Research

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Gary Visner, DO

Gary Visner DO
Program:
Transplant Research Program
Division
Respiratory Diseases Research
Hospital Title:
Medical Director, Lung Transplantation; Mary Ellen Beck-Wohl Chair in Pulmonary Medicine
Academic Title:
Associate Professor of Pediatrics, Harvard Medical School
Research Focus Area:
Lung Transplantation Survival

Research 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.

About Gary Visner

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. Parrish A, Fenchel M, Storch GA, Buller R, Mason S, Williams N, Ikle D, Conrad C, Faro A, Goldfarb S, Hayes D, Melicoff-Portillo E, Schecter M, Visner G, Sweet S, Danziger-Isakov L. Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study. Pediatr Transplant. 2017 Jun 21.
  2. Hayes D, Sweet SC, Benden C, Kopp BT, Goldfarb SB, Visner GA, Mallory GB, Tobias JD, Tumin D. Transplant center volume and outcomes in lung transplantation for cystic fibrosis. Transpl Int. 2017 Apr; 30(4):371-377.
  3. Jamie Dy F, Freiberger D, Liu E, Boyer D, Visner G, Rosen R. Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes. J Heart Lung Transplant. 2017 Aug; 36(8):854-861.
  4. Toprak D, Midyat L, Freiberger D, Boyer D, Fynn-Thompson F, Visner G. Outcomes of mechanical support in a pediatric lung transplant center. Pediatr Pulmonol. 2017 Mar; 52(3):360-366.
  5. Visner GA, Fynn-Thompson F. Paracorporeal lung assist device in infants and toddlers: Coming of age? Pediatr Transplant. 2016 Mar; 20(2):191-3.
  6. Tsuang WM, Chan KM, Skeans MA, Pyke J, Hertz MI, Israni AJ, Robbins-Callahan L, Visner G, Wang X, Wozniak TC, Valapour M. Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant. Am J Transplant. 2016 Mar; 16(3):930-7.
  7. Cui Y, Liu K, Monzon-Medina ME, Padera RF, Wang H, George G, Toprak D, Abdelnour E, D'Agostino E, Goldberg HJ, Perrella MA, Forteza RM, Rosas IO, Visner G, El-Chemaly S. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection. J Clin Invest. 2015 Nov 02; 125(11):4255-68.
  8. Faro A, Wood RE, Schechter MS, Leong AB, Wittkugel E, Abode K, Chmiel JF, Daines C, Davis S, Eber E, Huddleston C, Kilbaugh T, Kurland G, Midulla F, Molter D, Montgomery GS, Retsch-Bogart G, Rutter MJ, Visner G, Walczak SA, Ferkol TW, Michelson PH. Official American Thoracic Society technical standards: flexible airway endoscopy in children. Am J Respir Crit Care Med. 2015 May 01; 191(9):1066-80.
  9. Grozovsky R, Begonja AJ, Liu K, Visner G, Hartwig JH, Falet H, Hoffmeister KM. The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat Med. 2015 Jan; 21(1):47-54.
  10. Liu K, Vergani A, Zhao P, Ben Nasr M, Wu X, Iken K, Jiang D, Su X, Fotino C, Fiorina P, Visner GA. Inhibition of the purinergic pathway prolongs mouse lung allograft survival. Am J Respir Cell Mol Biol. 2014 Aug; 51(2):300-10.
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  12. Vergani A, Tezza S, Fotino C, Visner G, Pileggi A, Chandraker A, Fiorina P. The purinergic system in allotransplantation. Am J Transplant. 2014 Mar; 14(3):507-14.
  13. Kho AT, Liu K, Visner G, Martin T, Boudreault F. Identification of dedifferentiation and redevelopment phases during postpneumonectomy lung growth. Am J Physiol Lung Cell Mol Physiol. 2013 Oct 15; 305(8):L542-54.
  14. Xiao Y, Christou H, Liu L, Visner G, Mitsialis SA, Kourembanas S, Liu H. Endothelial indoleamine 2,3-dioxygenase protects against development of pulmonary hypertension. Am J Respir Crit Care Med. 2013 Aug 15; 188(4):482-91.
  15. Vergani A, Tezza S, D'Addio F, Fotino C, Liu K, Niewczas M, Bassi R, Molano RD, Kleffel S, Petrelli A, Soleti A, Ammirati E, Frigerio M, Visner G, Grassi F, Ferrero ME, Corradi D, Abdi R, Ricordi C, Sayegh MH, Pileggi A, Fiorina P. Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7. Circulation. 2013 Jan 29; 127(4):463-75.
  16. Yousef S, Benden C, Boyer D, Elidemir O, Frischer T, Goldfarb S, Lopez-Mitnik G, Mallory G, Visner G, Westall G, Schecter MG. Lung transplantation in children following bone marrow transplantation: a multi-center experience. Pediatr Transplant. 2013 May; 17(3):231-6.
  17. Bizargity P, Liu K, Wang L, Hancock WW, Visner GA. Inhibitory effects of pirfenidone on dendritic cells and lung allograft rejection. Transplantation. 2012 Jul 27; 94(2):114-22.
  18. Iken K, Liu K, Liu H, Bizargity P, Wang L, Hancock WW, Visner GA. 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.
  19. Goldfarb SB, Gaynor JW, Fuller S, Kreindler J, Montenegro LM, Fynn-Thompson F, Visner G. Induction therapy with antithymocyte globulin before reperfusion. Ann Thorac Surg. 2010 Oct; 90(4):1110-4; discussion 1114-5.
  20. Poterjoy BS, Vibert Y, Sola-Visner M, McGowan J, Visner G, Nogee LM. Neonatal respiratory failure due to a novel mutation in the surfactant protein C gene. J Perinatol. 2010 Feb; 30(2):151-3.
  21. Benden C, Faro A, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Mogayzel PJ, Parakininkas D, Solomon M, Visner G, Sweet SC, Danziger-Isakov LA. Minimal acute rejection in pediatric lung transplantation--does it matter? Pediatr Transplant. 2010 Jun; 14(4):534-9.
  22. Ranganathan K, Worley S, Michaels MG, Arrigan S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Mogayzel PJ, Parakininkas D, Solomon M, Visner G, Sweet SC, Faro A, Danziger-Isakov L. 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.
  23. Visner GA, Liu F, Bizargity P, Liu H, Liu K, Yang J, Wang L, Hancock WW. Pirfenidone inhibits T-cell activation, proliferation, cytokine and chemokine production, and host alloresponses. Transplantation. 2009 Aug 15; 88(3):330-8.
  24. Liu H, Liu L, Liu K, Bizargity P, Hancock WW, Visner GA. 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.
  25. Danziger-Isakov LA, Worley S, Michaels MG, Arrigain S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Mogayzel PJ, Parakininkas D, Solomon M, Visner G, Sweet S, Faro A. The risk, prevention, and outcome of cytomegalovirus after pediatric lung transplantation. Transplantation. 2009 May 27; 87(10):1541-8.
  26. Liu M, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Mogayzel PJ, Parakininkas D, Visner G, Sweet S, Faro A, Michaels M, Danziger-Isakov LA. Respiratory viral infections within one year after pediatric lung transplant. Transpl Infect Dis. 2009 Aug; 11(4):304-12.
  27. Danziger-Isakov LA, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Michaels MG, Michelson P, Mogayzel PJ, Parakininkas D, Solomon M, Visner G, Sweet S, Faro A. Increased mortality after pulmonary fungal infection within the first year after pediatric lung transplantation. J Heart Lung Transplant. 2008 Jun; 27(6):655-61.
  28. Allen J, Visner G. Lung transplantation in cystic fibrosis--primum non nocere? N Engl J Med. 2007 Nov 22; 357(21):2186-8.
  29. Liu H, Liu L, Visner GA. 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.
  30. Liu H, Visner GA. Applications of Sleeping Beauty transposons for nonviral gene therapy. IUBMB Life. 2007 Jun; 59(6):374-9.
  31. Visner GA, Goldfarb SB. Posttransplant monitoring of pediatric lung transplant recipients. Curr Opin Pediatr. 2007 Jun; 19(3):321-6.
  32. Faro A, Mallory GB, Visner GA, Elidemir O, Mogayzel PJ, Danziger-Isakov L, Michaels M, Sweet S, Michelson P, Paranjape S, Conrad C, Waltz DA. American Society of Transplantation executive summary on pediatric lung transplantation. Am J Transplant. 2007 Feb; 7(2):285-92.
  33. Liu L, Liu H, Visner G, Fletcher BS. Sleeping Beauty-mediated eNOS gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J. 2006 Dec; 20(14):2594-6.
  34. Liu H, Liu L, Fletcher BS, Visner GA. Sleeping Beauty-based gene therapy with indoleamine 2,3-dioxygenase inhibits lung allograft fibrosis. FASEB J. 2006 Nov; 20(13):2384-6.
  35. Zhou H, Ramiya VK, Visner GA. Bone marrow stem cells as a vehicle for delivery of heme oxygenase-1 gene. Stem Cells Dev. 2006 Feb; 15(1):79-86.
  36. Zhou H, Liu H, Porvasnik SL, Terada N, Agarwal A, Cheng Y, Visner GA. Heme oxygenase-1 mediates the protective effects of rapamycin in monocrotaline-induced pulmonary hypertension. Lab Invest. 2006 Jan; 86(1):62-71.
  37. Liu H, Liu L, Fletcher BS, Visner GA. 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.
  38. Zhou H, Latham CW, Zander DS, Margolin SB, Visner GA. Pirfenidone inhibits obliterative airway disease in mouse tracheal allografts. J Heart Lung Transplant. 2005 Oct; 24(10):1577-85.
  39. Liu H, Drew P, Cheng Y, Visner GA. Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model. J Thorac Cardiovasc Surg. 2005 Sep; 130(3):852-8.
  40. Zander DS, Baz MA, Cogle CR, Visner GA, Theise ND, Crawford JM. 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.
  41. Liu H, Drew P, Gaugler AC, Cheng Y, Visner GA. Pirfenidone inhibits lung allograft fibrosis through L-arginine-arginase pathway. Am J Transplant. 2005 Jun; 5(6):1256-63.
  42. Faro A, Visner G. The use of multiple transbronchial biopsies as the standard approach to evaluate lung allograft rejection. Pediatr Transplant. 2004 Aug; 8(4):322-8.
  43. Visner GA, Faro A, Zander DS. Role of transbronchial biopsies in pediatric lung diseases. Chest. 2004 Jul; 126(1):273-80.
  44. Zhou H, Lu F, Latham C, Zander DS, Visner GA. 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.
  45. Bonnell MR, Visner GA, Zander DS, Mandalapu S, Kazemfar K, Spears L, Beaver TM. Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation. J Am Coll Surg. 2004 Jun; 198(6):945-52.
  46. Visner GA, Lu F, Zhou H, Latham C, Agarwal A, Zander DS. Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis. Transplantation. 2003 Aug 27; 76(4):650-6.
  47. Hill-Kapturczak N, Voakes C, Garcia J, Visner G, Nick HS, Agarwal A. 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.
  48. Kahler DA, Schowengerdt KO, Fricker FJ, Mansfield M, Visner GA, Faro A. Toxic serum trough concentrations after administration of nebulized tobramycin. Pharmacotherapy. 2003 Apr; 23(4):543-5.
  49. Visner GA, Lu F, Zhou H, Liu J, Kazemfar K, Agarwal A. 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.
  50. Dennery PA, Visner G, Weng Yi, Nguyen X, Lu F, Zander D, Yang G. Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. Free Radic Biol Med. 2003 Jan 01; 34(1):124-33.
  51. Lu F, Zander DS, Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation. J Heart Lung Transplant. 2002 Oct; 21(10):1120-6.
  52. Zander DS, Baz MA, Visner GA, Staples ED, Donnelly WH, Faro A, Scornik JC. Analysis of early deaths after isolated lung transplantation. Chest. 2001 Jul; 120(1):225-32.
  53. Shiraishi F, Visner GA, Nick HS, Agarwal A. Geneticin induces endogenous heme oxygenase-1 expression: implication in transfection studies. Anal Biochem. 2001 Feb 15; 289(2):303-5.
  54. Hill-Kapturczak N, Truong L, Thamilselvan V, Visner GA, Nick HS, Agarwal A. 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.
  55. Shiraishi F, Curtis LM, Truong L, Poss K, Visner GA, Madsen K, Nick HS, Agarwal A. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am J Physiol Renal Physiol. 2000 May; 278(5):F726-36.
  56. Dolan-O'Keefe M, Chow V, Monnier J, Visner GA, Nick HS. Transcriptional regulation and structural organization of the human cytosolic phospholipase A(2) gene. Am J Physiol Lung Cell Mol Physiol. 2000 Apr; 278(4):L649-57.
  57. Fogg S, Agarwal A, Nick HS, Visner GA. 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.
  58. Agarwal A, Shiraishi F, Visner GA, Nick HS. 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.
  59. Golden CG, Nick HS, Visner GA. Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial cells. Chest. 1998 Jul; 114(1 Suppl):63S-64S.
  60. Golden CL, Nick HS, Visner GA. Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial cells. Am J Physiol. 1998 May; 274(5 Pt 1):L854-63.
  61. Juul SE, Nick HS, Visner GA. Identification of urokinase as a hyperoxia-inducible gene. Mol Genet Metab. 1998 Apr; 63(4):295-301.
  62. Visner GA, Fogg S, Nick HS. Hyperoxia-responsive proteins in rat pulmonary microvascular endothelial cells. Am J Physiol. 1996 Apr; 270(4 Pt 1):L517-25.
  63. Golden CL, Kohler JP, Nick HS, Visner GA. 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.
  64. Eaker E, Sallustio J, Kohler J, Visner G. Endothelin-1 expression in myenteric neurons cultured from rat small intestine. Regul Pept. 1995 Jan 26; 55(2):167-77.
  65. Visner GA, Staples ED, Chesrown SE, Block ER, Zander DS, Nick HS. 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.
  66. Chesrown SE, Monnier J, Visner G, Nick HS. 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.
  67. Ryan US, Zhong R, Hayes BA, Visner G, Sauther ML. Regulation of endothelin-1 expression in normal and transfected endothelial cells. J Cardiovasc Pharmacol. 1993; 22 Suppl 8:S38-41.
  68. Visner GA, Chesrown SE, Monnier J, Ryan US, Nick HS. 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.
  69. Hsu JL, Visner GA, Burr IA, Nick HS. Rat copper/zinc superoxide dismutase gene: isolation, characterization, and species comparison. Biochem Biophys Res Commun. 1992 Jul 31; 186(2):936-43.
  70. Hurt J, Hsu JL, Dougall WC, Visner GA, Burr IM, Nick HS. Multiple mRNA species generated by alternate polyadenylation from the rat manganese superoxide dismutase gene. Nucleic Acids Res. 1992 Jun 25; 20(12):2985-90.
  71. Visner GA, Block ER, Burr IM, Nick HS. Regulation of manganese superoxide dismutase in porcine pulmonary artery endothelial cells. Am J Physiol. 1991 Jun; 260(6 Pt 1):L444-9.
  72. Visner GA, Dougall WC, Wilson JM, Burr IA, Nick HS. 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.
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