy...
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcomeHector R Wong
Cincinnati Children s Hospital Medical Center and Cincinnati Children s Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Physiol Genomics 30:146-55. 2007..The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock...
Identification of pediatric septic shock subclasses based on genome-wide expression profilingHector R Wong
Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
BMC Med 7:34. 2009..Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling...
Divergence of canonical danger signals: the genome-level expression patterns of human mononuclear cells subjected to heat shock or lipopolysaccharideHector R Wong
Department of Pediatrics, University of Cincinnati College of Medicine, Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Cincinnati, Ohio, USA
BMC Immunol 9:24. 2008..Herein we have directly compared the genome-level expression patterns (microarray) of a human PBMC model (THP-1 cells) subjected to one of two canonical danger signals, heat shock or lipopolysaccharide (LPS)...
Leukocyte subset-derived genomewide expression profiles in pediatric septic shockHector R Wong
Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Pediatr Crit Care Med 11:349-55. 2010..To directly assess whether genomewide expression profiles derived from leukocyte subsets are comparable to that of whole blood as measured by enrichment for genes corresponding to metabolic and signaling pathways...
Toward a clinically feasible gene expression-based subclassification strategy for septic shock: proof of conceptHector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Crit Care Med 38:1955-61. 2010..To develop a clinically feasible stratification strategy for pediatric septic shock, using gene expression mosaics and a 100-gene signature representing the first 24 hrs of admission to the pediatric intensive care unit...
Validation of a gene expression-based subclassification strategy for pediatric septic shockHector R Wong
Department of Pediatrics, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Crit Care Med 39:2511-7. 2011..Here we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort...
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrumHector R Wong
Department of Pediatrics, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Crit Care Med 37:1558-66. 2009....
Contribution of MKP-1 regulation of p38 to endotoxin toleranceMarianne Nimah
Division of Critical Care Medicine, Cincinnati Children s Hospital Research Foundation, University of Cincinnati Medical School, Cincinnati, Ohio 45229 3039, USA
Shock 23:80-7. 2005..wild type) mice (24% vs. 72% reductions, respectively). These data demonstrate that the dual specific phosphatase MKP-1 is an important mediator of endotoxin tolerance via p38 regulation...
Heat shock inhibition of lipopolysaccharide-mediated tumor necrosis factor expression is associated with nuclear induction of MKP-1 and inhibition of mitogen-activated protein kinase activationLauren Sanlorenzo
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, OH, USA
Crit Care Med 32:2284-92. 2004..Modulation of phosphatase activity may be a potential strategy for attenuating acute inflammatory responses...
Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in ratsRajesh Aneja
Department of Pediatrics, Division of Critical Care Medicine OSB5, Cincinnati Children s Hospital Medical Center and College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Mol Med 10:55-62. 2004..The results of this study suggest that EGCG is beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the NF-kappaB and AP-1 pathway...
Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damageBasilia Zingarelli
Children s Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio 45229, USA
FASEB J 16:327-42. 2002..Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction...
Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodentsMaeve Sheehan
Children's Hospital Medical Center, Division of Critical Care Medicine, Cincinnati, Ohio 45229, USA
Mol Pharmacol 61:953-63. 2002..We conclude that parthenolide exerts beneficial effects during endotoxic shock through inhibition of NF-kappaB...
Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitisPatricia A Abboud
Cincinnati Children s Hospital Medical Center, Division of Critical Care Medicine, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
Eur J Pharmacol 579:411-7. 2008..Our data demonstrate that EGCG may be beneficial in colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of NF-kappaB and AP-1...
Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shockJennifer M Kaplan
Cincinnati Children s Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 2005, Cincinnati, OH 45229 3039, USA
Intensive Care Med 36:123-30. 2010..Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma activity, adiponectin and resistin...
Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-CJames P Bridges
Division of Pulmonary Biology, Cincinnati Children s Hospital Medical Center, The University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
J Cell Biol 172:395-407. 2006..The wide variability in the age of onset of ILD in patients with SFTPC mutations may be related to environmental insults that ultimately overwhelm the homeostatic cytoprotective response...
Theaflavin, a black tea extract, is a novel anti-inflammatory compoundRajesh Aneja
Division of Critical Care Medicine, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, and Children's Hospital Research Foundation, Cincinnati, OH, USA
Crit Care Med 32:2097-103. 2004..CONCLUSIONS: We conclude that theaflavin is a potent inhibitor of interleukin-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IkappaB kinase activation and activator protein-1 pathway...
Role of heat shock protein 70 in hepatic ischemia-reperfusion injury in miceSatoshi Kuboki
The Laboratory of Trauma, Sepsis and Inflammation Research, University of Cincinnati, Department of Surgery, 231 Albert Sabin Way, Cincinnati, OH 45267 0558, USA
Am J Physiol Gastrointest Liver Physiol 292:G1141-9. 2007..Targeted induction of HSP70 may represent a potential therapeutic option for postischemic liver injury...
Heat shock inhibits activation of NF-kappaB in the absence of heat shock factor-1Vivek Malhotra
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA
Biochem Biophys Res Commun 291:453-7. 2002..These data demonstrate that heat shock inhibits activation of the NF-kappaB/IkappaBalpha pathway and NF-kappaB-dependent gene expression in the absence of an intact heat shock response...
The role of endogenously produced extracellular hsp72 in mononuclear cell reprogrammingPatricia A Abboud
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Shock 30:285-92. 2008..These data demonstrate that endogenously produced and released extracellular Hsp72 has the ability to reprogram the in vitro response to endotoxin in cultured human mononuclear cells...
Activation of hepatocytes by extracellular heat shock protein 72Elizabeth Galloway
The Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, OH 45267 0558, USA
Am J Physiol Cell Physiol 295:C514-20. 2008..The fact that eHSP-72 did not increase TNF-alpha or IL-6 production may be indicative of a highly regulated signaling pathway downstream from TLR...
Interactions between the heat shock response and the nuclear factor-kappa B signaling pathwayVivek Malhotra
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA
Crit Care Med 30:S89-95. 2002..Further understanding of how these two fundamental cellular responses interact at the molecular level holds the potential to elucidate some of the molecular interactions that occur during disease states common to critical care medicine...
Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-kappaB, heat shock factor 1, and AktBasilia Zingarelli
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, The University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
Shock 28:554-63. 2007..In contrast, GW-9662 did not affect the beneficial effects afforded by 15d-PGJ2. Thus, our data suggest that treatment with these chemically unrelated PPAR-gamma ligands results in diverse anti-inflammatory mechanisms...
Induction of endotoxin tolerance enhances bacterial clearance and survival in murine polymicrobial sepsisDerek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
Shock 30:267-73. 2008..Contrary to our original hypothesis, we conclude that endotoxin tolerance significantly attenuates the host inflammatory response, augments bacterial clearance, and improves survival in this murine model of polymicrobial sepsis...
The green tea polyphenol epigallocatechin-3-gallate improves systemic hemodynamics and survival in rodent models of polymicrobial sepsisDerek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
Shock 28:353-9. 2007..Epigallocatechin-3-gallate may therefore represent a potential nutritional supplement or pharmacologic agent in patients with sepsis...
Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shockDerek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
Crit Care Med 36:1297-303. 2008..To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury in critically ill children with septic shock...
Therapeutic application of intrapericardial tissue plasminogen activator in a 4-month-old child with complex fibropurulent pericarditisMichael T Bigham
Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
Pediatr Crit Care Med 9:e1-4. 2008..To describe a young child with complex fibropurulent pericarditis who was successfully treated with intrapericardial recombinant tissue plasminogen activator...
Age-related decrease in proteasome expression contributes to defective nuclear factor-kappaB activation during hepatic ischemia/reperfusionNadine Huber
Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, OH 45267 0558, USA
Hepatology 49:1718-28. 2009..It appears that decreased PSMD4 expression prevents recruitment of phosphorylated and ubiquitinylated IkappaB alpha to the proteasome, resulting in a defect in NF-kappaB activation...
Lung injury after hemorrhage is age dependent: role of peroxisome proliferator-activated receptor gammaBasilia Zingarelli
Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
Crit Care Med 37:1978-87. 2009..We investigated whether the pathophysiologic characteristics of hemorrhage-induced lung injury may be age dependent and may be regulated by the peroxisome proliferator-activated receptor gamma (PPARgamma)...
Novel pharmacologic approaches to the management of sepsis: targeting the host inflammatory responseDerek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
Recent Pat Inflamm Allergy Drug Discov 3:96-112. 2009..We will also reference some of the patents recently filed that pertain to the host innate immune response and sepsis...
Admission chemokine (C-C motif) ligand 4 levels predict survival in pediatric septic shockJeffrey E Nowak
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
Pediatr Crit Care Med 11:213-6. 2010..The objective of this study was to test the usefulness of chemokine (C-C motif) ligand 4 as an outcome biomarker for mortality in pediatric septic shock...
Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1Basilia Zingarelli
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Am J Physiol Heart Circ Physiol 286:H1408-15. 2004..The data indicate that PARP-1 may exert a pathological role in reperfusion injury by functioning as an enhancing factor of AP-1 activation and as a repressing factor of HSF-1 activation and HSP70 expression...
A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB kinase activation and IL-8 gene expression in respiratory epitheliumPhilip C Chen
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, OH 45244, USA
Inflammation 26:233-41. 2002..We conclude that EGCG is a potent inhibitor of IL-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IkappaB kinase activation...
Temporal and mechanistic effects of heat shock on LPS-mediated degradation of IkappaBalpha in macrophagesBruce J Grossman
Division of Critical Care Medicine, Children s Hospital Medical Center, and Children s Hospital Research Foundation, Cincinnati, OH 45229 3039, USA
Inflammation 26:129-37. 2002..The mechanism by which heat shock inhibits degradation of IkappaBalpha involves dual modulation of IKK and intracellular phosphatase activity...
Heat shock-mediated regulation of MKP-1Hector R Wong
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA
Am J Physiol Cell Physiol 289:C1152-8. 2005..These data demonstrate another potential mechanism by which heat shock can modulate inflammation-related signal transduction...
Sesquiterpene lactone parthenolide, an inhibitor of IkappaB kinase complex and nuclear factor-kappaB, exerts beneficial effects in myocardial reperfusion injuryBasilia Zingarelli
Children's Hospital Medical Center, Division of Critical Care Medicine, Cincinnati, Ohio 45229, USA
Shock 17:127-34. 2002..The results of this study suggest that parthenolide may be beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the IKK/NF-kappaB pathway...
Molecular genetics in the pediatric intensive care unitThomas P Shanley
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Crit Care Clin 19:577-94. 2003..Ultimately, the generation of more comprehensive and fundamental knowledge can lead to the design of more effective and specific therapeutic strategies...
Parthenolide improves systemic hemodynamics and decreases tissue leukosequestration in rats with polymicrobial sepsisMaeve Sheehan
Cincinnati Children's Hospital, OH, USA
Crit Care Med 31:2263-70. 2003..These beneficial effects of parthenolide were associated with reduction of NF-kappaB activity in the lung. CONCLUSIONS: Our data suggest that pharmacologic inhibition of NF-kappaB may represent a potential therapeutic approach in sepsis...
Hyperoxia prolongs tumor necrosis factor-alpha-mediated activation of NF-kappaB: role of IkappaB kinaseHector R Wong
Division of Critical Care Medicine, Children s Hospital Medical Center and Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
Shock 17:274-9. 2002..The mechanism of this effect involves, in part, prolonged degradation of IkappaB alpha resulting from prolonged activation of IKK...
Hsp72 induces inflammation and regulates cytokine production in airway epithelium through a TLR4- and NF-kappaB-dependent mechanismMargaret A Chase
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
J Immunol 179:6318-24. 2007..Taken together, these data suggest that Hsp72 is released and biologically active in the BALF and can regulate airway epithelial cell cytokine expression in a TLR4 and NF-kappaB-dependent mechanism...
Phosphatase inhibition leads to activation of IkappaB kinase in murine macrophagesBruce J Grossman
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and The Children's Hospital Research Foundation, Division of Critical Care Medicine-OSB-5, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
Biochem Biophys Res Commun 297:1264-9. 2002..Inhibition of intracellular phosphatase activity with calyculin-A is not sufficient to induce NF-kappaB-dependent gene expression, demonstrating the complexity of NF-kappaB regulation in immune cells...
Short-term modulation of interleukin-1beta signaling by hyperoxia: uncoupling of IkappaB kinase activation and NF-kappaB-dependent gene expressionKelli Odoms
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
Am J Physiol Lung Cell Mol Physiol 286:L554-62. 2004..This activation, however, is not coupled to increased expression of NF-kappaB-dependent genes, and the mechanism of this decoupling is not related to decreased phosphorylation of p65...
The A2A receptor mediates an endogenous regulatory pathway of cytokine expression in THP-1 cellsKhaled Bshesh
Division of Critical Care Medicine, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
J Leukoc Biol 72:1027-36. 2002..Thus, following immune activation with LPS, endogenous adenosine mediates a negative feedback pathway to modulate cytokine expression in THP-1 cells...
Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domainDerek S Wheeler
Division of Critical Care Medicine-OSB5, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45244, USA
Biochem Biophys Res Commun 301:54-9. 2003....
Nuclear factor-kappaB as a therapeutic target in critical care medicineBasilia Zingarelli
Children s Hospital Medical Center, Division of Critical Care Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
Crit Care Med 31:S105-11. 2003..The purpose of our review is to describe these novel therapeutic approaches and their potential efficacy...
An update and review of acute kidney injury in pediatricsRajit K Basu
Division of Critical Care, Department of Pediatrics, Cincinnati Children s Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA
Pediatr Crit Care Med 12:339-47. 2011..To inform the pediatric intensivist of recent advancements in acute kidney injury diagnosis and management...
Age-dependent responses to hepatic ischemia/reperfusion injuryTomohisa Okaya
The Laboratory of Trauma, Sepsis, and Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA
Shock 24:421-7. 2005..These data suggest that there are multiple alterations at the cellular and molecular levels that contribute to enhanced postischemic liver injury in mature adult mice...
Mechanisms and regulation of the gene-expression response to sepsisTimothy T Cornell
Division of Critical Care Medicine, C S Mott Children s Hospital, University of Michigan, Ann Arbor, MI, USA
Pediatrics 125:1248-58. 2010..We anticipate that emerging data from genetic, genomic, and other translation studies in pediatric sepsis will advance our biological understanding of this response and undoubtedly identify targets for newer therapies...
Extracellular hsp70 levels in children with septic shockDerek S Wheeler
Department of Pediatrics, University of Cincinnati College of Medicine and Children's Hospital Research Foundation, Cincinnati, OH, USA
Pediatr Crit Care Med 6:308-11. 2005..Given the newly described cell signaling properties of hsp70, these data suggest that extracellular hsp70 may play a role in the host response during septic shock...
Pathophysiology and treatment of septic shock in neonatesJames L Wynn
Division of Neonatal Perinatal Medicine, Department of Pediatrics, Duke University, 2424 Hock Plaza, Suite 504, DUMC Box 2739, Durham, NC 27710, USA
Clin Perinatol 37:439-79. 2010..Although at present antimicrobial therapy and supportive care remain the foundation of treatment, in the future immunomodulatory agents are likely to improve outcomes for this vulnerable population...
Ablation of the heat shock factor-1 increases susceptibility to hyperoxia-mediated cellular injuryVivek Malhotra
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati Ohio 45229 3039, USA
Exp Lung Res 28:609-22. 2002..These data demonstrate that HSF-1 plays an important role in conferring resistance to hyperoxia in vitro...
Admission angiopoietin levels in children with septic shockJohn S Giuliano
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Shock 28:650-654. 2007..Given the contrasting effects of angpt-2 and angpt-1 on the vascular endothelium, these two factors may play an important role in the pathophysiology of septic shock in children, and further studies are warranted...
PP2A regulates upstream members of the c-jun N-terminal kinase mitogen-activated protein kinase signaling pathwayBin Zhao
Division of Pediatric Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Shock 29:181-8. 2008..Furthermore, PP2A-A/alpha seems to serve as a structural protein to foster protein-protein interactions affording specificity of the regulation among members of this MAP kinase pathway...
Heat shock response and acute lung injuryDerek S Wheeler
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Kindervelt Laboratory for Critical Care Medicine Research, Childrens Hospital Research Foundation, Cincinnati, OH 45229, USA
Free Radic Biol Med 42:1-14. 2007....
Heat shock inhibits tnf-induced ICAM-1 expression in human endothelial cells via I kappa kinase inhibitionGary Kohn
Division of Pulmonary Medicine, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
Shock 17:91-7. 2002..We conclude that heat shock decreases endothelial cell ICAM-1 expression via inhibition of IKK activity...
Doxorubicin-induced cardiotoxicity: direct correlation of cardiac fibroblast and H9c2 cell survival and aconitase activity with heat shock protein 27Samir Turakhia
Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA
Am J Physiol Heart Circ Physiol 293:H3111-21. 2007..Such a protection of aconitase by HSP27 eliminates the catalytic recycling of aconitase released Fe(II) and its deleterious effects in cardiac cells...
Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypassJohn S Giuliano
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
Intensive Care Med 34:1851-7. 2008..The aim was to investigate the effects of cardiopulmonary bypass (CPB) on plasma levels of the vascular growth factors, angiopoietin (angpt)-1, angpt-2, and vascular endothelial growth factor (VEGF)...
Hepatocyte NF-kappaB activation is hepatoprotective during ischemia-reperfusion injury and is augmented by ischemic hypothermiaSatoshi Kuboki
The Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 0558, USA
Am J Physiol Gastrointest Liver Physiol 292:G201-7. 2007....
Biomarkers for pediatric sepsis and septic shockStephen W Standage
Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Expert Rev Anti Infect Ther 9:71-9. 2011..Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities...
TranslationHector R Wong
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati Children's Research Foundation, Cincinnati, OH, USA
Crit Care Med 33:S404-6. 2005
Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cellsTimothy A Pritts
Department of Surgery, Ohio 45220, USA
Am J Physiol Regul Integr Comp Physiol 282:R1016-26. 2002....
Glutamine's protection against cellular injury is dependent on heat shock factor-1Angela L Morrison
Univ. of Colorado Health Sciences Center, Dept. of Anesthesiology, 4200 E. 9th Ave, Denver, CO 80262, USA
Am J Physiol Cell Physiol 290:C1625-32. 2006..Furthermore, the mechanism of GLN-mediated protection against injury appears to involve an increase in nuclear HSF-1 content before stress and increased HSF-1 promoter binding and phosphorylation...
Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cellsDerek S Wheeler
Section of Critical Care Medicine, Children s Medical Center, Medical College of Georgia, Augusta, GA 30912, USA
J Nutr 134:1039-44. 2004..Therefore, the green tea polyphenol EGCG is a potent inhibitor of IL-1 beta signal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65...
Validating the genomic signature of pediatric septic shockNatalie Cvijanovich
Children s Hospital and Research Center Oakland, Oakland, California, USA
Physiol Genomics 34:127-34. 2008..These data demonstrate that the previously reported genome-wide expression signature of pediatric septic shock is applicable to a validation cohort of patients...
Mast cell activation is differentially affected by heat shockEsmaeil Mortaz
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Exp Hematol 33:944-52. 2005..In this study, we further investigated the effects of heat shock on the activation of mast cells and the release of mast cell mediators...
Induction of HSP70 is dispensable for anti-inflammatory action of heat shock or NSAIDs in mast cellsEsmaeil Mortaz
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands
Exp Hematol 34:414-23. 2006..This prompted us to investigate whether NSAIDs modulate production of proinflammatory cytokines by mast cells through the heat shock response...
Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shockThomas P Shanley
C S Mott Children s Hospital at the University of Michigan, Ann Arbor, Michigan, USA
Mol Med 13:495-508. 2007..The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses...
Selectively increasing inducible heat shock protein 70 via TAT-protein transduction protects neurons from nitrosative stress and excitotoxicityYichen Lai
Department of Critical Care Medicine, The Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania, USA
J Neurochem 94:360-6. 2005..Further study is needed to confirm whether TAT-Hsp70 is protective in in vivo models of brain injury...
Stimulation of cysteinyl leukotriene production in mast cells by heat shock and acetylsalicylic acidEsmaeil Mortaz
Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P O BOX 80082, 3508 TB Utrecht, The Netherlands
Eur J Pharmacol 561:214-9. 2007..We conclude that heat shock and acetylsalicylic acid induce the production and release of heat shock proteins from mast cells, which in turn stimulate leukotriene synthesis through activation of TLR4...
Acetylsalicylic acid-induced release of HSP70 from mast cells results in cell activation through TLR pathwayEsmaeil Mortaz
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Exp Hematol 34:8-18. 2006..In the current study, we explored whether the stress response induces HSPs and affects the signaling pathways of mast cells...
Proteasome inhibitors induce inhibitory kappa B (I kappa B) kinase activation, I kappa B alpha degradation, and nuclear factor kappa B activation in HT-29 cellsZoltán H Németh
Department of Surgery, University of Medicine and Dentistry New Jersey Medical School, Newark, New Jersey 07103, USA
Mol Pharmacol 65:342-9. 2004..We conclude that the use of proteasome inhibitors to block NF-kappaB activation in cancer cells may not always be a viable approach...
Extracellular heat shock protein-70 induces endotoxin tolerance in THP-1 cellsRajesh Aneja
Department of Critical Care Medicine, University of Pittsburgh School of Medicine and Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
J Immunol 177:7184-92. 2006..HSP-70 preconditioning decreased phosphorylation of the p65 subunit of NF-kappaB following LPS stimulation. These data suggest a novel role for extracellular HSP-70 in modifying mononuclear cell responses to subsequent LPS challenge...
Pediatric septic shock treatment: new clues from genomic profilingHector R Wong
Pharmacogenomics 8:1287-90. 2007
The stress response decreases NF-kappaB activation in liver of endotoxemic miceTimothy A Pritts
Department of Surgery, University of Cincinnati, Ohio 45267 0558, USA
Shock 18:33-7. 2002..The present results suggest that the protective effects of the stress response in vivo may, at least in part, be due to inhibited NF-kappaB activation...
Yet another potential role for nitric oxide in the pathophysiology of septic shockMaeve Sheehan
Crit Care Med 30:1393-4. 2002
Research Grants
- Genomic analysis of pediatric SIRS and septic shockHector Wong; Fiscal Year: 2009..The data generated through this program will serve to substantially enhance our genome level understaning of SIRS and septic shock and provide the foundation for novel hypotheses, diagnostic approaches, and therapies. ..
- Genomic analysis of pediatric SIRS and septic shockHector Wong; Fiscal Year: 2007..The data generated through this program will serve to substantially enhance our genome level understaning of SIRS and septic shock and provide the foundation for novel hypotheses, diagnostic approaches, and therapies. ..
- The heat shock response and cytoprotectionHector Wong; Fiscal Year: 2006....
- Genomic Analysis of Pediatric SIRSHector Wong; Fiscal Year: 2005....
- INTERACTIONS BETWEEN HEAT SHOCK RESPONSE & NF-KBHector Wong; Fiscal Year: 2002....
- Genomic analysis of pediatric SIRS and septic shockHector Wong; Fiscal Year: 2009..Child health will be positively impacted by developing the capability of conducting zinc supplementation trials in a safe and rigorous manner. ..
