Hector Wong

Summary

Affiliation: Cincinnati Children's Hospital Medical Center
Country: USA

Publications

  1. doi request reprint The temporal version of the pediatric sepsis biomarker risk model
    Hector R Wong
    Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Cincinnati, Ohio, United States of America Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 9:e92121. 2014
  2. doi request reprint Testing the prognostic accuracy of the updated pediatric sepsis biomarker risk model
    Hector R Wong
    Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Cincinnati, Ohio, United States of America Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 9:e86242. 2014
  3. pmc Genome-wide expression profiling in pediatric septic shock
    Hector 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
  4. pmc Clinical review: sepsis and septic shock--the potential of gene arrays
    Hector 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
  5. pmc Genetics and genomics in pediatric septic shock
    Hector 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
  6. pmc Finding new therapies for sepsis: the need for patient stratification and the use of genetic biomarkers
    Michael 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
  7. pmc Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray
    Rajit 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
  8. pmc CpG DNA modulates interleukin 1beta-induced interleukin-8 expression in human bronchial epithelial (16HBE14o-) cells
    N William Parilla
    Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
    Respir Res 7:84. 2006
  9. pmc Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4
    Derek 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
  10. pmc Identification of pediatric septic shock subclasses based on genome-wide expression profiling
    Hector 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

Research Grants

Collaborators

Detail Information

Publications86

  1. doi request reprint The temporal version of the pediatric sepsis biomarker risk model
    Hector R Wong
    Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Cincinnati, Ohio, United States of America Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 9:e92121. 2014
    ..PERSEVERE is a risk model for estimating mortality probability in pediatric septic shock, using five biomarkers measured within 24 hours of clinical presentation...
  2. doi request reprint Testing the prognostic accuracy of the updated pediatric sepsis biomarker risk model
    Hector R Wong
    Division of Critical Care Medicine, Cincinnati Children s Hospital Medical Center and Cincinnati Children s Research Foundation, Cincinnati, Ohio, United States of America Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 9:e86242. 2014
    ..An important step in the development of updated risk models is to test their accuracy using an independent test cohort...
  3. pmc Genome-wide expression profiling in pediatric septic shock
    Hector 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...
  4. pmc Clinical review: sepsis and septic shock--the potential of gene arrays
    Hector 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...
  5. pmc Genetics and genomics in pediatric septic shock
    Hector 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...
  6. pmc Finding new therapies for sepsis: the need for patient stratification and the use of genetic biomarkers
    Michael 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...
  7. pmc Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray
    Rajit 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...
  8. pmc CpG DNA modulates interleukin 1beta-induced interleukin-8 expression in human bronchial epithelial (16HBE14o-) cells
    N 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...
  9. pmc Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4
    Derek 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...
  10. pmc Identification of pediatric septic shock subclasses based on genome-wide expression profiling
    Hector 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...
  11. pmc Leukocyte subset-derived genomewide expression profiles in pediatric septic shock
    Hector 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...
  12. pmc Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum
    Hector 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
    ....
  13. pmc Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock
    Hector 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...
  14. pmc Divergence of canonical danger signals: the genome-level expression patterns of human mononuclear cells subjected to heat shock or lipopolysaccharide
    Hector 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)...
  15. pmc Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome
    Hector 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...
  16. pmc Toward a clinically feasible gene expression-based subclassification strategy for septic shock: proof of concept
    Hector 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...
  17. pmc Validation of a gene expression-based subclassification strategy for pediatric septic shock
    Hector 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...
  18. ncbi request reprint Contribution of MKP-1 regulation of p38 to endotoxin tolerance
    Marianne 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...
  19. ncbi request reprint 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 activation
    Lauren Sanlorenzo
    Division of Critical Care Medicine, Children s Hospital Medical Center, Cincinnati, OH, USA
    Crit Care Med 32:2284-92. 2004
    ..We hypothesized that prior heat shock to monocytes would induce a phosphatase, MKP-1, that regulated mitogen-activated protein kinase activity and subsequently conferred cross-tolerance to lipopolysaccharide stimulation...
  20. ncbi request reprint Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damage
    Basilia 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...
  21. pmc Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats
    Rajesh 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...
  22. ncbi request reprint Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitis
    Patricia 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...
  23. ncbi request reprint Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents
    Maeve 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...
  24. pmc Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock
    Jennifer 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...
  25. ncbi request reprint Theaflavin, a black tea extract, is a novel anti-inflammatory compound
    Rajesh 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
    ..We determined the effects of theaflavin, a black tea-derived polyphenol, on tumor necrosis factor-alpha-mediated expression of the interleukin-8 gene in A549 cells...
  26. ncbi request reprint Heat shock inhibits activation of NF-kappaB in the absence of heat shock factor-1
    Vivek 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...
  27. pmc Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C
    James 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...
  28. ncbi request reprint Role of heat shock protein 70 in hepatic ischemia-reperfusion injury in mice
    Satoshi 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...
  29. ncbi request reprint Interactions between the heat shock response and the nuclear factor-kappa B signaling pathway
    Vivek 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...
  30. pmc Activation of hepatocytes by extracellular heat shock protein 72
    Elizabeth 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...
  31. pmc The role of endogenously produced extracellular hsp72 in mononuclear cell reprogramming
    Patricia 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...
  32. ncbi request reprint The green tea polyphenol epigallocatechin-3-gallate improves systemic hemodynamics and survival in rodent models of polymicrobial sepsis
    Derek 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...
  33. ncbi request reprint 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 Akt
    Basilia 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...
  34. doi request reprint Therapeutic application of intrapericardial tissue plasminogen activator in a 4-month-old child with complex fibropurulent pericarditis
    Michael 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...
  35. pmc Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock
    Derek 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...
  36. pmc Admission chemokine (C-C motif) ligand 4 levels predict survival in pediatric septic shock
    Jeffrey 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...
  37. pmc Age-related decrease in proteasome expression contributes to defective nuclear factor-kappaB activation during hepatic ischemia/reperfusion
    Nadine 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...
  38. pmc Lung injury after hemorrhage is age dependent: role of peroxisome proliferator-activated receptor gamma
    Basilia 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)...
  39. ncbi request reprint Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1
    Basilia 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...
  40. pmc Novel pharmacologic approaches to the management of sepsis: targeting the host inflammatory response
    Derek 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...
  41. pmc Induction of endotoxin tolerance enhances bacterial clearance and survival in murine polymicrobial sepsis
    Derek 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...
  42. ncbi request reprint Sesquiterpene lactone parthenolide, an inhibitor of IkappaB kinase complex and nuclear factor-kappaB, exerts beneficial effects in myocardial reperfusion injury
    Basilia 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...
  43. ncbi request reprint Molecular genetics in the pediatric intensive care unit
    Thomas 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...
  44. ncbi request reprint Heat shock-mediated regulation of MKP-1
    Hector 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...
  45. ncbi request reprint Parthenolide improves systemic hemodynamics and decreases tissue leukosequestration in rats with polymicrobial sepsis
    Maeve Sheehan
    Cincinnati Children s Hospital, OH, USA
    Crit Care Med 31:2263-70. 2003
    ..This study was designed to investigate the biological effects of parthenolide, a specific inhibitor of NF-kappaB activation, in experimental sepsis and multiple organ failure...
  46. ncbi request reprint A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB kinase activation and IL-8 gene expression in respiratory epithelium
    Philip 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...
  47. ncbi request reprint Temporal and mechanistic effects of heat shock on LPS-mediated degradation of IkappaBalpha in macrophages
    Bruce 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...
  48. ncbi request reprint Hyperoxia prolongs tumor necrosis factor-alpha-mediated activation of NF-kappaB: role of IkappaB kinase
    Hector 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...
  49. ncbi request reprint Phosphatase inhibition leads to activation of IkappaB kinase in murine macrophages
    Bruce 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...
  50. ncbi request reprint The A2A receptor mediates an endogenous regulatory pathway of cytokine expression in THP-1 cells
    Khaled 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...
  51. pmc Hsp72 induces inflammation and regulates cytokine production in airway epithelium through a TLR4- and NF-kappaB-dependent mechanism
    Margaret 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...
  52. ncbi request reprint Intracellular delivery of HSP70 using HIV-1 Tat protein transduction domain
    Derek 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
    ....
  53. ncbi request reprint Short-term modulation of interleukin-1beta signaling by hyperoxia: uncoupling of IkappaB kinase activation and NF-kappaB-dependent gene expression
    Kelli 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...
  54. ncbi request reprint Nuclear factor-kappaB as a therapeutic target in critical care medicine
    Basilia 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...
  55. doi request reprint An update and review of acute kidney injury in pediatrics
    Rajit 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...
  56. ncbi request reprint Age-dependent responses to hepatic ischemia/reperfusion injury
    Tomohisa 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...
  57. ncbi request reprint Ablation of the heat shock factor-1 increases susceptibility to hyperoxia-mediated cellular injury
    Vivek 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...
  58. pmc Pathophysiology and treatment of septic shock in neonates
    James 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...
  59. ncbi request reprint Extracellular hsp70 levels in children with septic shock
    Derek 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
    ..To determine whether hsp70 is elevated in the plasma of children with septic shock...
  60. pmc Mechanisms and regulation of the gene-expression response to sepsis
    Timothy 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...
  61. pmc Admission angiopoietin levels in children with septic shock
    John 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...
  62. pmc Heat shock response and acute lung injury
    Derek 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
    ....
  63. ncbi request reprint Heat shock inhibits tnf-induced ICAM-1 expression in human endothelial cells via I kappa kinase inhibition
    Gary 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...
  64. ncbi request reprint PP2A regulates upstream members of the c-jun N-terminal kinase mitogen-activated protein kinase signaling pathway
    Bin 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...
  65. ncbi request reprint Doxorubicin-induced cardiotoxicity: direct correlation of cardiac fibroblast and H9c2 cell survival and aconitase activity with heat shock protein 27
    Samir 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...
  66. pmc Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass
    John 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)...
  67. ncbi request reprint Hepatocyte NF-kappaB activation is hepatoprotective during ischemia-reperfusion injury and is augmented by ischemic hypothermia
    Satoshi 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
    ....
  68. pmc Biomarkers for pediatric sepsis and septic shock
    Stephen 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...
  69. ncbi request reprint Translation
    Hector 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
  70. ncbi request reprint Proteasome inhibitors induce heat shock response and increase IL-6 expression in human intestinal epithelial cells
    Timothy A Pritts
    Department of Surgery, Ohio 45220, USA
    Am J Physiol Regul Integr Comp Physiol 282:R1016-26. 2002
    ....
  71. ncbi request reprint Mast cell activation is differentially affected by heat shock
    Esmaeil 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...
  72. pmc Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock
    Thomas 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...
  73. ncbi request reprint Induction of HSP70 is dispensable for anti-inflammatory action of heat shock or NSAIDs in mast cells
    Esmaeil 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...
  74. ncbi request reprint Glutamine's protection against cellular injury is dependent on heat shock factor-1
    Angela 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...
  75. pmc Validating the genomic signature of pediatric septic shock
    Natalie 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...
  76. ncbi request reprint Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells
    Derek 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...
  77. ncbi request reprint Selectively increasing inducible heat shock protein 70 via TAT-protein transduction protects neurons from nitrosative stress and excitotoxicity
    Yichen 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...
  78. ncbi request reprint 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 cells
    Zoltán 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...
  79. ncbi request reprint Stimulation of cysteinyl leukotriene production in mast cells by heat shock and acetylsalicylic acid
    Esmaeil 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...
  80. ncbi request reprint Acetylsalicylic acid-induced release of HSP70 from mast cells results in cell activation through TLR pathway
    Esmaeil 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...
  81. ncbi request reprint Pediatric septic shock treatment: new clues from genomic profiling
    Hector R Wong
    Pharmacogenomics 8:1287-90. 2007
  82. ncbi request reprint Extracellular heat shock protein-70 induces endotoxin tolerance in THP-1 cells
    Rajesh 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...
  83. ncbi request reprint The stress response decreases NF-kappaB activation in liver of endotoxemic mice
    Timothy 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...
  84. ncbi request reprint Yet another potential role for nitric oxide in the pathophysiology of septic shock
    Maeve Sheehan
    Crit Care Med 30:1393-4. 2002

Research Grants14

  1. Genomic analysis of pediatric SIRS and septic shock
    Hector 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. ..
  2. Genomic analysis of pediatric SIRS and septic shock
    Hector 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. ..
  3. The heat shock response and cytoprotection
    Hector Wong; Fiscal Year: 2006
    ....
  4. Genomic Analysis of Pediatric SIRS
    Hector Wong; Fiscal Year: 2005
    ....
  5. INTERACTIONS BETWEEN HEAT SHOCK RESPONSE & NF-KB
    Hector Wong; Fiscal Year: 2002
    ....
  6. Genomic analysis of pediatric SIRS and septic shock
    Hector 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. ..