Dr. Ayala is Professor of Surgery (Research) at Rhode Island Hospital/the Alpert School of Medicine at Brown University. He serves as a standing member of the National Institutes of Health (NIH)-Lung Cellular Molecular & Immunology (LCMI)-Study Section as well as previously on the NIH-Surgery Anesthesia Trauma (SAT)-Study Section, and has served as an ad hoc on various NIH site visit teams/SEPs/ad hoc review pannels, the Veteran's Administration (VA)-Department of Defense (DoD) Merit Review Board, Wellcome Trust as well as Shriners Research Hospitals. He has been recognized by his peers through election to President (04'-05'), Treasurer (02'-04'), and Scientific Program Chairman (01) of the Shock Society; as selection as Recorder/Executive Council (05'-07') of the Surgical Infection Society, and by appointment to the Society of Leukocyte Biology council (11'-13'). Dr. Ayala was also the recipient of a "Maximizing Investigators' Research Award (R35)" from the NIH-NIGMS (16'); the Shock Society's 10th annual 'Scientific Achievement Award' (07'); and the 15th annual 'Distinquished Service Award' (09'). He has over 300 manuscripts/review articles to his credit and has been continuously funded by the NIH since 1991. He is also a member of the training faculty of the Brown University Graduate Pathobiology Program; the Department of Pharmacology, Physiology & Biotechnology graduate program; and is an adjunct Professor/mentor in the Univ. R.I. graduate program in the Department of Cellular & Molecular Biology. During his tenure at Brown University and previously at Michigan State University he has had the privilege of mentoring students ranging from undergraduates and medical students to surgical residents, post-doctoral fellows and Junior Faculty. Research interests include projects looking at: the differential effects of sepsis on immune cell function; the role of programmed cell death/ apoptosis in immune dysfunction observed following hemorrhage and/or sepsis; as well as, the contribution of 'check-point' protein/ accessory molecule expression to the pathological process mediating acute lung injury resultant from shock and/or septic insults.
|Bruns, Bastian, Hönle, Theresia, Kellermann, Philipp, Ayala, Alfred, Perl, Mario Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage. SHOCK/Shock. 2017; 47 (2) : 225-235.|
|Sakhatskyy P, Wang Z, Borgas D, Lomas-Neira J, Chen Y, Ayala A, Rounds S, Lu Q Double-hit mouse model of cigarette smoke priming for acute lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology/AJP: Lung Cellular and Molecular Physiology. 2017; 312 (1) : ajplung.00436.2016.|
|Wu Y, Chung CS, Chen Y, Monaghan SF, Patel S, Huang X, Heffernan DS, Ayala A A Novel Role for Programmed Cell Death Receptor Ligand-1 (PD-L1) in Sepsis-Induced Intestinal Dysfunction.. Molecular medicine (Cambridge, Mass.). 2016; 22|
|Lomas-Neira JL, Heffernan DS, Ayala A, Monaghan SF BLOCKADE OF ENDOTHELIAL GROWTH FACTOR, ANGIOPOIETIN-2, REDUCES INDICES OF ARDS AND MORTALITY IN MICE RESULTING FROM THE DUAL-INSULTS OF HEMORRHAGIC SHOCK AND SEPSIS. Shock. 2016; 45 (2) : 157-165.|
|Biron BM, Chung CS, O'Brien XM, Chen Y, Reichner JS, Ayala A Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model.. Journal of innate immunity. 2016;|
|Wang F, Huang X, Chung CS, Chen Y, Hutchins NA, Ayala A Contribution of Programmed Cell Death Receptor (PD)-1 to Kupffer Cell Dysfunction in Murine Polymicrobial Sepsis.. American journal of physiology. Gastrointestinal and liver physiology. 2016; : ajpgi.00371.2015.|
|Cheng T, Bai J, Chung CS, Chen Y, Biron BM, Ayala A Enhanced Innate Inflammation Induced by Anti-BTLA Antibody in Dual Insult Model of Hemorrhagic Shock/Sepsis.. Shock. 2016; 45 (1) : 40-9.|
|Young WA, Fallon EA, Heffernan DS, Efron PA, Cioffi WG, Ayala A Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates.. Surgery. 2016; 161 (5) : 1387-1393.|
|Heffernan DS, Monaghan SF, Ayala A Lymphocyte integrin expression differences between SIRS and sepsis patients.. Irish journal of medical science. 2016;|
|Monaghan SF, Chung CS, Chen Y, Lomas-Neira J, Fairbrother WG, Heffernan DS, Cioffi WG, Ayala A Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS).. Journal of translational medicine. 2016; 14 (1) : 312.|
|Biron BM, Ayala A, Lomas-Neira JL Biomarkers for Sepsis: What Is and What Might Be?. Biomarker Insights. 2015; 10 (Suppl 4) : 7-17.|
|Young JS, Monaghan SF, Chung CS, Cioffi WG, Ayala A, Heffernan DS Divergent Invariant Natural Killer T-Cell Response to Sepsis of Abdominal vs. Non-Abdominal Origin in Human Beings. Surgical infections. 2015; 16 (1) : 29-35.|
|Young JS, Heffernan DS, Chung CS, Kettenmann ML, Young WA, Guillen VS, Cioffi WG, Ayala A Effect of PD-1: PD-L1 in Invariant Natural Killer T Cell Emigration and Chemotaxis Following Sepsis.. Shock. 2015; 45 (5) : 534-9.|
|Burga RA, Thorn M, Point GR, Guha P, Nguyen CT, Licata LA, DeMatteo RP, Ayala A, Joseph Espat N, Junghans RP, Katz SC Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T.. Cancer immunology, immunotherapy : CII. 2015;|
|Tang L, Bai J, Chung CS, Lomas-Neira J, Chen Y, Huang X, Ayala A PD-L1 Regulates the Tregs' Capacity to Repress Shock/Sepsis Induced Indirect Lung Injury (iALI) by Recruiting Phosphatase SHP-1.. Shock. 2015; 43 (1) : 47-54.|
|Ottinger ME, Monaghan SF, Gravenstein S, Cioffi WG, Ayala A, Heffernan DS The geriatric cytokine response to trauma: time to consider a new threshold.. Surgical Infections/Surgical infections. 2015; 15 (6) : 800-805.|
|Heffernan DS, Monaghan SF, Chung CS, Cioffi WG, Gravenstein S, Ayala A A divergent response of innate regulatory T-cells to sepsis in humans: circulating invariant natural killer T-cells are preserved.. Human immunology. 2014; 75 (3) : 277-82.|
|Tang, L., Bai, J., Chung, C.-S., Lomas-Neira, J., Chen, Y., Huang, X., Ayala, A. Active players in resolution of shock/sepsis induced indirect lung injury: immunomodulatory effects of Tregs and PD-1.. Journal of Leukocyte Biology. 2014; 96 : 809-920.|
|Ramachandran G, Kaempfer R, Chung CS, Shirvan A, Chahin AB, Palardy JE, Parejo NA, Chen Y, Whitford M, Arad G, Hillman D, Shemesh R, Blackwelder W, Ayala A, Cross AS, Opal SM CD28 homodimer interface mimetic peptide acts as a preventive and therapeutic agent in models of severe bacterial sepsis and Gram-negative bacterial peritonitis.. Journal of Infectious Diseases. 2014; 211 (6) : 809-20.|
|Huang X, Chen Y, Chung CS, Yuan Z, Monaghan SF, Wang F, Ayala A Identification of B7-H1 as a novel mediator of the innate immune/proinflammatory response as well as a possible myeloid cell prognostic biomarker in sepsis.. The Journal of Immunology. 2014; 192 (3) : 1091-9.|
|Lomas-Neira J, Venet F, Chung CS, Thakkar R, Heffernan D, Ayala A Neutrophil-endothelial interactions mediate angiopoietin-2-associated pulmonary endothelial cell dysfunction in indirect acute lung injury in mice.. American Journal of Respiratory Cell and Molecular Biology. 2014; 50 (1) : 193-200.|
|Ayala A, Elphick GF, Kim YS, Huang X, Carreira-Rosario A, Santos SC, Shubin NJ, Chen Y, Reichner J, Chung CS Sepsis-induced potentiation of peritoneal macrophage migration is mitigated by programmed cell death receptor-1 gene deficiency.. Journal of innate immunity. 2014; 6 (3) : 325-38.|
|Bai, J., Tang, L., Loma-Neira, J., Chen, Y., McLeish, K. R., Uriarte, S. M., Chung, C.-S., Ayala, A. TAT-SNAP-23 treatment inhibits the priming of neutrophil functions contributing to shock and/or sepsis-induced extra-pulmonary acute lung injury.. Innate Immunity. 2014; 21 (1) : 42-54.|
|Hutchins NA, Unsinger J, Hotchkiss RS, Ayala A The new normal: immunomodulatory agents against sepsis immune suppression.. Trends in molecular medicine. 2014; 20 (4) : 224-33.|
|Shubin NJ, Monaghan SF, Heffernan DS, Chung CS, Ayala A B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients.. Critical Care. 2013; 17 (6) : R276.|
|Licata LA, Nguyen CT, Burga RA, Falanga V, Espat NJ, Ayala A, Thorn M, Junghans RP, Katz SC Biliary obstruction results in PD-1-dependent liver T cell dysfunction and acute inflammation mediated by Th17 cells and neutrophils.. Journal of Leukocyte Biology. 2013; 94 (4) : 813-23.|
|Heffernan DS, Monaghan SF, Thakkar RK, Tran ML, Chung CS, Gregory SH, Cioffi WG, Ayala A Inflammatory mechanisms in sepsis: elevated invariant natural killer T-cell numbers in mouse and their modulatory effect on macrophage function.. Shock. 2013; 40 (2) : 122-8.|
|Hutchins NA, Wang F, Wang Y, Chung CS, Ayala A Kupffer cells potentiate liver sinusoidal endothelial cell injury in sepsis by ligating programmed cell death ligand-1.. Journal of Leukocyte Biology. 2013; 94 (5) : 963-70.|
|Hutchins NA, Chung CS, Borgerding JN, Ayala CA, Ayala A Kupffer cells protect liver sinusoidal endothelial cells from Fas-dependent apoptosis in sepsis by down-regulating gp130.. The American Journal of Pathology. 2013; 182 (3) : 742-54.|
|Shubin NJ, Chung CS, Heffernan DS, Irwin LR, Monaghan SF, Ayala A BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction.. Journal of Leukocyte Biology. 2012; 92 (3) : 593-603.|
|Perl M, Kieninger M, Huber-Lang MS, Gross HJ, Bachem MG, Braumüller S, Gebhard F, Ayala A, Knöferl MW Divergent effects of activated neutrophils on inflammation, Kupffer cell/splenocyte activation, and lung injury following blunt chest trauma.. Shock. 2012; 37 (2) : 210-8.|
|Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern.. Critical Care. 2012; 16 (1) : R12.|
|Chichger H, Grinnell KL, Casserly B, Chung CS, Braza J, Lomas-Neira J, Ayala A, Rounds S, Klinger JR, Harrington EO Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury.. AJP: Lung Cellular and Molecular Physiology. 2012; 303 (10) : L880-8.|
|Monaghan SF, Thakkar RK, Heffernan DS, Huang X, Chung CS, Lomas-Neira J, Cioffi WG, Ayala A Mechanisms of indirect acute lung injury: a novel role for the coinhibitory receptor, programmed death-1.. Annals of surgery. 2012; 255 (1) : 158-64.|
|Monaghan SF, Thakkar RK, Tran ML, Huang X, Cioffi WG, Ayala A, Heffernan DS Programmed death 1 expression as a marker for immune and physiological dysfunction in the critically ill surgical patient.. Shock. 2012; 38 (2) : 117-22.|
|Perl M, Hohmann C, Denk S, Kellermann P, Lu D, Braumüller S, Bachem MG, Thomas J, Knöferl MW, Ayala A, Gebhard F, Huber-Lang MS Role of activated neutrophils in chest trauma-induced septic acute lung injury.. Shock. 2012; 38 (1) : 98-106.|
|Nacionales DC, Cuenca AG, Ungaro R, Gentile LF, Joiner D, Satoh M, Lomas-Neira J, Ayala A, Bihorac A, Delano MJ, Ang DN, Efron PA The acute immunological response to blood transfusion is influenced by polymicrobial sepsis.. Shock. 2012; 38 (6) : 598-606.|
|Lomas-Neira J, Perl M, Venet F, Chung CS, Ayala A The role and source of tumor necrosis factor-α in hemorrhage-induced priming for septic lung injury.. Shock. 2012; 37 (6) : 611-20.|
|Lomas-Neira JL, Ayala A What's new in Shock, March 2012?. Shock. 2012; 37 (3) : 239-41.|
|Shubin NJ, Monaghan SF, Ayala A Anti-inflammatory mechanisms of sepsis.. Contributions to microbiology. 2011; 17 : 108-24.|
|Newsome CT, Flores E, Ayala A, Gregory S, Reichner JS Improved antimicrobial host defense in mice following poly-(1,6)-β-D-glucopyranosyl-(1,3)-β-D-glucopyranose glucan treatment by a gender-dependent immune mechanism.. Clinical and vaccine immunology : CVI. 2011; 18 (12) : 2043-9.|
|Thakkar RK, Chung CS, Chen Y, Monaghan SF, Lomas-Neira J, Heffernan DS, Cioffi WG, Ayala A Local tissue expression of the cell death ligand, fas ligand, plays a central role in the development of extrapulmonary acute lung injury.. Shock. 2011; 36 (2) : 138-43.|
|Perl M, Lomas-Neira J, Venet F, Chung CS, Ayala A Pathogenesis of indirect (secondary) acute lung injury.. Expert review of respiratory medicine. 2011; 5 (1) : 115-26.|
|Guan YJ, Zhang Z, Yu C, Ma L, Hu W, Xu L, Gao JS, Chung CS, Wang L, Yang ZF, Fast LD, Chung AS, Kim M, Ayala A, Zhuang S, Zheng S, Chin YE Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation for T cell activation and migration.. The Journal of Immunology. 2011; 187 (3) : 1289-97.|
|Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, Malcus C, Chéron A, Allaouchiche B, Gueyffier F, Ayala A, Monneret G, Venet F Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients.. Critical Care. 2011; 15 (2) : R99.|
|McNeal SI, LeGolvan MP, Chung CS, Ayala A The dual functions of receptor interacting protein 1 in fas-induced hepatocyte death during sepsis.. Shock. 2011; 35 (5) : 499-505.|
|Chung CS, Venet F, Chen Y, Jones LN, Wilson DC, Ayala CA, Ayala A Deficiency of Bid protein reduces sepsis-induced apoptosis and inflammation, while improving septic survival.. Shock. 2010; 34 (2) : 150-61.|
|Wang P, Varghese AJ, Ayala A, Wang D, Quinn MA Editorial board 2010.. International journal of clinical and experimental medicine. 2010; 3 (4) : 347-9.|
|Venet F, Huang X, Chung CS, Chen Y, Ayala A Plasmacytoid dendritic cells control lung inflammation and monocyte recruitment in indirect acute lung injury in mice.. The American Journal of Pathology. 2010; 176 (2) : 764-73.|
|Perl M, Chung CS, Perl U, Thakkar R, Lomas-Neira J, Ayala A Therapeutic accessibility of caspase-mediated cell death as a key pathomechanism in indirect acute lung injury.. Critical care medicine. 2010; 38 (4) : 1179-86.|
|Stromberg PE, Woolsey CA, Clark AT, Clark JA, Turnbull IR, McConnell KW, Chang KC, Chung CS, Ayala A, Buchman TG, Hotchkiss RS, Coopersmith CM CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.. The FASEB Journal. 2009; 23 (6) : 1817-25.|
|Fritzell JA Jr, Mao Q, Gundavarapu S, Pasquariello T, Aliotta JM, Ayala A, Padbury JF, De Paepe ME Fate and effects of adult bone marrow cells in lungs of normoxic and hyperoxic newborn mice.. American Journal of Respiratory Cell and Molecular Biology. 2009; 40 (5) : 575-87.|
|Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohé J, Lepape A, Ayala A, Monneret G Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients.. Intensive care medicine. 2009; 35 (4) : 678-86.|
|Venet F, Chung CS, Huang X, Lomas-Neira J, Chen Y, Ayala A Lymphocytes in the development of lung inflammation: a role for regulatory CD4+ T cells in indirect pulmonary lung injury.. The Journal of Immunology. 2009; 183 (5) : 3472-80.|
|Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, Swan R, Kherouf H, Monneret G, Chung CS, Ayala A PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis.. Proceedings of the National Academy of Sciences. 2009; 106 (15) : 6303-8.|
|Elphick GF, Sarangi PP, Hyun YM, Hollenbaugh JA, Ayala A, Biffl WL, Chung HL, Rezaie AR, McGrath JL, Topham DJ, Reichner JS, Kim M Recombinant human activated protein C inhibits integrin-mediated neutrophil migration.. Blood. 2009; 113 (17) : 4078-85.|
|Hu CK, Venet F, Heffernan DS, Wang YL, Horner B, Huang X, Chung CS, Gregory SH, Ayala A The role of hepatic invariant NKT cells in systemic/local inflammation and mortality during polymicrobial septic shock.. The Journal of Immunology. 2009; 182 (4) : 2467-75.|
|Ayala A, Perl M, Venet F, Lomas-Neira J, Swan R, Chung CS Apoptosis in sepsis: mechanisms, clinical impact and potential therapeutic targets.. Current pharmaceutical design. 2008; 14 (19) : 1853-9.|
|Perl M, Lomas-Neira J, Chung CS, Ayala A Epithelial cell apoptosis and neutrophil recruitment in acute lung injury-a unifying hypothesis? What we have learned from small interfering RNAs.. Molecular medicine (Cambridge, Mass.). 2008; 14 (7-8) : 465-75.|
|Wesche-Soldato DE, Lomas-Neira J, Perl M, Chung CS, Ayala A Hydrodynamic delivery of siRNA in a mouse model of sepsis.. Methods in Molecular Biology. 2008; 442 : 67-73.|
|Venet F, Chung CS, Monneret G, Huang X, Horner B, Garber M, Ayala A Regulatory T cell populations in sepsis and trauma.. Journal of Leukocyte Biology. 2008; 83 (3) : 523-35.|
|Lomas-Neira J, Chung CS, Ayala A RNA interference as a potential therapeutic treatment for inflammation associated lung injury.. International journal of clinical and experimental medicine. 2008; 1 (2) : 154-60.|
|Ward NS, Casserly B, Ayala A The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.. Clinics in chest medicine. 2008; 29 (4) : 617-25, viii.|
|Wang P, Ayala A, Wang D The launch of the international journal of clinical and experimental medicine.. International journal of clinical and experimental medicine. 2008; 1 (1) : 1.|
|Perl M, Chung CS, Perl U, Biffl WL, Cioffi WG, Ayala A Beneficial versus detrimental effects of neutrophils are determined by the nature of the insult.. Journal of the American College of Surgeons. 2007; 204 (5) : 840-52; discussion 852-3.|
|Ayala A, Wesche-Soldato DE, Perl M, Lomas-Neira JL, Swan R, Chung CS Blockade of apoptosis as a rational therapeutic strategy for the treatment of sepsis.. Novartis Foundation symposium. 2007; 280 : 37-49; discussion 49-52, 160-4.|
|Wesche-Soldato DE, Chung CS, Gregory SH, Salazar-Mather TP, Ayala CA, Ayala A CD8+ T cells promote inflammation and apoptosis in the liver after sepsis: role of Fas-FasL.. The American Journal of Pathology. 2007; 171 (1) : 87-96.|
|Huang X, Venet F, Chung CS, Lomas-Neira J, Ayala A Changes in dendritic cell function in the immune response to sepsis. Cell- & tissue-based therapy.. Expert opinion on biological therapy. 2007; 7 (7) : 929-38.|
|Lomas-Neira JL, Ayala A CXCL2 polymorphism in sepsis and acute respiratory distress syndrome: pathological significance lost in translation.. Critical care medicine. 2007; 35 (10) : 2439-40.|
|Venet F, Tissot S, Debard AL, Faudot C, Crampé C, Pachot A, Ayala A, Monneret G Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock.. Critical care medicine. 2007; 35 (8) : 1910-7.|
|Perl M, Chung CS, Perl U, Lomas-Neira J, de Paepe M, Cioffi WG, Ayala A Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury.. Am J Respir Crit Care Med. 2007; 176 (6) : 591-601.|
|Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, O'Malley KA, Wynn JL, Antonenko S, Al-Quran SZ, Swan R, Chung CS, Atkinson MA, Ramphal R, Gabrilovich DI, Reeves WH, Ayala A, Phillips J, Laface D, Heyworth PG, Clare-Salzler M, Moldawer LL MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis.. Journal of Experimental Medicine. 2007; 204 (6) : 1463-74.|
|Swan R, Chung CS, Albina J, Cioffi W, Perl M, Ayala A Polymicrobial sepsis enhances clearance of apoptotic immune cells by splenic macrophages.. Surgery. 2007; 142 (2) : 253-61.|
|Chung CS, Chen Y, Grutkoski PS, Doughty L, Ayala A SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis.. Apoptosis : an international journal on programmed cell death. 2007; 12 (7) : 1143-53.|
|Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A The apoptotic pathway as a therapeutic target in sepsis.. Current drug targets. 2007; 8 (4) : 493-500.|
|Wisnoski N, Chung CS, Chen Y, Huang X, Ayala A The contribution of CD4+ CD25+ T-regulatory-cells to immune suppression in sepsis.. Shock. 2007; 27 (3) : 251-7.|
|Scumpia PO, Delano MJ, Kelly-Scumpia KM, Weinstein JS, Wynn JL, Winfield RD, Xia C, Chung CS, Ayala A, Atkinson MA, Reeves WH, Clare-Salzler MJ, Moldawer LL Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis.. Blood. 2007; 110 (10) : 3673-81.|
|Doughty LA, Carlton S, Galen B, Cooma-Ramberan I, Chung CS, Ayala A Activation of common antiviral pathways can potentiate inflammatory responses to septic shock.. Shock. 2006; 26 (2) : 187-94.|
|Perl M, Chung CS, Garber M, Huang X, Ayala A Contribution of anti-inflammatory/immune suppressive processes to the pathology of sepsis.. Frontiers in Bioscience. 2006; 11 : 272-99.|
|Chung CS, Watkins L, Funches A, Lomas-Neira J, Cioffi WG, Ayala A Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.. American journal of physiology. Regulatory, integrative and comparative physiology. 2006; 291 (5) : R1338-43.|
|Ayala A, Wesche-Soldato DE, Garber M, Swan R, Perl M No good deed goes unpunished!. Intensive care medicine. 2006; 32 (5) : 637-8.|
|Lomas-Neira J, Chung CS, Perl M, Gregory S, Biffl W, Ayala A Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge.. AJP: Lung Cellular and Molecular Physiology. 2006; 290 (1) : L51-8.|
|Perl M, Chung CS, Ayala A Apoptosis.. Critical care medicine. 2005; 33 (12 Suppl) : S526-9.|
|Lomas-Neira J, Chung CS, Grutkoski PS, Dunican A, Simms HH, Cioffi WG, Ayala A Divergent roles of murine neutrophil chemokines in hemorrhage induced priming for acute lung injury.. Cytokine. 2005; 31 (3) : 169-79.|
|Wesche-Soldato DE, Chung CS, Lomas-Neira J, Doughty LA, Gregory SH, Ayala A In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice.. Blood. 2005; 106 (7) : 2295-301.|
|Lomas-Neira JL, Chung CS, Wesche DE, Perl M, Ayala A In vivo gene silencing (with siRNA) of pulmonary expression of MIP-2 versus KC results in divergent effects on hemorrhage-induced, neutrophil-mediated septic acute lung injury.. Journal of Leukocyte Biology. 2005; 77 (6) : 846-53.|
|Wesche DE, Lomas-Neira JL, Perl M, Chung CS, Ayala A Leukocyte apoptosis and its significance in sepsis and shock.. Journal of Leukocyte Biology. 2005; 78 (2) : 325-37.|
|Song GY, Chung CS, Rhee RJ, Cioffi WG, Ayala A Loss of signal transducer and activator of transduction 4 or 6 signaling contributes to immune cell morbidity and mortality in sepsis.. Intensive care medicine. 2005; 31 (11) : 1564-9.|
|Lomas-Neira J, Ayala A Pepducins: an effective means to inhibit GPCR signaling by neutrophils.. Trends in Immunology. 2005; 26 (12) : 619-21.|
|Perl M, Gebhard F, Brückner UB, Ayala A, Braumüller S, Büttner C, Kinzl L, Knöferl MW Pulmonary contusion causes impairment of macrophage and lymphocyte immune functions and increases mortality associated with a subsequent septic challenge.. Critical care medicine. 2005; 33 (6) : 1351-8.|
|Lomas-Niera, J L, Perl, Mario, Chung, Chun-Shiang, Ayala, Alfred SHOCK AND HEMORRHAGE: AN OVERVIEW OF ANIMAL MODELS. Shock. 2005; 24 (Supplement 1) : 33-39.|
|Lomas-Niera JL, Perl M, Chung CS, Ayala A Shock and hemorrhage: an overview of animal models.. Shock. 2005; 24 Suppl 1 : 33-9.|
|Perl M, Chung CS, Lomas-Neira J, Rachel TM, Biffl WL, Cioffi WG, Ayala A Silencing of Fas, but not caspase-8, in lung epithelial cells ameliorates pulmonary apoptosis, inflammation, and neutrophil influx after hemorrhagic shock and sepsis.. The American Journal of Pathology. 2005; 167 (6) : 1545-59.|
|Wesche-Soldato, D. E., Lomas-Neira, J. L., Perl, M., Jones, L., Chung, C.-S., Ayala, A. The role and regulation of apoptosis in sepsis. Journal of Endotoxin Research. 2005; 11 (6) : 375-382.|
|Wesche-Soldato DE, Lomas-Neira JL, Perl M, Jones L, Chung CS, Ayala A The role and regulation of apoptosis in sepsis.. Journal of Endotoxin Research. 2005; 11 (6) : 375-82.|
|Lomas-Neira JL, Chung CS, Grutkoski PS, Miller EJ, Ayala A CXCR2 inhibition suppresses hemorrhage-induced priming for acute lung injury in mice.. Journal of Leukocyte Biology. 2004; 76 (1) : 58-64.|
|Ding Y, Chung CS, Newton S, Chen Y, Carlton S, Albina JE, Ayala A Polymicrobial sepsis induces divergent effects on splenic and peritoneal dendritic cell function in mice.. Shock. 2004; 22 (2) : 137-44.|
|Grutkoski, Patricia S., Chen, Yaping, Chung, Chun-Shiang, Cioffi, William G., Ayala, Alfred Putative Mechanism of Hemorrhage-Induced Leukocyte Hyporesponsiveness: Induction of Suppressor of Cytokine Signaling-3. The Journal of trauma. 2004; 56 (4) : 742-748.|
|Grutkoski PS, Chen Y, Chung CS, Cioffi WG, Ayala A Putative mechanism of hemorrhage-induced leukocyte hyporesponsiveness: induction of suppressor of cytokine signaling-3.. The Journal of trauma. 2004; 56 (4) : 742-7; discussion 747-8.|
|Newton S, Ding Y, Chung CS, Chen Y, Lomas-Neira JL, Ayala A Sepsis-induced changes in macrophage co-stimulatory molecule expression: CD86 as a regulator of anti-inflammatory IL-10 response.. Surgical infections. 2004; 5 (4) : 375-83.|
|Lomas JL, Chung CS, Grutkoski PS, LeBlanc BW, Lavigne L, Reichner J, Gregory SH, Doughty LA, Cioffi WG, Ayala A Differential effects of macrophage inflammatory chemokine-2 and keratinocyte-derived chemokine on hemorrhage-induced neutrophil priming for lung inflammation: assessment by adoptive cells transfer in mice.. Shock. 2003; 19 (4) : 358-65.|
|Ayala A, Lomas JL, Grutkoski PS, Chung S Fas-ligand mediated apoptosis in severe sepsis and shock.. Scandinavian journal of infectious diseases. 2003; 35 (9) : 593-600.|
|Rhee RJ, Carlton S, Lomas JL, Lane C, Brossay L, Cioffi WG, Ayala A Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction.. Journal of Surgical Research. 2003; 115 (1) : 74-81.|
|Chung CS, Song GY, Lomas J, Simms HH, Chaudry IH, Ayala A Inhibition of Fas/Fas ligand signaling improves septic survival: differential effects on macrophage apoptotic and functional capacity.. Journal of Leukocyte Biology. 2003; 74 (3) : 344-51.|
|Ayala A, Chung CS, Grutkoski PS, Song GY Mechanisms of immune resolution.. Critical care medicine. 2003; 31 (8 Suppl) : S558-71.|
|Meldrum DR, Partrick DA, Cleveland JC Jr, Shenkar R, Meldrum KK, Raiesdana A, Ayala A, Brown JW, Harken AH On-pump coronary artery bypass surgery activates human myocardial NF-kappaB and increases TNF-alpha in the heart.. Journal of Surgical Research. 2003; 112 (2) : 175-9.|
|Ayala A, Lomas JL, Grutkoski PS, Chung CS Pathological aspects of apoptosis in severe sepsis and shock?. The International Journal of Biochemistry & Cell Biology. 2003; 35 (1) : 7-15.|
|Grutkoski PS, Chen Y, Chung CS, Ayala A Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes.. Journal of Leukocyte Biology. 2003; 74 (5) : 916-22.|
|Angele MK, Nitsch S, Knoferl MW, Ayala A, Angele P, Schildberg FW, Jauch KW, Chaudry IH Sex-specific p38 MAP kinase activation following trauma-hemorrhage: involvement of testosterone and estradiol.. AJP: Endocrinology and Metabolism. 2003; 285 (1) : E189-96.|
|Ayala A An immune perspective on selective decontamination of the digestive tract.. Critical care medicine. 2002; 30 (6) : 1397-8.|
|Schwacha MG, Chung CS, Ayala A, Bland KI, Chaudry IH Cyclooxygenase 2-mediated suppression of macrophage interleukin-12 production after thermal injury.. AJP: Cell Physiology. 2002; 282 (2) : C263-70.|
|Yang S, Chung CS, Ayala A, Chaudry IH, Wang P Differential alterations in cardiovascular responses during the progression of polymicrobial sepsis in the mouse.. Shock. 2002; 17 (1) : 55-60.|
|Knöferl MW, Angele MK, Diodato MD, Schwacha MG, Ayala A, Cioffi WG, Bland KI, Chaudry IH Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis.. Annals of surgery. 2002; 235 (1) : 105-12.|
|Song GY, Chung CS, Jarrar D, Cioffi WG, Ayala A Mechanism of immune dysfunction in sepsis: inducible nitric oxide-meditated alterations in p38 MAPK activation.. The Journal of trauma. 2002; 53 (2) : 276-82; discussion 282-3.|
|Joshi AR, Chung CS, Song GY, Lomas J, Priester RA, Ayala A NF-kappaB activation has tissue-specific effects on immune cell apoptosis during polymicrobial sepsis.. Shock. 2002; 18 (4) : 380-6.|
|Grutkoski PS, Graeber CT, Ayala A, Simms HH Paracrine suppression of apoptosis by cytokine-stimulated neutrophils involves divergent regulation of NF-kappaB, Bcl-X(L), and Bak.. Shock. 2002; 17 (1) : 47-54.|
|Ayala A, Chung CS, Lomas JL, Song GY, Doughty LA, Gregory SH, Cioffi WG, LeBlanc BW, Reichner J, Simms HH, Grutkoski PS Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency.. The American Journal of Pathology. 2002; 161 (6) : 2283-94.|
|Grutkoski PS, D'Amico R, Ayala A, Simms HH Tumor necrosis factor-alpha-stimulated polymorphonuclear leukocytes suppress migration and bactericidal activity of polymorphonuclear leukocytes in a paracrine manner.. Critical care medicine. 2002; 30 (3) : 591-7.|
|Knöferl MW, Jarrar D, Angele MK, Ayala A, Schwacha MG, Bland KI, Chaudry IH 17 beta-Estradiol normalizes immune responses in ovariectomized females after trauma-hemorrhage.. AJP: Cell Physiology. 2001; 281 (4) : C1131-8.|
|Song GY, Chung CS, Jarrar D, Chaudry IH, Ayala A Evolution of an immune suppressive macrophage phenotype as a product of P38 MAPK activation in polymicrobial sepsis.. Shock. 2001; 15 (1) : 42-8.|
|Ayala A, Chung CS, Song GY, Chaudry IH IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis.. Cytokine. 2001; 14 (1) : 37-48.|
|Chung CS, Wang W, Chaudry IH, Ayala A Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated.. American journal of physiology. Gastrointestinal and liver physiology. 2001; 280 (5) : G812-8.|
|Chung CS, Yang S, Song GY, Lomas J, Wang P, Simms HH, Chaudry IH, Ayala A Inhibition of Fas signaling prevents hepatic injury and improves organ blood flow during sepsis.. Surgery. 2001; 130 (2) : 339-45.|
|Song GY, Chung CS, Chaudry IH, Ayala A MAPK p38 antagonism as a novel method of inhibiting lymphoid immune suppression in polymicrobial sepsis.. AJP: Cell Physiology. 2001; 281 (2) : C662-9.|
|Dunican AL, Leuenroth SJ, Ayala A, Simms HH CXC chemokine suppression of polymorphonuclear leukocytes apoptosis and preservation of function is oxidative stress independent.. Shock. 2000; 13 (3) : 244-50.|
|Knöferl MW, Diodato MD, Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage?. Archives of surgery (Chicago, Ill. : 1960). 2000; 135 (4) : 425-33.|
|Angele MK, Schwacha MG, Ayala A, Chaudry IH Effect of gender and sex hormones on immune responses following shock.. Shock. 2000; 14 (2) : 81-90.|
|Wichmann MW, Zellweger R, Ayala A, Chaudry IH Effect of naloxone on immune responses after hemorrhagic shock.. Critical care medicine. 2000; 28 (1) : 184-9.|
|Song GY, Chung CS, Chaudry IH, Ayala A IL-4-induced activation of the Stat6 pathway contributes to the suppression of cell-mediated immunity and death in sepsis.. Surgery. 2000; 128 (2) : 133-8.|
|Ayala A, Song GY, Chung CS, Redmond KM, Chaudry IH Immune depression in polymicrobial sepsis: the role of necrotic (injured) tissue and endotoxin.. Critical care medicine. 2000; 28 (8) : 2949-55.|
|Kahlke V, Angele MK, Ayala A, Schwacha MG, Cioffi WG, Bland KI, Chaudry IH Immune dysfunction following trauma-haemorrhage: influence of gender and age.. Cytokine. 2000; 12 (1) : 69-77.|
|Song GY, Chung CS, Chaudry IH, Ayala A Immune suppression in polymicrobial sepsis: differential regulation of Th1 and Th2 responses by p38 MAPK.. Journal of Surgical Research. 2000; 91 (2) : 141-6.|
|Knöferl MW, Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH Insight into the mechanism by which metoclopramide improves immune functions after trauma-hemorrhage.. AJP: Cell Physiology. 2000; 279 (1) : C72-80.|
|Schwacha MG, Ayala A, Chaudry IH Insights into the role of gammadelta T lymphocytes in the immunopathogenic response to thermal injury.. Journal of Leukocyte Biology. 2000; 67 (5) : 644-50.|
|Angele MK, Fitzal F, Smail N, Knöferl MW, Schwacha MG, Ayala A, Wang P, Chaudry IH L-arginine attenuates trauma-hemorrhage-induced liver injury.. Critical care medicine. 2000; 28 (9) : 3242-8.|
|Chung CS, Song GY, Moldawer LL, Chaudry IH, Ayala A Neither Fas ligand nor endotoxin is responsible for inducible peritoneal phagocyte apoptosis during sepsis/peritonitis.. Journal of Surgical Research. 2000; 91 (2) : 147-53.|
|Dunican A, Grutkoski P, Leuenroth S, Ayala A, Simms HH Neutrophils regulate their own apoptosis via preservation of CXC receptors.. Journal of Surgical Research. 2000; 90 (1) : 32-8.|
|Kahlke V, Angele MK, Schwacha MG, Ayala A, Cioffi WG, Bland KI, Chaudry IH Reversal of sexual dimorphism in splenic T lymphocyte responses after trauma-hemorrhage with aging.. AJP: Cell Physiology. 2000; 278 (3) : C509-16.|
|Chung CS, Song GY, Wang W, Chaudry IH, Ayala A Septic mucosal intraepithelial lymphoid immune suppression: role for nitric oxide not interleukin-10 or transforming growth factor-beta.. The Journal of trauma. 2000; 48 (5) : 807-12; discussion 812-3.|
|Leuenroth SJ, Grutkoski PS, Ayala A, Simms HH Suppression of PMN apoptosis by hypoxia is dependent on Mcl-1 and MAPK activity.. Surgery. 2000; 128 (2) : 171-7.|
|Leuenroth SJ, Grutkoski PS, Ayala A, Simms HH The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis.. Journal of Leukocyte Biology. 2000; 68 (1) : 158-66.|
|Catania RA, Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH Dehydroepiandrosterone restores immune function following trauma-haemorrhage by a direct effect on T lymphocytes.. Cytokine. 1999; 11 (6) : 443-50.|
|Knöferl MW, Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH Do different rates of fluid resuscitation adversely or beneficially influence immune responses after trauma-hemorrhage?. The Journal of trauma. 1999; 46 (1) : 23-33.|
|Ayala A, Xu YX, Chung CS, Chaudry IH Does Fas ligand or endotoxin contribute to thymic apoptosis during polymicrobial sepsis?. Shock. 1999; 11 (3) : 211-7.|
|Angele MK, Xu YX, Ayala A, Schwacha MG, Catania RK, Cioffi WG, Bland KI, Chaudry IH Gender dimorphism in trauma-hemorrhage-induced thymocyte apoptosis.. Shock. 1999; 12 (4) : 316-22.|
|Angele MK, Knöferl MW, Schwacha MG, Ayala A, Bland KI, Cioffi WG, Josephson SL, Chaudry IH Hemorrhage decreases macrophage inflammatory protein 2 and interleukin-6 release: a possible mechanism for increased wound infection.. Annals of surgery. 1999; 229 (5) : 651-60; discussion 660-1.|
|Angele MK, Schwacha MG, Smail N, Catania RA, Ayala A, Cioffi WG, Chaudry IH Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages.. The American journal of physiology. 1999; 276 (2 Pt 1) : C285-90.|
|Ayala A, Chung CS, Xu YX, Evans TA, Redmond KM, Chaudry IH Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin.. Immunology. 1999; 97 (1) : 45-55.|
|Angele MK, Smail N, Knöferl MW, Ayala A, Cioffi WG, Chaudry IH L-Arginine restores splenocyte functions after trauma and hemorrhage potentially by improving splenic blood flow.. The American journal of physiology. 1999; 276 (1 Pt 1) : C145-51.|
|Angele MK, Smail N, Ayala A, Cioffi WG, Bland KI, Chaudry IH L-arginine: a unique amino acid for restoring the depressed macrophage functions after trauma-hemorrhage.. The Journal of trauma. 1999; 46 (1) : 34-41.|
|Schwacha MG, Ayala A, Cioffi WG, Bland KI, Chaudry IH Role of protein kinase C in cyclic AMP-mediated suppression of T-lymphocyte activation following burn injury.. Biochimica et biophysica acta. 1999; 1455 (1) : 45-53.|
|Angele MK, Knöferl MW, Schwacha MG, Ayala A, Cioffi WG, Bland KI, Chaudry IH Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage.. The American journal of physiology. 1999; 277 (1 Pt 1) : C35-42.|
|Song GY, Chung CS, Schwacha MG, Jarrar D, Chaudry IH, Ayala A Splenic immune suppression in sepsis: A role for IL-10-induced changes in P38 MAPK signaling.. Journal of Surgical Research. 1999; 83 (1) : 36-43.|
|Angele MK, Knöferl MW, Ayala A, Albina JE, Cioffi WG, Bland KI, Chaudry IH Trauma-hemorrhage delays wound healing potentially by increasing pro-inflammatory cytokines at the wound site.. Surgery. 1999; 126 (2) : 279-85.|
|Song GY, Chung CS, Chaudry IH, Ayala A What is the role of interleukin 10 in polymicrobial sepsis: anti-inflammatory agent or immunosuppressant?. Surgery. 1999; 126 (2) : 378-83.|
|Angele MK, Catania RA, Ayala A, Cioffi WG, Bland KI, Chaudry IH Dehydroepiandrosterone: an inexpensive steroid hormone that decreases the mortality due to sepsis following trauma-induced hemorrhage.. Archives of surgery (Chicago, Ill. : 1960). 1998; 133 (12) : 1281-8.|
|Ayala A, Evans TA, Chaudry IH Does hepatocellular injury in sepsis involve apoptosis?. Journal of Surgical Research. 1998; 76 (2) : 165-73.|
|Ayala A, Xin Xu Y, Ayala CA, Sonefeld DE, Karr SM, Evans TA, Chaudry IH Increased mucosal B-lymphocyte apoptosis during polymicrobial sepsis is a Fas ligand but not an endotoxin-mediated process.. Blood. 1998; 91 (4) : 1362-72.|
|Chung CS, Xu YX, Wang W, Chaudry IH, Ayala A Is Fas ligand or endotoxin responsible for mucosal lymphocyte apoptosis in sepsis?. Archives of surgery (Chicago, Ill. : 1960). 1998; 133 (11) : 1213-20.|
|Zellweger R, Wichmann MW, Ayala A, Chaudry IH Metoclopramide: a novel and safe immunomodulating agent for restoring the depressed macrophage immune function after hemorrhage.. The Journal of trauma. 1998; 44 (1) : 70-7.|
|Xu YX, Ayala A, Chaudry IH Prolonged immunodepression after trauma and hemorrhagic shock.. The Journal of trauma. 1998; 44 (2) : 335-41.|
|Chung CS, Xu YX, Chaudry IH, Ayala A Sepsis induces increased apoptosis in lamina propria mononuclear cells which is associated with altered cytokine gene expression.. Journal of Surgical Research. 1998; 77 (1) : 63-70.|
|Wichmann MW, Ayala A, Chaudry IH Severe depression of host immune functions following closed-bone fracture, soft-tissue trauma, and hemorrhagic shock.. Critical care medicine. 1998; 26 (8) : 1372-8.|
|Angele MK, Ayala A, Monfils BA, Cioffi WG, Bland KI, Chaudry IH Testosterone and/or low estradiol: normally required but harmful immunologically for males after trauma-hemorrhage.. The Journal of trauma. 1998; 44 (1) : 78-85.|
|Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH Testosterone: the culprit for producing splenocyte immune depression after trauma hemorrhage.. The American journal of physiology. 1998; 274 (6 Pt 1) : C1530-6.|
|Samy TS, Ayala A, Catania RA, Chaudry IH Trauma-hemorrhage activates signal transduction pathways in mouse splenic T cells.. Shock. 1998; 9 (6) : 443-50.|
|Zhu XH, Zellweger R, Wichmann MW, Ayala A, Chaudry IH Effects of prolactin and metoclopramide on macrophage cytokine gene expression in late sepsis.. Cytokine. 1997; 9 (6) : 437-46.|
|Ayala A, Karr SM, Evans TA, Chaudry IH Factors responsible for peritoneal granulocyte apoptosis during sepsis.. Journal of Surgical Research. 1997; 69 (1) : 67-75.|
|Wichmann MW, Angele MK, Ayala A, Cioffi WG, Chaudry IH Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock.. Shock. 1997; 8 (4) : 242-8.|
|Wichmann MW, Ayala A, Chaudry IH Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage.. The American journal of physiology. 1997; 273 (4 Pt 1) : C1335-40.|
|Xu YX, Ayala A, Monfils B, Cioffi WG, Chaudry IH Mechanism of intestinal mucosal immune dysfunction following trauma-hemorrhage: increased apoptosis associated with elevated Fas expression in Peyer's patches.. Journal of Surgical Research. 1997; 70 (1) : 55-60.|
|Ayala A, O'Neill PJ, Uebele SA, Herdon CD, Chaudry IH Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell mediators.. The Journal of trauma. 1997; 42 (5) : 882-8.|
|Angele MK, Wichmann MW, Ayala A, Cioffi WG, Chaudry IH Testosterone receptor blockade after hemorrhage in males. Restoration of the depressed immune functions and improved survival following subsequent sepsis.. Archives of surgery (Chicago, Ill. : 1960). 1997; 132 (11) : 1207-14.|
|Xu YX, Wichmann MW, Ayala A, Cioffi WG, Chaudry IH Trauma-hemorrhage induces increased thymic apoptosis while decreasing IL-3 release and increasing GM-CSF.. Journal of Surgical Research. 1997; 68 (1) : 24-30.|
|Zellweger R, Zhu XH, Wichmann MW, Ayala A, DeMaso CM, Chaudry IH Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis.. The Journal of Immunology. 1996; 157 (12) : 5748-54.|
|Ertel W, Morrison MH, Ayala A, Chaudry IH Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis.. Archives of surgery (Chicago, Ill. : 1960). 1992; 127 (1) : 70-5; discussion 75-6.|
|Ayala A, Perrin MM, Ertel W, Chaudry IH Differential effects of hemorrhage on Kupffer cells: decreased antigen presentation despite increased inflammatory cytokine (IL-1, IL-6 and TNF) release.. Cytokine. 1992; 4 (1) : 66-75.|
|Ayala A, Kisala JM, Felt JA, Perrin MM, Chaudry IH Does endotoxin tolerance prevent the release of inflammatory monokines (interleukin 1, interleukin 6, or tumor necrosis factor) during sepsis?. Archives of surgery (Chicago, Ill. : 1960). 1992; 127 (2) : 191-6; discussion 196-7.|
|Meldrum DR, Ayala A, Perrin MM, Ertel W, Chaudry IH Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage.. Journal of Surgical Research. 1991; 51 (2) : 158-64.|
|Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin.. Cytokine. 1990; 2 (3) : 170-4.|
Research interests include projects looking at: 1) determing how select expression of cell surface co-inhibitory proteins (check-point proteins) and their ligands, on innate immune cells as well as non-immune cells; alter the morbid events associated with adult sepsis. 2) Utilizing a novel model of indirect-acute lung (iALI) to ask how check-point protein expression affects the patho-mechanisms driving iALI. Finally, 3) since the neonate possesses a unique/ naive immune system and is more susceptible to morbid response in the face of infectious challenge,we are examining if the expression of check-point protein family members have a comparative impact on the neonate's response to septic insult.
The work in our laboratory has centered on understanding the patho-physiological effects of shock/ tissue injury/ sepsis that lead to immune dysfunction and subsequent multiple organ failure in the critically ill trauma patient (through animal modeling and collaborative clinical studies). We have described, over the years, numerous deficits in both components of cell-mediated (T-cell, NKT-cell, gd T-cell, Treg-cell, ILC2, etc) and innate (macrophage, neutrophil, dendritic cells) immune responsiveness induced by shock or sepsis, which are underpinned by alterations in cell signaling, protein translation and transcription patterns. Particular emphasis has been directed at defining the role of soluble mediators (e.g., IL-4, IL-10, IL-16, MCP-1, MIP-2/KC/IL-8, TGF-b, PGE2, NO, steroids, etc.), inhibitory receptors (e.g., PD-1:PD-L1/L2, BTLA:HVEM, VISTA, FasL:Fas, etc.) and/or cellular pathways (e.g., p38 MAPKs, STATs, SOCS 1/3, Shp1/2, Rip1/3, NFkB, etc.) involved in orchestrating these changes in mouse models and critically ill patient. We have also found evidence of alterations of the immune cell's apoptotic process, present in these animals and are actively examining the contribution of this pathway. It is our hope that, by understanding the cellular/molecular mechanisms which control these alterations in the traumatized or septic animal/patient, we will improve our ability to treat them.
Major Theme of Research: injury, shock, organ dysfunction, immunology and infection
Laboratory Staff-Contact List (Rev: 6/15/2017):
Eleanor Fallon, M.D.
Armand D. Versaci Res. Scholar/
Bethany Biron-Girard, M.S., Ph.D.
Yaping Chen, B.S.
Sr. Res. Assist.
Courtney V. Coto, A.D. Med. Trans.
Leadership Alliance-Undergrad. Student (NIH-T35 SR-EIP)
Collaborators at Other Institutions:
Linc L. Moldawer, Ph.D.
Laboratory Alumni (back to: 2000):
Whitney Young, M.D.
Lunxian (Kelly) Tang, M.D., M.S.
Maude Kettenman, M.D., M.S.
Fei Wang, M.D., M.S.
Sam McNeal, Ph.D.
Nicholas Shubin, Ph.D.
Jianwen (Jen) Bai, M.D., M.S.
Gabriela Garcia, B.A.
Lydea Irwin, B.S.
Shivana Maharaj, B.A.
Sean Monaghan, M.D.
Eleanor (Ellie) Smith, B.S.
Ye Sul Kim, B.S.
Yvonne Wang, B.S., M.D.
Kim Tran, B.S.
Yu (Tina) Zhao.
Mia Tran, B.S.
Josha Borgerding, B.S.
Rajan Thakkar, M.D.
Sima Patel, B.S.
Nicholas Carter, B.A.
Sadella Santos, B.S.
Fabienne Venet, Ph.D., M.S., Pharm.D.
Arnaldo Carriera, B.S.
Ana Moreno, B.S.
Megan Garber, B.S., M.S.
Earl Campbell, III, B.S.
Brian J. Horner, D.O.
Ryan Swan, M.D.
Doreen Szollosi (maiden name: Wesche-Soldato), Ph.D.
Leia Foster, B.S.
Caroline Hu, B.A., M.S.
Mario Perl, M.D.
Ulrike (Uli) Perl, R.N.
Antonio Funches, B.S.
Tina Rachel, B.A., M.S.
Nicholas Winoski, B.A., M.D.
Ben Galen, B.S., M.D.
Lesley Doughty, M.D.
Rani Cooma-Ramberan, B.S.
Leslie Jones, B.S.
Sarah Newton (maiden name: Bray), B.A., M.D.
Rebecca Rhee, B.A., M.D.
Yanli Ding, D.D.S., Ph.D, D.M.D
Patricia S. Grutkoski, Ph.D.
Crystal Lane, B.S.
Grace Jarrar (maiden name: Song), M.D., B.A.
Watkins, B.A., Ph.D.
Amit R.T. Joshi, M.D., B.A.
Rory A. Priester, M.D., B.A.
Active Grant Support:
NIH-NIGMS Research Grant: "Mechanism of Immune Dysfunction and Morbid Outcome in Response to Shock/Sepsis."
Grant No. 1 R35 GM118097
Principal Investigator: Alfred Ayala
Total Support = $2,960,902 in direct & indirect cost (for 2016-2021).
NIH-NIGMS Research Grant: "Differential Effects of Sepsis on Immune Cell Function."
Grant No. R01 GM046354
Principal Investigator: Alfred Ayala
Total Support = $1,367,400 in direct and indirect cost (for 2013-2017).
NIH-NIGMS Research Grant: "Co-Inhibitory Molecules and the Pathology of Indirect Acute Lung Injury."
Grant No. RO1 GM107149
Principal Investigator: Alfred Ayala
Total Support = $1,208,400 in direct and indirect cost (for 2013-2017).
NIH-NIGMS Administrative Supplement-Equipment Grant: "Differential Effects of Sepsis on Immune Cell Function."
Grant No. R01 GM046354-20S1
Principal Investigator: Alfred Ayala
Total Support = $139,379 in direct and indirect cost (for 2015 only).
Grants/Funding on which 'role' is other than Principle Investigator:
NIH-NIGMS Post-Doctoral Training Grant: "Trauma-inflammation Research Training."
Grant No.: T32-GM08768
Program Director: Jorge E. Albina
Co-Director/Executive Committee/Faculty: Alfred Ayala
Total Support Requested = $1,158,247 in direct and indirect cost (for 2015-2019).
NCRR COBRE Grant: "CardioPulmonary Vascular Biology-COBRE:Endothelial
Cell Injury & Repair."
Grant No. P20-RR032693-01
Program Director: Sharon Rounds
Executive Committee/Mentor (Qing Lu): Alfred Ayala
Total Support = $7,410,000 in direct and indirect cost (for 2013-2019).
NIH-NIHLBI Undergraduate Student Training Grant: "Short-term Training for Minority Students."
Grant No.: T35-HL067704
Principal Investigator: Elizabeth Harrington
Faculty Trainer/Exec. Comm.: Alfred Ayala
Total Support = $229,900 in direct and indirect cost.
NIH-NIGMS Mentored Clinician Scientist Award: "The Role of the Invariant NKT-cell in Hemorrhagic Shock: Regulation of Neutrophil Response."
Grant No.: K08-GM110495
Principle Investigator: Daithi S. Heffernan
Sponsor/Co-Mentor: Alfred Ayala
Total Support Requested = $1,094,124 in direct and indirect cost.
Chun, T.T., Potz, B.A., Young, W.A., Ayala, A. 2017. Chapter 4: Overview of the Molecular Pathways and Mediators of Sepsis. In: “Sepsis: Definitions, Pathophysiology and the Challenge of Bedside Management”; Edited by: Ward, N.S. & Levy, M.M.; Springer, Heidelberg, Germany, pg 47-69.
Monaghan, S.F., Ayala, A. 2016. Part 14.3: Inflammationand the Host Response; Section 311: Adaptive Immunity in Critical Illness. In the “Oxford Textbook of Critical Care, 2nd Edition. Editors: Webb, A., Angus, D., Finfer, S., Gattinoni, L., Singer, M. Oxford University Press, Oxford, UK.
Thakkar, R.K., Huang, X., Lomas-Neira, J., Heffernan, D., Ayala, A. 2011. Chapter 5: Sepsis and the immune response, in: Essential Immunology for Surgeons, Edited by Eremin, O. & Sewell, H., Oxford University Press, Oxford, U.K. pg 303-342.
Chung, C.S., Swan, R., Wesche-Soldato, D.E., Perl, M., Ayala, A. 2009. Apoptosis: in Sepsis and non-infectious SIRS. In: Sepsis and Non-Infectious Systemic Inflammation. Editors: J-M. Cavaillon & C. Adrie. Wiley-VCH, WeinHeim, Germany, pg 205-229.
Wesche-Soldato, D.E., Lomas-Neira, J., Perl, M., Chung, C.S., Ayala, A. 2008. Hydrodynamic Delivery of siRNA in a Mouse Model of Sepsis. Chapter 5 in: Methods in Molecular Biology, volume 442: RNAi: Design and Application. Editors: S. Barik. Human Press Inc., Totowa, NJ, pg 67-73.
Ayala, A., Wesche-Soldato, D.E., Perl, M., Lomas-Neira, J.L., Swan, R., Chung, C.S. 2007. Novartis Foundation Symposium No. 280 on Sepsis-New Insights, New Therapies. Chapter: Blockade of apoptosis as a rational therapeutic strategy for the treatment of sepsis. Wiley Press, Chichester, U.K., pg. 37-52.
Grutkoski, P.S., Chung, C.S., Albina, J.E., Biffl, W.L., Ayala, A. 2004. Chapter: 38. Apoptosis in the Critically Ill. In: Textbook of Critical Care, 5th Edition. Editors: Abraham, E. W.B. Saunders Publishers, Philadelphia, PA, pg. 195-202.
Ayala, A., Chung, C.S., Song, G.Y., Grutkoski, P.S., Simms, H.H. 2002. Chapter 3. Down-Regulation of the Immune Response. In: Molecular & Cellular Biology of Critical Care Medicine. Editors: Linden, P. and Doughty L.A. Kluwer Academic Publishers, Norwell, MA, pg 41-78.
Angele, M.K., Schwacha, M.G., Ayala, A., Chaudry, I.H. 2001. The role of macrophages following hemorrhagic shock. In: Shock, Editors: Z-Y Luo, C-S. Tang, H-M Gin. TianGin Science and Technology Press. TianGin, China. 699-721.
Ayala, A., Wang, P., Chaudry, I.H. 2001. Chapter 27: Shock Models: Hemorrhage. In: Surgical Research. Editors: Souba, W., Wilmore, D. Academic Press, San Diego, CA, pg 317-330.
Chung, C.S., Chaudry, I.H., Ayala, A. 2000. The apoptotic response of the lymphoid immune system to trauma, shock and sepsis. In: Yearbook of Intensive Care and Emergency Medicine-2000. Editors: Vincent, J.L. Springer-Verlag, Heidelberg, Germany pg 27-40.
Ayala, A., Chung, C.S., Song, G.Y. 1999. Lymphocyte anergy, apoptosis and cell activation in polymicrobial sepsis. In: Update in Intensive Care and Emergency Medicine, Vol. 31. Editors: Marshal, J.C., Cohen, J., Vincent, J.L. Springer-Verlag, Berlin, Germany, pg. 226-246.
Angele, M.K., Schwacha, M.G., Ayala, A., Chaudry, I.H. 1999. The immunoinflammatory response to hemorrhage. In: Sepsis and Multiple Organ Dysfunction. Editors: Deitch, E.A., Windsor and J.L. Vincent. Harcourt Brace & Co. Ltd., London, U.K., pg. 117-126.
Ayala, A., Chaudry, I.H. 1998. Anti-cytokine strategies in peritonitis. Is local, intra-abdominal, therapy possible? In: Cytokines and the Abdominal Surgeon, Editor: M. Schein, Medical Intelligence Unit; R.G. Landes Company, Austin, TX. Pg.245-271.
Angele, M.K., Ayala, A., Chaudry, I.H. 1998. Cytokine in experimental peritonitis. In: Cytokines and the Abdominal Surgeon, Editor: M. Schein, Medical Intelligence Unit; R.G. Landes Company, Austin, TX. Pg.107-116.
Zellweger, R., Ayala, A., Chaudry, I.H. 1998. Predisposing factors: effect of sex, nutritional factors and age on the immunity following shock and sepsis. In: Cytokines in Severe Sepsis and Septic Shock. Editors: H. Redl and G. Schlag, Birkhauser Publishing Ltd., Basel, Switzerland, pg. 57-77.
Zellweger, R., Ayala, A., Wang, P., Chaudry, I.H. 1998. Immunomodulation following shock and sepsis. In: Cytokines in Severe Sepsis and Septic Shock. Editors: H. Redl and G. Schlag, Birkhauser Publishing Ltd., Basel, Switzerland, pg. 313-295.
Chaudry, I.H., Wichmann, M.W., Ayala, A. 1997. Immunological alterations following hemorrhagic shock: considerations for resuscitation with blood substitutes. In: Fundamental Principles and Clinical Applications of Red Blood Cell Substitutes, Editors, R. Rabinovici, G. Feuerstein, A.S. Rudolph, Marcel-Dekker, New York, pg.165-188.
Ayala, A., Wang, P., Chaudry, I.H. 1996. Hemorrhage induced alteration in macrophage signal transduction. In Immune Consequences of Trauma, Shock and Sepsis: Mechanisms and Therapeutic Approaches, Editor, E. Faist, Pabst, Berlin 84-98.
Chaudry, I.H., Ayala, A., Wang, P. 1996. Early indicator of hepatocellular dysfunction in sepsis and hemorrhage. In Immune Consequences of Trauma, Shock and Sepsis: Mechanisms and Therapeutic Approaches, Editor, E. Faist, Pabst, Berlin 935-947.
Chaudry, I.H., Wang, P., Ayala, A. 1996. Hepatic and splenic macrophage response to shock. In Immune Consequences of Trauma, Shock and Sepsis: Mechanisms and Therapeutic Approaches, Editor, E. Faist, Pabst, Berlin 130-141.
Chaudry, I.H., Zellweger, R., Ayala, A. 1995. The role of bacterial translocation in kupffer cell immune function following hemorrhage. In Bacterial Endotoxins: Lipopolysaccharides, From Genes to Therapy, Editor, E. Faist, Wiley-Liss, Inc., New York, pg 209-218.
Chaudry, I.H., Ayala, A., Meldrum, D., and W. Ertel. 1993. Hemorrhage-induced alterations in cell-mediated immune function. In Immune Consequences of Trauma, Shock and Sepsis: Mechanisms and Therapeutic Approaches, Editor, E. Faist, Springer-Verlag, Berlin, 149-159.
Stephan, R.N., Ayala, A., Chaudry, I.H. 1993. Monocyte and lymphocyte responses following trauma. In Pathophysiology of Shock, Sepsis and Organ Failure, Editor, G. Schlag and H. Redl, Springer-Verlag, Berlin, 131-139.
BOOK:Chaudry, I.H., Ayala, A. Immunologic Aspects of Hemorrhage." Medical Intelligence Unit; R.G. Landes Company, Austin, TX, October, 1992.
|1985||PhD||Cleveland State University|
|1978||MS||Cleveland State University|
|1976||BS||Bowling Green State University|
Recipient of an NIH-NIGMS - Maximizing Investigators' Research Award-MIRA (2016)
Recipient of the Shock Society's - Distinguished Service Award (2011)
Recipient of the Shock Society's - Scientific Achievement Award (2007)
Surgical Infection Society - Joseph Susman Awarde (1994)
SIS Recorder/Council Member (2005-07)
Society of Leukocyte Biology- Councilor (2011-present) (by appoinment)
Society of Leukocyte Biology- Co-Program Chariman (2013) (by appoinment)
Shock Society- President (2004-05), Treasurer (2002-04), Sci. Program Chair. (2001)
Society of Leukocyte Biology- Councilor (2011-2013) (by appoinment)
|Albina, Jorge||Professor of Surgery|
|Brossay, Laurent||Charles A. and Helen B. Stuart Professor of Medical Science, Professor of Molecular Microbiology and Immunology, Chair of Molecular Microbiology and Immunology|
|Chung, Chun-Shiang||Assistant Professor of Surgery (Research)|
|Cioffi, William||J. Murray Beardsley Professor of Surgery, Professor of Medical Science, Chair of Surgery|
|De Paepe, Monique||Professor of Pathology and Laboratory Medicine|
|Gregory, Stephen||Associate Professor of Medicine (Research)|
|Harrington, Elizabeth||Associate Dean for Graduate and Postdoctoral Studies in the Division of Biology and Medicine, Professor of Medicine (Research)|
|Heffernan, Daithi||Assistant Professor of Surgery|
|Jamieson, Amanda||Assistant Professor of Molecular Microbiology and Immunology|
|Lomas-Neira, Joanne||Assistant Professor of Surgery (Research)|
|Lu, Qing||Associate Professor of Medicine (Research)|
|Monaghan, Sean||Assistant Professor of Surgery|
|Opal, Steven||Professor of Medicine|
|Reichner, Jonathan||Co-Director of the Pathobiology Graduate Program, Professor of Surgery (Research)|
|Rounds, Sharon||Professor of Medicine, Professor of Pathology and Laboratory Medicine|
|Tyrka, Audrey||Professor of Psychiatry and Human Behavior|
|Zhuang, Shougang||Professor of Medicine (Research)|
American Society of Investigative Pathology
American Association for the Advancement of Science
American Association of Immunologists
International Cytokine Society
Michigan Society for Medical Research
Society of Protozoologists
Surgical Infection Society
Society of Critical Care Medicine
Society of Leukocyte Biology
|Research Associate||Michigan State University, surgery||1988-1989||East Lansing, MI|
|Postdoctoral Fellow||Michigan State University, microbiology||1985-1988||East Lansing, MI|
IMSD Training Module-Fall 2017
Crit. Reading Sci. Pubs.
Dir. Res./Grad. Independent Study
Intro. to Pathobiol. Res.-overview lect.
Med. Student Independent Study
Topics in Pathiobiology: Immunopathology
Undergrad. Independent Study