MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK

Summary

Principal Investigator: Timothy R Billiar
Abstract: Trauma is the leading cause of death in this country in people under the age of 54 years. Except for major head injury, hemorrhage/tissue trauma and its consequences are the most important causes of morbidity and mortality in these often young, otherwise healthy individuals. This Center Grant proposal seeks to advance our understanding of the molecular mechanisms leading to organ injury and dysfunction following trauma and hemorrhage. Our focus is on the events leading to the activation and propagation of inflammatory response with the view that the magnitude of the inflammatory response is the primary determinant of both early organ damage/dysfunction and delayed immune dysfunction following injury. Thus, understanding the inciting events could lead to effective approaches to limit not only the early organ damage but also the susceptibility to late sepsis and multiple organ failure (MOF). We propose that one of the keys to understanding organ injury resulting from hemorrhagic shock is to characterize the earliest molecular events leading to the initiation and propagation of inflammatory changes following the traumatic event. From previous funding cycles, we know that the initiation of inflammatory and stress signaling occurs quickly after the induction of shock and that the amplification of these responses involves a series of overlapping events. Our most recent efforts to identify the proximal steps have provided compelling evidence that pattern recognition receptors (PRR) of the innate immune system (Toll-like receptors) are engaged early following injury and both initiate and drive the inflammatory response. TLR4 and TLR9 are required for the activation of inflammatory signaling, while TLR2 and TLR4 are markedly unregulated and can induce an exaggerated inflammatory response if triggered by microbial ligands. Data from our PI's indicate tissue-specific expression and function patterns for TLR2 and TLR9. Endogenous activators of TLR signaling known as Damage-Associated Molecular Pattern (DAMP) molecules appear to drive the initial activation of TLR4 and TLR9. The nuclear protein high mobility group box-1 (HMGB1) is clearly involved in this process, and serves as an example of a prototypic DAMP in our trauma models. Thus, the danger signaling exemplified by the DAMP-PRR interaction represents a paradigm for the activation of the immune system post-injury. Much of the downstream signaling and organ response follows downstream from these initiating events. Our mechanism-driven approach has proven useful to identify some of the key pathways and mediators. However, as the quantity of information has expanded, we have recognized the need to integrate this information via a series of mathematical models that predict the relationship among key events. Constant refinement of these models will come from the incorporation of new experimental data and validation of experimental data in the clinical setting. Ultimately, these models guide the generation of new hypotheses. Just as the early molecular signaling events in trauma and shock are highly integrated, so is our research approach. Each of the five projects pursues a defined aspect of the host response to trauma and shock. All of the projects are integrated through well-established collaborative channels and co-reliance on three well-organized cores. Project I (Billiar) pursues the mechanisms involved in the activation of the systemic and hepatic inflammatory response emphasizing the roles of TLR4, TLR9, and HMGB1. Project II (Hackam) explores the roles of TLR4 and TLR9 in the dysfunction and damage to the Gl mucosa. Project III (Bauer) studies the mediators leading to gut motor function failure. This project explores the consequences of TLR2 upregulation on intestinal motility changes. Project IV (Fan) examines the pathways leading to the activation of the inflammasome post-injury, with a particular emphasis on TLR4 and HMGB1 in this process. Project V (Vodovotz/Ochoa) integrates the experimental findings into mathematical models of the injury response. Project V also links projects l-VI with the clinical side by gathering clinical data on trauma patients for incorporation into our most translational mathematical model, used for simulated clinical trials of promising therapies as well as for patient-specific outcome prediction. These collaborations and the overall goal of the center will be promoted significantly by the common use of three well-organized cores. The Animal Models Core (Core B) will provide a source of tissues from animals (primarily mice) subjected to standardized protocols of hemorrhagic shock and hemorrhage with tissue trauma under the supervision of technically experienced core personnel. This approach maintains consistency of the models between the projects and permits a detailed comparison of results. The Structural Imaging Core (Core C) will provide extraordinary expertise in state-of-the-art tissue imaging, including immunohistochemistry, confocal microscopy, electron microscopy, quantitative morphology, and in situ hybridization. Since each of the projects tests an individual hypothesis that seeks to identify the molecular events in tissues in hemorrhagic or traumatic shock, efficient and accurate structural imaging to localize these changes is essential to each investigator. The Administrative Core (Core A) will provide the critical organization needed to assure productive collaboration and communication. Based on our progress thus far, we are fully confident that our approach will continue to lead to productive collaboration and effective testing of a novel and important hypotheses.
Funding Period: 1998-06-01 - 2014-06-30
more information: NIH RePORT

Top Publications

  1. pmc Dominant role of the MyD88-dependent signaling pathway in mediating early endotoxin-induced murine ileus
    Bettina M Buchholz
    Dept of Medicine Gastroenterology Univ of Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Gastrointest Liver Physiol 299:G531-8. 2010
  2. pmc Matrix metalloproteinase-9 inhibition reduces inflammation and improves motility in murine models of postoperative ileus
    Beverley A Moore
    Johnson and Johnson Pharmaceutical Research Division, Spring House, Pennsylvania, USA
    Gastroenterology 141:1283-92, 1292.e1-4. 2011
  3. pmc Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis
    Rebecca D Edmonds
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Physiol Genomics 43:1170-83. 2011
  4. pmc Mast cells play a critical role in the systemic inflammatory response and end-organ injury resulting from trauma
    Changchun Cai
    Department of Hepatobiliary Surgery, Qingdao University Medical School Hospital, Qingdao, China
    J Am Coll Surg 213:604-15. 2011
  5. pmc Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis
    John B Seal
    Department of Surgery, University of Chicago, 5841 South Maryland Ave, MC 5031, Chicago, IL 60637, USA
    Theor Biol Med Model 8:33. 2011
  6. pmc Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells
    Meng Xiang
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 187:4809-17. 2011
  7. ncbi The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases
    Richard H Siggers
    Division of Pediatric Surgery, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
    Cell Mol Life Sci 68:3623-34. 2011
  8. pmc Biosimulation of acute phonotrauma: an extended model
    Nicole Y K Li
    Department of Surgery, University of Wisconsin Madison, Madison, Wisconsin, USA
    Laryngoscope 121:2418-28. 2011
  9. pmc Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model
    Moses Kim
    Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA
    Surg Infect (Larchmt) 13:18-32. 2012
  10. pmc Persistence of elevated plasma CXCL8 concentrations following red blood cell transfusion in a trauma cohort
    Janet S Lee
    Pulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Shock 37:373-7. 2012

Research Grants

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
  2. Thrombus Formation and Antithrombotic Intervention
    John H Griffin; Fiscal Year: 2013
  3. CENTER FOR BIOMEDICAL RESEARCH
    Timothy Turner; Fiscal Year: 2013
  4. Overall Application: Trauma Primes Cells
    Anirban Banerjee; Fiscal Year: 2013
  5. PATHOPHYSIOLOGY OF THE ENDOTHELIUM
    Francis W Luscinskas; Fiscal Year: 2013
  6. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
  7. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
  8. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
  9. Improving Cardiac Function After Myocardial Infarction
    Steven R Houser; Fiscal Year: 2013
  10. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013

Detail Information

Publications148 found, 100 shown here

  1. pmc Dominant role of the MyD88-dependent signaling pathway in mediating early endotoxin-induced murine ileus
    Bettina M Buchholz
    Dept of Medicine Gastroenterology Univ of Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Gastrointest Liver Physiol 299:G531-8. 2010
    ..The dependency of ileus on individual adaptor protein pathways is also reflected in the manifestation of specific molecular inflammatory events within the intestinal muscularis externa...
  2. pmc Matrix metalloproteinase-9 inhibition reduces inflammation and improves motility in murine models of postoperative ileus
    Beverley A Moore
    Johnson and Johnson Pharmaceutical Research Division, Spring House, Pennsylvania, USA
    Gastroenterology 141:1283-92, 1292.e1-4. 2011
    ..We evaluated the role of MMP-9 in POI and investigated whether disruption of MMP-9 or administration of an inhibitor of MMP-9 activity reduced cellular inflammation and bowel dysmotility in rat and mouse models of POI...
  3. pmc Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis
    Rebecca D Edmonds
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Physiol Genomics 43:1170-83. 2011
    ..This is the first study to examine the postinjury response using dual-platform microarray analysis, revealing responses that may enable novel therapies or diagnostics...
  4. pmc Mast cells play a critical role in the systemic inflammatory response and end-organ injury resulting from trauma
    Changchun Cai
    Department of Hepatobiliary Surgery, Qingdao University Medical School Hospital, Qingdao, China
    J Am Coll Surg 213:604-15. 2011
    ..This is manifested as a systemic inflammatory response and associated end-organ damage. Although mast cells are known to be important in many immune responses, their role in the systemic response to severe trauma is unknown...
  5. pmc Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis
    John B Seal
    Department of Surgery, University of Chicago, 5841 South Maryland Ave, MC 5031, Chicago, IL 60637, USA
    Theor Biol Med Model 8:33. 2011
    ..We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis...
  6. pmc Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells
    Meng Xiang
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 187:4809-17. 2011
    ..The present study explores a novel mechanism underlying HS activation of EC inflammasome and thus presents a potential therapeutic target for SIRS and ALI induced after HS...
  7. ncbi The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases
    Richard H Siggers
    Division of Pediatric Surgery, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
    Cell Mol Life Sci 68:3623-34. 2011
    ..This review will detail the regulatory pathways that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis in gastrointestinal disease...
  8. pmc Biosimulation of acute phonotrauma: an extended model
    Nicole Y K Li
    Department of Surgery, University of Wisconsin Madison, Madison, Wisconsin, USA
    Laryngoscope 121:2418-28. 2011
    ..The central aim of the present study was to investigate the utility of mechanistic computational modeling of inflammation and healing to address personalized therapy for patients with acute phonotrauma...
  9. pmc Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model
    Moses Kim
    Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA
    Surg Infect (Larchmt) 13:18-32. 2012
    ..The multi-factorial complexity of NEC requires characterization with computational modeling, and herein, we used an agent-based model (ABM) to instantiate and examine our unifying hypothesis of the pathogenesis of NEC...
  10. pmc Persistence of elevated plasma CXCL8 concentrations following red blood cell transfusion in a trauma cohort
    Janet S Lee
    Pulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Shock 37:373-7. 2012
    ..Other bioanalytes showed no differences across time. Red blood cell transfusion is associated with persistently elevated neutrophil chemokine CXCL8 concentrations following traumatic injury...
  11. pmc Role of macrophages in mobilization of hematopoietic progenitor cells from bone marrow after hemorrhagic shock
    Meng Xiang
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Shock 37:518-23. 2012
    ..These data indicate that HS/R, a global ischemia-reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuroendocrine and innate immune systems, in which Mϕ play a central role...
  12. pmc A two-compartment mathematical model of endotoxin-induced inflammatory and physiologic alterations in swine
    Gary Nieman
    Department of Surgery, Upstate Medical University, Syracuse, NY, USA
    Crit Care Med 40:1052-63. 2012
    ..To gain insights into individual variations in acute inflammation and physiology...
  13. pmc Physiologic responses to severe hemorrhagic shock and the genesis of cardiovascular collapse: can irreversibility be anticipated?
    Hernando Gomez
    Department of Critical Care Medicine, University of Pittsburgh, 3550 Terrace Street, Scaife Hall, Pittsburgh, PA 15261, USA
    J Surg Res 178:358-69. 2012
    ..We hypothesized that vascular tone loss characterizes CC, and that arterial pulse pressure/stroke volume index ratio or vascular tone index (VTI) would identify CC...
  14. pmc Role of interleukin-6 in hemopoietic and non-hemopoietic synergy mediating TLR4-triggered late murine ileus and endotoxic shock
    B M Buchholz
    Department of Medicine Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Neurogastroenterol Motil 24:658-69, e294. 2012
    ..Our objective was to define the role of hemopoietic cells in LPS/TLR4-triggered ileus and inflammation over time, and identify mechanisms of ileus...
  15. pmc Differential molecular and cellular immune mechanisms of postoperative and LPS-induced ileus in mice and rats
    Joachim Schmidt
    Department of Medicine Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Cytokine 59:49-58. 2012
    ..Whereas, the more intense mouse ileus evolves via a potent but injury-specific local cytokine response...
  16. pmc Mammalian DNA is an endogenous danger signal that stimulates local synthesis and release of complement factor B
    David J Kaczorowski
    Division of Cardiovascular Surgery, University of Pennsylvania, Philadelphia, PA, United States of America
    Mol Med 18:851-60. 2012
    ..This activation of the immune system likely contributes to damage following sterile injury such as hemorrhagic shock and ischemia-reperfusion...
  17. pmc Caspase-1 is hepatoprotective during trauma and hemorrhagic shock by reducing liver injury and inflammation
    Christoph L Menzel
    Department of Orthopedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Mol Med 17:1031-8. 2011
    ..These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF)...
  18. pmc A dynamic view of trauma/hemorrhage-induced inflammation in mice: principal drivers and networks
    Qi Mi
    Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 6:e19424. 2011
    ..We utilized multiplexing cytokine analysis coupled with data-driven modeling to gain a systems perspective into T/HS...
  19. pmc Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells
    Roop Gill
    Department of Surgery, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Shock 35:164-70. 2011
    ..These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9...
  20. pmc Biosimulation of inflammation and healing in surgically injured vocal folds
    Nicole Y K Li
    Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Ann Otol Rhinol Laryngol 119:412-23. 2010
    ..The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx...
  21. pmc Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome
    Changchun Cai
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1175-82. 2010
    ..Our data indicate that complement activation contributes to inflammatory pathways and liver damage in HS/T. This suggests that targeting complement activation in the setting of severe injury could be useful...
  22. ncbi Systems biology and inflammation
    Yoram Vodovotz
    Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine and Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    Methods Mol Biol 662:181-201. 2010
    ..This chapter reviews the existing, translational applications of computational simulations and related approaches as applied to inflammation...
  23. pmc Agent-based models in translational systems biology
    Gary An
    Department of Surgery, Northwestern University, Chicago, IL 60611, USA
    Wiley Interdiscip Rev Syst Biol Med 1:159-71. 2009
    ..This review describes agent-based modeling and gives examples of its translational applications in the context of acute inflammation and wound healing...
  24. pmc Anti-inflammatory role of glycine in reducing rodent postoperative inflammatory ileus
    B Stoffels
    Department of Medicine Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Neurogastroenterol Motil 23:76-87, e8. 2011
    ..Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis...
  25. pmc DNA attenuates enterocyte Toll-like receptor 4-mediated intestinal mucosal injury after remote trauma
    Chhinder Sodhi
    Div of Pediatric Surgery, Department of Surgery, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15224, USA
    Am J Physiol Gastrointest Liver Physiol 300:G862-73. 2011
    ....
  26. pmc Cytoprotective effects of albumin, nitrosated or reduced, in cultured rat pulmonary vascular cells
    Hui Hua Li
    Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Am J Physiol Lung Cell Mol Physiol 300:L526-33. 2011
    ....
  27. pmc Models of lower extremity damage in mice: time course of organ damage and immune response
    Christoph L Menzel
    Department of Orthopedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
    J Surg Res 166:e149-56. 2011
    ..This follow-up study tests the hypothesis that inflammatory responses are comparable between a novel trauma model ("pseudofracture", PFx) and a bilateral femur fracture (BFF) model...
  28. pmc Continuum model of collective cell migration in wound healing and colony expansion
    Julia C Arciero
    Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Biophys J 100:535-43. 2011
    ....
  29. pmc Novel model of peripheral tissue trauma-induced inflammation and gastrointestinal dysmotility
    T Tsukamoto
    Department of Medicine Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Neurogastroenterol Motil 23:379-86, e164. 2011
    ..Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed...
  30. pmc Hypoxia-induced overexpression of BNIP3 is not dependent on hypoxia-inducible factor 1α in mouse hepatocytes
    Rajaie A Namas
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Shock 36:196-202. 2011
    ..These results suggest that HIF-1α does not mediate the hypoxia-induced upregulation of BNIP3 in mouse hepatocytes in vitro and possibly in the liver in vivo...
  31. ncbi Toward computational identification of multiscale "tipping points" in acute inflammation and multiple organ failure
    Gary An
    Department of Surgery, University of Chicago, Chicago, IL 60637, USA
    Ann Biomed Eng 40:2414-24. 2012
    ....
  32. pmc Hemoadsorption reprograms inflammation in experimental gram-negative septic peritonitis: insights from in vivo and in silico studies
    Rami A Namas
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States of America
    Mol Med 18:1366-74. 2012
    ..Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammatory compartmentalization in Escherichia coli-induced fibrin peritonitis in rats...
  33. pmc Selective roles for toll-like receptors 2, 4, and 9 in systemic inflammation and immune dysfunction following peripheral tissue injury
    Sophie S Darwiche
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    J Trauma Acute Care Surg 74:1454-61. 2013
    ..Although TLRs are known to modulate innate immune responses, their role in the suppression of lymphocyte responses following traumatic tissue injury is unclear...
  34. pmc TIFA upregulation after hypoxia-reoxygenation is TLR4- and MyD88-dependent and associated with HMGB1 upregulation and release
    Ning Ding
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Free Radic Biol Med 63:361-7. 2013
    ..The increase in TIFA level appears to be a feed-forward mechanism involved in TLR4/MyD88-dependent signaling, leading to NF-κB activation and HMGB1 release. ..
  35. pmc TLR4 Signaling augments monocyte chemotaxis by regulating G protein-coupled receptor kinase 2 translocation
    Zheng Liu
    Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China
    J Immunol 191:857-64. 2013
    ..This results in enhanced monocyte migration. These findings reveal a novel function for TLR4 signaling in promoting innate immune cell migration. ..
  36. pmc Discovery and validation of a new class of small molecule Toll-like receptor 4 (TLR4) inhibitors
    Matthew D Neal
    Division of Pediatric Surgery Children s Hospital of Pittsburgh and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e65779. 2013
    ..These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases...
  37. ncbi Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma
    Sebastian Korff
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Department of Trauma Surgery, University of Heidelberg, Heidelberg, Germany
    J Surg Res 184:e17-25. 2013
    ....
  38. pmc Combined in silico, in vivo, and in vitro studies shed insights into the acute inflammatory response in middle-aged mice
    Rami A Namas
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    PLoS ONE 8:e67419. 2013
    ....
  39. pmc In silico modeling: methods and applications to trauma and sepsis
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    Crit Care Med 41:2008-14. 2013
    ..To familiarize clinicians with advances in computational disease modeling applied to trauma and sepsis...
  40. pmc Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study
    Wan Huang
    Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA The Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh, PA
    PM R 6:332-41. 2014
    ..Macrophage phenotype has been characterized as either proinflammatory (M1) or anti-inflammatory (M2). Results of animal studies suggest that M1 or M2 dominance at the site of injury relates to spontaneous recovery after SCI...
  41. pmc Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells
    Hui Hua Li
    Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e81903. 2013
    ....
  42. pmc Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies
    Cordelia Ziraldo
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Joint Carnegie Mellon University University of Pittsburgh Ph D Program in Computational Biology, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e79804. 2013
    ....
  43. pmc Inducible protein-10, a potential driver of neurally controlled interleukin-10 and morbidity in human blunt trauma
    Akram M Zaaqoq
    1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 2Department of Surgery, University of Pittsburgh, Pittsburgh, PA 3Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 4Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA 5Department of Rehabilitation Science and Technology, University of Pittsburgh, Pittsburgh, PA 6Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
    Crit Care Med 42:1487-97. 2014
    ..We used in silico methods to discern dynamic inflammatory networks that could distinguish systemic inflammation in traumatic spinal cord injury from blunt trauma...
  44. pmc Investigation of inflammation and tissue patterning in the gut using a Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT)
    Chase Cockrell
    Department of Surgery, University of Chicago, Chicago, Illinois, United States of America
    PLoS Comput Biol 10:e1003507. 2014
    ..These results suggest that SEGMEnT can serve as an integrating platform for the study of inflammation in gastrointestinal disease. ..
  45. pmc From data patterns to mechanistic models in acute critical illness
    Jean Marie Aerts
    Division Measure, Model and Manage Bioresponses M3 BIORES, Department of Biosystems, KU Leuven, Leuven, Belgium B 3001
    J Crit Care 29:604-10. 2014
    ..As a predicate example, we focus on the role of data-driven and mechanistic models in neuroscience and the impact that merging these modeling approaches can have on general anesthesia. ..
  46. pmc Evidence-based feeding strategies before and after the development of necrotizing enterocolitis
    Misty Good
    Department of Pediatrics, Division of Newborn Medicine, Children s Hospital of Pittsburgh, Pittsburgh, PA, USA
    Expert Rev Clin Immunol 10:875-84. 2014
    ..This review will focus on the mechanisms by which breast milk may serve to protect against NEC, and will review the evidence regarding various feeding strategies that may be utilized before and after an episode of NEC...
  47. ncbi Age-independent co-expression of antimicrobial gene clusters in the blood of septic patients
    Sandro Lindig
    Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany
    Int J Antimicrob Agents 42:S2-7. 2013
    ..Results of this transcriptomic meta-analysis suggest age-independent diagnostic opportunities, although further observational and animal interventional experiments are required to confirm the relevance of antimicrobial genes in sepsis...
  48. pmc CD14 contributes to warm hepatic ischemia-reperfusion injury in mice
    Changchun Cai
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Shock 40:115-21. 2013
    ..CD14 is known to participate in the function of TLR4. We hypothesized that CD14 would be involved in the pathobiology of warm hepatic I/R...
  49. pmc Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS-NO-nitrite signaling
    Ibrahim Yazji
    Division of Pediatric Surgery, Children s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
    Proc Natl Acad Sci U S A 110:9451-6. 2013
    ....
  50. pmc Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice
    Chhinder P Sodhi
    Division of Pediatric Surgery, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15224, USA
    Gastroenterology 143:708-18.e1-5. 2012
    ..We investigated whether intestinal TLR4 regulates epithelial differentiation and is involved in development of necrotizing enterocolitis (NEC) of the immature intestine...
  51. pmc Identification of a novel pathway of transforming growth factor-β1 regulation by extracellular NAD+ in mouse macrophages: in vitro and in silico studies
    Ruben Zamora
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 287:31003-14. 2012
    ..Thus, in vitro and in silico evidence points to NAD(+) as a novel modulator of TGF-β1...
  52. pmc Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis
    Matthew D Neal
    Division of Pediatric Surgery Children s Hospital of Pittsburgh and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA
    J Biol Chem 287:37296-308. 2012
    ..These findings illustrate that TLR4 is expressed on ISCs where it regulates their proliferation and apoptosis through activation of PUMA and that TLR4 regulation of ISCs contributes to the pathogenesis of necrotizing enterocolitis...
  53. pmc Iatrogenic extracellular matrix disruption as a local trigger for postoperative ileus
    Johannes Chang
    Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany
    J Surg Res 178:632-9. 2012
    ..In this study, we investigated the inflammatory role of MMP-9 and the ECM breakdown product hyaluronan as a trigger for the postoperative intestinal inflammatory response of postoperative ileus...
  54. pmc Integration of TGF-β- and EGFR-based signaling pathways using an agent-based model of epithelial restitution
    Jordan R Stern
    Department of Surgery, The University of Chicago, Chicago, Illinois 60622, USA
    Wound Repair Regen 20:862-71. 2012
    ..This highlights the utility of dynamic knowledge representation in the integration of pathways previously studied in separate contexts...
  55. pmc Sepsis: from pattern to mechanism and back
    Gary An
    Department of Surgery, University of Chicago, Chicago, IL 60637, USA
    Crit Rev Biomed Eng 40:341-51. 2012
    ....
  56. pmc High mobility group Box 1 inhibits human pulmonary artery endothelial cell migration via a Toll-like receptor 4- and interferon response factor 3-dependent mechanism(s)
    Eileen M Bauer
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 288:1365-73. 2013
    ..These data demonstrate that HMGB1 inhibits HPAEC migration, a critical process for vascular regeneration, via TLR4- and IRF3-dependent mechanisms...
  57. pmc A three-dimensional mathematical and computational model of necrotizing enterocolitis
    Jared Barber
    Department of Mathematics, 301 Thackeray Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA
    J Theor Biol 322:17-32. 2013
    ....
  58. pmc High mobility group box 1 contributes to the pathogenesis of experimental pulmonary hypertension via activation of Toll-like receptor 4
    Eileen M Bauer
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States of America
    Mol Med 18:1509-18. 2012
    ..These data demonstrate that HMGB1-mediated activation of TLR4 promotes experimental PH and identify HMGB1 and/or TLR4 as potential therapeutic targets for the treatment of PH...
  59. ncbi Using a continuum model to predict closure time of gaps in intestinal epithelial cell layers
    Julia C Arciero
    Department of Mathematical Sciences, Indiana University Purdue University, Indianapolis, IN 46202 3267, USA
    Wound Repair Regen 21:256-65. 2013
    ..In this study, data from scratch assays suggest that the rate of change of area is proportional to the first power or square root power of area...
  60. pmc A critical role for TLR4 induction of autophagy in the regulation of enterocyte migration and the pathogenesis of necrotizing enterocolitis
    Matthew D Neal
    Division of Pediatric Surgery, Department of Surgery, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA
    J Immunol 190:3541-51. 2013
    ....
  61. pmc Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice
    Gary W Nace
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA
    Hepatology 58:374-87. 2013
    ....
  62. pmc Hemorrhagic shock augments Nlrp3 inflammasome activation in the lung through impaired pyrin induction
    Peng Xu
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 190:5247-55. 2013
    ..This study demonstrates a novel mechanism by which HS suppresses negative-feedback regulation of Nlrp3 inflammasome to enhance IL-1β secretion in response to subsequent LPS challenge and so primes for inflammation...
  63. pmc Caspase 1 activation is protective against hepatocyte cell death by up-regulating beclin 1 protein and mitochondrial autophagy in the setting of redox stress
    Qian Sun
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 288:15947-58. 2013
    ....
  64. pmc Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch
    David J Hackam
    Department of Surgery, Division of Pediatric Surgery, Children s Hospital of Pittsburgh and University of Pittsburgh School of Medicine, One Children s Hospital Drive, 4401 Penn Avenue, Pittsburgh, Pennsylvania 15224, USA
    Semin Pediatr Surg 22:76-82. 2013
    ....
  65. pmc Global sensitivity analysis of a mathematical model of acute inflammation identifies nonlinear dependence of cumulative tissue damage on host interleukin-6 responses
    Shibin Mathew
    Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA Electronic address
    J Theor Biol 358:132-48. 2014
    ....
  66. ncbi Nitric oxide-induced nuclear translocation of the metal responsive transcription factor, MTF-1 is mediated by zinc release from metallothionein
    Molly S Stitt
    Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, 100 Technology Drive, Cellomics Building, Room 335, Pittsburgh, PA 15260, USA
    Vascul Pharmacol 44:149-55. 2006
    ..These data suggest that S-nitrosation of Zn-thiolate clusters in MT and subsequent alterations in Zn homeostasis are participants in intracellular NO signaling pathways affecting gene expression...
  67. ncbi Ethyl pyruvate: a novel anti-inflammatory agent
    M P Fink
    Departments of Critical Care Medicine, Pharmacology and Surgery, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA
    J Intern Med 261:349-62. 2007
    ..EP has been tested in human volunteers and shown to be safe at clinically relevant doses. It remains to be determined whether EP can be used successfully to treat human diseases...
  68. ncbi A novel inhibitory peptide of Toll-like receptor signaling limits lipopolysaccharide-induced production of inflammatory mediators and enhances survival in mice
    Allan Tsung
    Departments of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Shock 27:364-9. 2007
    ..These results demonstrated the therapeutic potential of peptide P13 to limit an LPS-induced inflammatory response and enhance survival in murine models of inflammation...
  69. pmc Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery
    Andreas Türler
    Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Ann Surg 245:734-44. 2007
    ..To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus...
  70. ncbi Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling
    Jie Fan
    Department of Surgery, School of Medicine, University of Pittsburgh, and Division of Pediatric Surgery, Children s Hospital of Pittsburgh, PA 15213, USA
    J Immunol 178:6573-80. 2007
    ..Thus, PMN NAD(P)H oxidase activation, induced by HS/R and as mediated by HMGB1/TLR4 signaling, is an important mechanism responsible for PMN-mediated inflammation and organ injury after hemorrhage...
  71. ncbi Neutrophil NAD(P)H oxidase is required for hemorrhagic shock-enhanced TLR2 up-regulation in alveolar macrophages in response to LPS
    Jie Fan
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15240, USA
    Shock 28:213-8. 2007
    ..Thus, PMN nicotinamide adenine dinucleotide phosphate (reduced form) oxidase sensitizes hemorrhagic shock-primed AM to LPS, at least in part via enhancing IL-1 receptor associated kinase 4 activity...
  72. ncbi Hypoxia activates c-Jun N-terminal kinase via Rac1-dependent reactive oxygen species production in hepatocytes
    Kevin P Mollen
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Shock 28:270-7. 2007
    ..Together, these data suggest that ROS generation during hypoxia in the liver directly leads to JNK activation in a Rac1-dependent process...
  73. pmc Challenges and rewards on the road to translational systems biology in acute illness: four case reports from interdisciplinary teams
    Gary An
    Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    J Crit Care 22:169-75. 2007
    ..However, the development of these groups must overcome domain-specific barriers to communication and understanding...
  74. ncbi Systemic inflammation and remote organ injury following trauma require HMGB1
    Ryan M Levy
    Dept of Surgery, F 1200 PUH, Univ of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1538-44. 2007
    ..Collectively, these data demonstrate a critical role for a TLR4-HMGB1 pathway in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury...
  75. pmc One-dimensional elastic continuum model of enterocyte layer migration
    Qi Mi
    Department of Mathematics, Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Biophys J 93:3745-52. 2007
    ..The model is applicable to the closure of a wound with a linear edge and, after calibration with experimental data, could be used to predict the effect of chemical agents on mobility, adhesion, and proliferation of enterocytes...
  76. ncbi Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells
    Kevin P Mollen
    Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15217, USA
    J Leukoc Biol 83:80-8. 2008
    ..These data demonstrate that functional TLR4 is required in BM-derived cells and parenchymal cells for an optimal inflammatory response to trauma...
  77. ncbi Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-beta1
    Qi Mi
    Department of Mathematics, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Wound Repair Regen 15:671-82. 2007
    ..reduced TGF-beta1). In silico methods may elucidate mechanisms of and suggest therapies for aberrant skin healing...
  78. pmc HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 204:2913-23. 2007
    ..Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling...
  79. ncbi FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells
    Qiuhong Zhang
    Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, PA 15261, USA
    Cardiovasc Res 77:560-9. 2008
    ..In this study, we examine the effect of FXR ligands on the angiotensin system in rat aortic SMC (RASMC), as angiotensin II (Ang II) signalling contributes to various types of vascular lesions by promoting cell growth of vascular SMC...
  80. ncbi FXR-mediated regulation of eNOS expression in vascular endothelial cells
    Jiang Li
    Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, PA 15261, USA
    Cardiovasc Res 77:169-77. 2008
    ..In the present study, we examine whether activation of FXR also affects the expression of endothelial nitric oxide synthase (eNOS) in rat, bovine, and sheep vascular EC...
  81. ncbi Toll-like receptor 4 mediates the early inflammatory response after cold ischemia/reperfusion
    David J Kaczorowski
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Transplantation 84:1279-87. 2007
    ..We tested the hypothesis that TLR4 mediates the early inflammatory response in the setting of cold I/R in a murine cardiac transplant model...
  82. ncbi Alvimopan and COX-2 inhibition reverse opioid and inflammatory components of postoperative ileus
    J Schmidt
    Department of Medicine Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Neurogastroenterol Motil 20:689-99. 2008
    ....
  83. pmc Evidence-based modeling of critical illness: an initial consensus from the Society for Complexity in Acute Illness
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Crit Care 22:77-84. 2007
    ..Accordingly, SCAI identified a need for and carried out a critical appraisal of DMM as currently used in the setting of acute illness...
  84. ncbi Altered inflammatory gene expression underlies increased susceptibility to murine postoperative ileus with advancing age
    Beverley A Moore
    Dept of Medicine Gastroenterology, Univ of Pittsburgh Medical School, S849 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA
    Am J Physiol Gastrointest Liver Physiol 292:G1650-9. 2007
    ..Such imbalances between pro- and anti-inflammatory mechanisms may form the basis for increased susceptibility to ileus and for the increased severity and duration of ileus observed in the elderly...
  85. ncbi Deciphering the complexity of acute inflammation using mathematical models
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, and Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
    Immunol Res 36:237-45. 2006
    ..Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics...
  86. ncbi Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock
    Jose M Prince
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Am Coll Surg 202:407-17. 2006
    ..We sought to determine the role of lipolysaccharide through use of CD14-/- mice...
  87. ncbi Biliverdin protects against polymicrobial sepsis by modulating inflammatory mediators
    Marcus Overhaus
    Department of Medicine Gastroenterology, University of Pittsburgh, PA 15261, USA
    Am J Physiol Gastrointest Liver Physiol 290:G695-703. 2006
    ..These findings demonstrate that biliverdin attenuates sepsis-induced morbidity to the intestine by selectively modulating the inflammatory cascade and its subsequent sequelae on intestinal muscularis function...
  88. ncbi A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration
    Judy Day
    Department of Mathematics, 301 Thackeray, University of Pittsburgh, Pittsburgh, PA 15260, USA
    J Theor Biol 242:237-56. 2006
    ....
  89. ncbi Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4
    Ryan M Levy
    Department of Surgery, F 1200 PUH, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15217, USA
    Am J Physiol Regul Integr Comp Physiol 291:R970-6. 2006
    ..Application of these findings in an evolutionary context suggests that multicellular organisms have evolved to use the same pattern recognition receptor for surviving traumatic and infectious challenges...
  90. ncbi The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock
    Kathleen G Raman
    Univ of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 291:G556-65. 2006
    ..Circulating IL-10 levels were higher in rage(-/-) compared with rage(+/+) mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R...
  91. ncbi Cutting edge: high-mobility group box 1 preconditioning protects against liver ischemia-reperfusion injury
    Kunihiko Izuishi
    Department of Surgery, University of Pittsburgh, PA 15213, USA
    J Immunol 176:7154-8. 2006
    ..Our studies demonstrate that in contrast to the role of HMGB1 as an early mediator of inflammation and organ damage in hepatic I/R, HMGB1 preconditioning can be protective...
  92. pmc Leukocyte-derived inducible nitric oxide synthase mediates murine postoperative ileus
    Andreas Türler
    Department of Medicine, Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA, USA
    Ann Surg 244:220-9. 2006
    ..To provide evidence that iNOS expression solely in leukocytes plays a role in postoperative ileus...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. Thrombus Formation and Antithrombotic Intervention
    John H Griffin; Fiscal Year: 2013
    ..New knowledge will contribute to improving prevention, diagnosis and treatment of relevant diseases related to thrombosis. ..
  3. CENTER FOR BIOMEDICAL RESEARCH
    Timothy Turner; Fiscal Year: 2013
    ..abstract_text> ..
  4. Overall Application: Trauma Primes Cells
    Anirban Banerjee; Fiscal Year: 2013
    ....
  5. PATHOPHYSIOLOGY OF THE ENDOTHELIUM
    Francis W Luscinskas; Fiscal Year: 2013
    ..g., heart attacks and strokes), as well as other organs and tissues of the body. These mechanistic insights may help identify novel therapeutic targets for the treatment of a broad spectrum of inflammatory diseases. ..
  6. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
    ..abstract_text> ..
  7. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
    ..The insights gained from the data generated from these studies will provide novel molecular targets for the development of new therapeutic strategies to treat patients with lung injury. ..
  8. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  9. Improving Cardiac Function After Myocardial Infarction
    Steven R Houser; Fiscal Year: 2013
    ..A gene vector core will generate AAV6 vectors with novel therapeutics for testing in the pig Ml model. An administrative core will ensure data sharing and effective use of all resources. ..
  10. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....