ABOUT THE RESEARCHER

OVERVIEW

Lung transplantation is an accepted therapy for end-stage lung disease; however, its utility is limited by overall long-term survival. Current therapies have not had a major impact on lung allograft survival. Therefore the overall goal of our laboratory is to identify novel therapies for prolonging lung allograft survival. There are three major areas of lung allograft injury which are addressed in the laboratory:

  • The early injury with the development of primary graft dysfunction, which is related to an ischemia-reperfusion injury and the innate immune process
  • The alloimmune response with the development of both acute and chronic rejection
  • The development of transplant-mediated fibrosis resulting in loss of lung allograft function and long-term survival

We have developed the orthotopic mouse lung transplant model to address novel or unique pathways that may improve lung allograft function and survival. We are currently evaluating novel reagents that modify the alloimmune response and the development of transplant mediated fibrosis. In addition, we are currently examining the role of lymphatics in the development of transplant-mediated fibrosis.

BACKGROUND

Gary Visner, DO, is a graduate of the Michigan State University College of Osteopathic Medicine. After a pediatrics residency at Columbus (Ohio) Children's Hospital, he completed a fellowship in pediatric pulmonology at the University of Florida College of Medicine, where he went on to serve as chief of pediatric pulmonology and as director of the pediatric lung transplant program at the university's Shands Teaching Hospital. He has been the medical director of lung transplantation at Boston Children's Hospital since 2008. In addition, he holds the Mary Ellen Beck-Wohl Chair in Pulmonary Medicine at Boston Children's Hospital and is an Associate Professor at Harvard Medical School.

PUBLICATIONS

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  1. miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy. Am J Transplant. 2021 Mar 25. View abstract
  2. Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial. Am J Transplant. 2021 Mar 22. View abstract
  3. N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction. J Heart Lung Transplant. 2021 Mar 02. View abstract
  4. The impact of gastrointestinal dysmotility on the aerodigestive microbiome of pediatric lung transplant recipients. J Heart Lung Transplant. 2021 Mar; 40(3):210-219. View abstract
  5. Pediatric lung transplant: Correlation of pretransplant condition with post-transplant outcomes. Pediatr Transplant. 2021 Mar; 25(2):e13889. View abstract
  6. FK506 induces lung lymphatic endothelial cell senescence and downregulates LYVE-1 expression, with associated decreased hyaluronan uptake. Mol Med. 2020 07 31; 26(1):75. View abstract
  7. When to consider a posterolateral descending aortopexy in addition to a posterior tracheopexy for the surgical treatment of symptomatic tracheobronchomalacia. J Pediatr Surg. 2020 Dec; 55(12):2682-2689. View abstract
  8. Current evaluation and management of plastic bronchitis in the pediatric population. Int J Pediatr Otorhinolaryngol. 2020 Mar; 130:109799. View abstract
  9. Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2020 01 01; 318(1):L78-L88. View abstract
  10. Medical Deferred Action - Living on Borrowed Time. N Engl J Med. 2019 Oct 24; 381(17):1601-1603. View abstract
  11. Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study. Am J Transplant. 2019 12; 19(12):3284-3298. View abstract
  12. Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms. Circulation. 2019 09 09; 140(10):846-863. View abstract
  13. Treatment of severe persistent asthma with IL-6 receptor blockade. J Allergy Clin Immunol Pract. 2019 May - Jun; 7(5):1639-1642.e4. View abstract
  14. Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation. J Heart Lung Transplant. 2019 01; 38(1):92-99. View abstract
  15. Purinergic P2X4 receptors and mitochondrial ATP production regulate T cell migration. J Clin Invest. 2018 08 01; 128(8):3583-3594. View abstract
  16. P2X7R mutation disrupts the NLRP3-mediated Th program and predicts poor cardiac allograft outcomes. J Clin Invest. 2018 08 01; 128(8):3490-3503. View abstract
  17. RNAi-mediated reduction of hepatic Tmprss6 diminishes anemia and secondary iron overload in a splenectomized mouse model of ß-thalassemia intermedia. Am J Hematol. 2018 Jun; 93(6):745-750. View abstract
  18. Descending Aortopexy and Posterior Tracheopexy for Severe Tracheomalacia and Left Mainstem Bronchomalacia. Semin Thorac Cardiovasc Surg. 2019; 31(3):479-485. View abstract
  19. Posterior Tracheopexy for Severe Tracheomalacia Associated with Esophageal Atresia (EA): Primary Treatment at the Time of Initial EA Repair versus Secondary Treatment. Front Surg. 2017; 4:80. View abstract
  20. Anellovirus loads are associated with outcomes in pediatric lung transplantation. Pediatr Transplant. 2018 02; 22(1). View abstract
  21. Risk and outcomes of pulmonary fungal infection after pediatric lung transplantation. Clin Transplant. 2017 Nov; 31(11). View abstract
  22. Lymphatic Vessels: The Next Frontier in Lung Transplant. Ann Am Thorac Soc. 2017 Sep; 14(Supplement_3):S226-S232. View abstract
  23. Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study. Pediatr Transplant. 2017 Sep; 21(6). View abstract
  24. Transplant center volume and outcomes in lung transplantation for cystic fibrosis. Transpl Int. 2017 Apr; 30(4):371-377. View abstract
  25. Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes. J Heart Lung Transplant. 2017 Aug; 36(8):854-861. View abstract
  26. Outcomes of mechanical support in a pediatric lung transplant center. Pediatr Pulmonol. 2017 03; 52(3):360-366. View abstract
  27. Paracorporeal lung assist device in infants and toddlers: Coming of age? Pediatr Transplant. 2016 Mar; 20(2):191-3. View abstract
  28. Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant. Am J Transplant. 2016 Mar; 16(3):930-7. View abstract
  29. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection. J Clin Invest. 2015 Nov 02; 125(11):4255-68. View abstract
  30. Official American Thoracic Society technical standards: flexible airway endoscopy in children. Am J Respir Crit Care Med. 2015 May 01; 191(9):1066-80. View abstract
  31. The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat Med. 2015 Jan; 21(1):47-54. View abstract
  32. Inhibition of the purinergic pathway prolongs mouse lung allograft survival. Am J Respir Cell Mol Biol. 2014 Aug; 51(2):300-10. View abstract
  33. The purinergic system in allotransplantation. Am J Transplant. 2014 Mar; 14(3):507-14. View abstract
  34. Identification of dedifferentiation and redevelopment phases during postpneumonectomy lung growth. . 2013 Oct 15; 305(8):L542-54. View abstract
  35. Endothelial indoleamine 2,3-dioxygenase protects against development of pulmonary hypertension. Am J Respir Crit Care Med. 2013 Aug 15; 188(4):482-91. View abstract
  36. Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7. Circulation. 2013 Jan 29; 127(4):463-75. View abstract
  37. Lung transplantation in children following bone marrow transplantation: a multi-center experience. Pediatr Transplant. 2013 May; 17(3):231-6. View abstract
  38. Inhibitory effects of pirfenidone on dendritic cells and lung allograft rejection. Transplantation. 2012 Jul 27; 94(2):114-22. View abstract
  39. Indoleamine 2,3-dioxygenase and metabolites protect murine lung allografts and impair the calcium mobilization of T cells. Am J Respir Cell Mol Biol. 2012 Oct; 47(4):405-16. View abstract
  40. Induction therapy with antithymocyte globulin before reperfusion. Ann Thorac Surg. 2010 Oct; 90(4):1110-4; discussion 1114-5. View abstract
  41. Neonatal respiratory failure due to a novel mutation in the surfactant protein C gene. J Perinatol. 2010 Feb; 30(2):151-3. View abstract
  42. Minimal acute rejection in pediatric lung transplantation--does it matter? Pediatr Transplant. 2010 Jun; 14(4):534-9. View abstract
  43. Cytomegalovirus immunoglobulin decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation. J Heart Lung Transplant. 2009 Oct; 28(10):1050-6. View abstract
  44. Pirfenidone inhibits T-cell activation, proliferation, cytokine and chemokine production, and host alloresponses. Transplantation. 2009 Aug 15; 88(3):330-8. View abstract
  45. Reduced cytotoxic function of effector CD8+ T cells is responsible for indoleamine 2,3-dioxygenase-dependent immune suppression. J Immunol. 2009 Jul 15; 183(2):1022-31. View abstract
  46. The risk, prevention, and outcome of cytomegalovirus after pediatric lung transplantation. Transplantation. 2009 May 27; 87(10):1541-8. View abstract
  47. Respiratory viral infections within one year after pediatric lung transplant. Transpl Infect Dis. 2009 Aug; 11(4):304-12. View abstract
  48. Increased mortality after pulmonary fungal infection within the first year after pediatric lung transplantation. J Heart Lung Transplant. 2008 Jun; 27(6):655-61. View abstract
  49. Lung transplantation in cystic fibrosis--primum non nocere? N Engl J Med. 2007 Nov 22; 357(21):2186-8. View abstract
  50. Nonviral gene delivery with indoleamine 2,3-dioxygenase targeting pulmonary endothelium protects against ischemia-reperfusion injury. Am J Transplant. 2007 Oct; 7(10):2291-300. View abstract
  51. Applications of Sleeping Beauty transposons for nonviral gene therapy. IUBMB Life. 2007 Jun; 59(6):374-9. View abstract
  52. Posttransplant monitoring of pediatric lung transplant recipients. Curr Opin Pediatr. 2007 Jun; 19(3):321-6. View abstract
  53. American Society of Transplantation executive summary on pediatric lung transplantation. Am J Transplant. 2007 Feb; 7(2):285-92. View abstract
  54. Sleeping Beauty-mediated eNOS gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J. 2006 Dec; 20(14):2594-6. View abstract
  55. Sleeping Beauty-based gene therapy with indoleamine 2,3-dioxygenase inhibits lung allograft fibrosis. FASEB J. 2006 Nov; 20(13):2384-6. View abstract
  56. Bone marrow stem cells as a vehicle for delivery of heme oxygenase-1 gene. Stem Cells Dev. 2006 Feb; 15(1):79-86. View abstract
  57. Heme oxygenase-1 mediates the protective effects of rapamycin in monocrotaline-induced pulmonary hypertension. Lab Invest. 2006 Jan; 86(1):62-71. View abstract
  58. Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft injury. Am J Respir Crit Care Med. 2006 Mar 01; 173(5):566-72. View abstract
  59. Pirfenidone inhibits obliterative airway disease in mouse tracheal allografts. J Heart Lung Transplant. 2005 Oct; 24(10):1577-85. View abstract
  60. Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model. J Thorac Cardiovasc Surg. 2005 Sep; 130(3):852-8. View abstract
  61. Bone marrow-derived stem-cell repopulation contributes minimally to the Type II pneumocyte pool in transplanted human lungs. Transplantation. 2005 Jul 27; 80(2):206-12. View abstract
  62. Pirfenidone inhibits lung allograft fibrosis through L-arginine-arginase pathway. Am J Transplant. 2005 Jun; 5(6):1256-63. View abstract
  63. The use of multiple transbronchial biopsies as the standard approach to evaluate lung allograft rejection. Pediatr Transplant. 2004 Aug; 8(4):322-8. View abstract
  64. Role of transbronchial biopsies in pediatric lung diseases. Chest. 2004 Jul; 126(1):273-80. View abstract
  65. Heme oxygenase-1 expression in human lungs with cystic fibrosis and cytoprotective effects against Pseudomonas aeruginosa in vitro. Am J Respir Crit Care Med. 2004 Sep 15; 170(6):633-40. View abstract
  66. Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation. J Am Coll Surg. 2004 Jun; 198(6):945-52. View abstract
  67. Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis. Transplantation. 2003 Aug 27; 76(4):650-6. View abstract
  68. A cis-acting region regulates oxidized lipid-mediated induction of the human heme oxygenase-1 gene in endothelial cells. Arterioscler Thromb Vasc Biol. 2003 Aug 01; 23(8):1416-22. View abstract
  69. Toxic serum trough concentrations after administration of nebulized tobramycin. Pharmacotherapy. 2003 Apr; 23(4):543-5. View abstract
  70. Rapamycin induces heme oxygenase-1 in human pulmonary vascular cells: implications in the antiproliferative response to rapamycin. Circulation. 2003 Feb 18; 107(6):911-6. View abstract
  71. Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. Free Radic Biol Med. 2003 Jan 01; 34(1):124-33. View abstract
  72. Increased expression of heme oxygenase-1 in human lung transplantation. J Heart Lung Transplant. 2002 Oct; 21(10):1120-6. View abstract
  73. Analysis of early deaths after isolated lung transplantation. Chest. 2001 Jul; 120(1):225-32. View abstract
  74. Geneticin induces endogenous heme oxygenase-1 expression: implication in transfection studies. Anal Biochem. 2001 Feb 15; 289(2):303-5. View abstract
  75. Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-beta in human renal epithelial cells. J Biol Chem. 2000 Dec 29; 275(52):40904-9. View abstract
  76. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am J Physiol Renal Physiol. 2000 May; 278(5):F726-36. View abstract
  77. Transcriptional regulation and structural organization of the human cytosolic phospholipase A(2) gene. . 2000 Apr; 278(4):L649-57. View abstract
  78. Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells. Am J Respir Cell Mol Biol. 1999 Apr; 20(4):797-804. View abstract
  79. Linoleyl hydroperoxide transcriptionally upregulates heme oxygenase-1 gene expression in human renal epithelial and aortic endothelial cells. J Am Soc Nephrol. 1998 Nov; 9(11):1990-7. View abstract
  80. Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial cells. Chest. 1998 Jul; 114(1 Suppl):63S-64S. View abstract
  81. Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial cells. Am J Physiol. 1998 05; 274(5):L854-63. View abstract
  82. Identification of urokinase as a hyperoxia-inducible gene. Mol Genet Metab. 1998 Apr; 63(4):295-301. View abstract
  83. Hyperoxia-responsive proteins in rat pulmonary microvascular endothelial cells. Am J Physiol. 1996 Apr; 270(4 Pt 1):L517-25. View abstract
  84. Effects of vasoactive and inflammatory mediators on endothelin-1 expression in pulmonary endothelial cells. Am J Respir Cell Mol Biol. 1995 May; 12(5):503-12. View abstract
  85. Endothelin-1 expression in myenteric neurons cultured from rat small intestine. Regul Pept. 1995 Jan 26; 55(2):167-77. View abstract
  86. Isolation and maintenance of human pulmonary artery endothelial cells in culture isolated from transplant donors. Am J Physiol. 1994 Oct; 267(4 Pt 1):L406-13. View abstract
  87. Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-gamma, TGF-beta, and IL-10 in murine macrophage cell lines and rat peritoneal macrophages. Biochem Biophys Res Commun. 1994 Apr 15; 200(1):126-34. View abstract
  88. Regulation of endothelin-1 expression in normal and transfected endothelial cells. J Cardiovasc Pharmacol. 1993; 22 Suppl 8:S38-41. View abstract
  89. Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary artery and microvascular endothelial cells. Biochem Biophys Res Commun. 1992 Oct 15; 188(1):453-62. View abstract
  90. Rat copper/zinc superoxide dismutase gene: isolation, characterization, and species comparison. Biochem Biophys Res Commun. 1992 Jul 31; 186(2):936-43. View abstract
  91. Multiple mRNA species generated by alternate polyadenylation from the rat manganese superoxide dismutase gene. Nucleic Acids Res. 1992 Jun 25; 20(12):2985-90. View abstract
  92. Regulation of manganese superoxide dismutase in porcine pulmonary artery endothelial cells. Am J Physiol. 1991 Jun; 260(6 Pt 1):L444-9. View abstract
  93. Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. J Biol Chem. 1990 Feb 15; 265(5):2856-64. View abstract