Positions

Overview

  • Dr. Byrne is an accomplished and creative scientist performing research at the international level both in the academia and in industry. He has more than 25 years of industry and academic research experience involving development of new technologies in gene regulation, drug development, immunology, and critical advances in the xenotransplantation field. He pioneered the development of binary gene regulation methods for controlling gene expression in transgenic animals using the Herpes simplex virus VP16 transactivator. This work culminated in an early transgenic mouse patent (Patent #5,221,778) and later development of tetracycline repressor based gene regulation (Patent # 5,917,122). Binary gene regulation is now commonly used in transgenic research.

    As Director of Research and Development at Nextran, Inc., a subsidiary of Baxter International, the team he managed was responsible for developing Gal-specific drugs to modulate the anti-Gal antibody response in nonhuman primates and for developing genetically modified pigs with a targeted mutation in the -galactosyl transferase gene thereby creating a strain of pigs deficient in production of the major xenogeneic antigen. He had broad responsibility for molecular analysis of transgenic pigs and immunological analysis of pig-to-primate cardiac xenotransplantation. Dr. Byrne created a variety of transgenic pigs for xenotransplantation and produced the first transgenic pig line approved for use in an FDA approved clinical trial.

    At Mayo Clinic, he continued his research in xenotransplantation and led the field in using proteomic and genetic screening to define new non-Gal pig antigens that contribute to xenograft rejection. This led to the seminal identification of the SDa blood group as a significant xenogeneic glycan in pig tissue. He was the first in the field to apply modern genome wide scanning methods to the analysis of xenograft rejection.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 A Durable Porcine Pericardial Surgical Bioprosthetic Heart Valve: a Proof of Concept.Journal of Cardiovascular Translational Research2019
    2018 PERVading strategies and infectious risk for clinical xenotransplantation.Xenotransplantation.  25:e12402. 2018
    2018 Does human leukocyte antigens sensitization matter for xenotransplantation?Xenotransplantation.  25:e12411. 2018
    2018 B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen.Xenotransplantation.  25:e12394. 2018
    2017 Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?Journal of Immunology Research.  2017:2534653. 2017
    2015 A pig-to-mouse coronary artery transplantation model for investigating the pathogenicity of anti-pig antibody.Xenotransplantation.  22:458-467. 2015
    2015 Current status of pig heart xenotransplantation.International Journal of Surgery.  23:234-239. 2015
    2015 Recent investigations into pig antigen and anti-pig antibody expression.International Journal of Surgery.  23:223-228. 2015
    2014 Cloning and expression of porcine β1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen.Xenotransplantation.  21:543-554. 2014
    2014 Development of a consensus protocol to quantify primate anti-non-Gal xenoreactive antibodies using pig aortic endothelial cells.Xenotransplantation.  21:555-566. 2014
    2014 First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart valve bioprosthesis (by Naso et al.).Xenotransplantation.  21:11-12. 2014
    2013 Histopathologic insights into the mechanism of anti-non-Gal antibody-mediated pig cardiac xenograft rejection.Xenotransplantation.  20:292-307. 2013
    2013 Gal-knockout bioprostheses exhibit less immune stimulation compared to standard biological heart valves.Journal of Heart Valve Disease.  22:383-390. 2013
    2012 Human CD55 expression blocks hyperacute rejection and restricts complement activation in Gal knockout cardiac xenografts.Transplantation.  93:686-692. 2012
    2012 Cardiac xenotransplantation: progress and challenges.Current Opinion in Organ Transplantation.  17:148-154. 2012
    2011 Reply to the EditorJournal of Thoracic and Cardiovascular Surgery.  142:239. 2011
    2011 Comparison of Gal and non-Gal-mediated cardiac xenograft rejection.Transplantation.  91:968-975. 2011
    2011 Identification of new carbohydrate and membrane protein antigens in cardiac xenotransplantation.Transplantation.  91:287-292. 2011
    2011 Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves.Journal of Thoracic and Cardiovascular Surgery.  141:269-275. 2011
    2011 Changes in cardiac gene expression after pig-to-primate orthotopic xenotransplantation.Xenotransplantation.  18:14-27. 2011
    2011 Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants.Xenotransplantation.  18:6-13. 2011
    2010 Prolonged cardiac allograft survival using iodine 131 after human sodium iodide symporter gene transfer in a rat model.Transplantation Proceedings.  42:1888-1894. 2010
    2010 Rat model in the study of the role of α-gal in heart valve bioprostheses calcificationThe Journal of heart transplantation.  29:912-913. 2010
    2010 Gal knockout pig pericardium: new source of material for heart valve bioprostheses.The Journal of heart transplantation.  29:538-543. 2010
    2008 Proteomic identification of non-Gal antibody targets after pig-to-primate cardiac xenotransplantation.Xenotransplantation.  15:268-276. 2008
    2008 Efficient and durable gene transfer to transplanted heart using adeno-associated virus 9 vector.The Journal of heart transplantation.  27:554-560. 2008
    2008 Expression of complement regulatory proteins in accommodated xenografts induced by anti-alpha-Gal IgG1 in a rat-to-mouse model.American Journal of Transplantation.  8:32-40. 2008
    2008 Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts.European Journal of Cardio-Thoracic Surgery.  33:32-39. 2008
    2007 The utility of right ventricular endomyocardial biopsy for the diagnosis of xenograft rejection after CD46 pig-to-baboon cardiac transplantation.The Journal of heart transplantation.  26:1025-1032. 2007
    2006 Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival.Transplantation.  82:1787-1791. 2006
    2006 T-cell responses during pig-to-primate xenotransplantation.Xenotransplantation.  13:31-40. 2006
    2005 Cardiac xenotransplantation: recent preclinical progress with 3-month median survival.Journal of Thoracic and Cardiovascular Surgery.  130:844-851. 2005
    2005 Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function.American Journal of Transplantation.  5:1011-1020. 2005
    2005 Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival.Xenotransplantation.  12:127-133. 2005
    2004 Cardiac xenotransplantation: progress toward the clinic.Transplantation.  78:1569-1575. 2004
    2004 Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival.Xenotransplantation.  11:436-443. 2004
    2004 Cutting Edge: NK cells mediate IgG1-dependent hyperacute rejection of xenografts.Journal of Immunology.  172:7235-7238. 2004
    2003 Serologic analysis of anti-porcine endogenous retroviruses immune responses in humans after ex vivo transgenic pig liver perfusion.ASAIO Journal.  49:407-416. 2003
    2003 Pig cells that lack the gene for alpha1-3 galactosyltransferase express low levels of the gal antigen.Transplantation.  75:430-436. 2003
    2003 The in vitro and in vivo effects of anti-galactose antibodies on endothelial cell activation and xenograft rejection.Journal of Immunology.  170:1531-1539. 2003
    2003 Skin graft survival in genetically identical cloned pigs.Cloning and Stem Cells.  5:117-121. 2003
    2002 Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha1-3 galactose trisaccharide-polyethylene glycol conjugate.Transplantation.  73:1780-1787. 2002
    2002 Development and characterization of anti-Gal B cell receptor transgenic Gal-/- mice.Transplantation.  73:1549-1557. 2002
    2002 Evaluation of different alpha-Galactosyl glycoconjugates for use in xenotransplantation.Bioconjugate Chemistry.  13:571-581. 2002
    2002 CTLA-41g in combination with anti-CD40L prolongs xenograft survival and inhibits anti-gal ab production in GT-Ko mice.American Journal of Transplantation.  2:41-47. 2002
    2001 The structure of anti-Gal immunoglobulin genes in naïve and stimulated Gal knockout mice.Transplantation.  72:1817-1825. 2001
    2001 Tetracycline-inducible systems for Drosophila.Proceedings of the National Academy of Sciences.  98:10775-10780. 2001
    2001 The effect of anti-alphaGal antibody removal with immunoabsorption and splenectomy on CD46 transgenic kidney xenograft survival.Transplantation Proceedings.  33:721-722. 2001
    2000 The role of anti-Galalpha1-3Gal antibodies in acute vascular rejection and accommodation of xenografts.Transplantation.  70:1667-1674. 2000
    2000 Non-depleting anti-CD4, but not anti-CD8, antibody induces long-term survival of xenogeneic and allogeneic hearts in alpha1,3-galactosyltransferase knockout (GT-Ko) mice.Xenotransplantation.  7:275-283. 2000
    2000 The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants.Journal of Thoracic and Cardiovascular Surgery.  120:29-38. 2000
    2000 Anti-galactose-alpha(1,3) galactose antibody production in alpha1,3-galactosyltransferase gene knockout mice after xeno and allo transplantation.Transplant Immunology.  8:129-137. 2000
    1999 Human complement regulatory proteins protect swine lungs from xenogeneic injury.Annals of Thoracic Surgery.  67:769-775. 1999
    1998 Complement-mediated pulmonary xenograft injury: studies in swine-to-primate orthotopic single lung transplant models.Transplantation.  65:1084-1093. 1998
    1998 The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.Journal of Clinical Investigation.  101:1745-1756. 1998
    1998 Glycosyl phosphatidylinositol anchor.Nephron.  6:148-151. 1998
    1997 Humoral responses to pig-to-baboon cardiac transplantation: implications for the pathogenesis and treatment of acute vascular rejection and for accommodation.Human Immunology.  58:91-105. 1997
    1997 Swine lungs expressing human complement-regulatory proteins are protected against acute pulmonary dysfunction in a human plasma perfusion model.Journal of Thoracic and Cardiovascular Surgery.  113:390-398. 1997
    1997 Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage.Transplantation.  63:149-155. 1997
    1996 Development and analysis of transgenic pigs expressing the human complement regulatory protein CD59 and DAF.Transplantation Proceedings.  28:759. 1996
    1996 Spatial and temporal regulation of a lacZ reporter transgene in a binary transgenic mouse system.Transgenic Research.  5:37-48. 1996
    1995 Protection of xenogeneic cardiac endothelium from human complement by expression of CD59 or DAF in transgenic mice.Transplantation.  60:1149-1156. 1995
    1995 In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium.Science.  269:89-92. 1995
    1995 Transgenic expression of human complement regulatory proteins in mice results in diminished complement deposition during organ xenoperfusion.Transplantation.  59:1177-1182. 1995
    1994 Demonstration of intermembrane transfer of CD59 during coculture of human erythrocytes with porcine and bovine aortic endothelial cells.Transplantation Proceedings.  26:1240. 1994
    1994 Erythroid-specific expression of human CD59 and transfer to vascular endothelial cells.Transplantation Proceedings.  26:1241. 1994
    1994 Expression of complement regulatory factors using heterologous promoters in transgenic mice.Transplantation Proceedings.  26:1242. 1994
    1991 Analysis of regulatory genes using the transgenic mouse system.Biotechnology (Reading, Mass.).  16:135-152. 1991
    1989 Multiplex gene regulation: a two-tiered approach to transgene regulation in transgenic mice.Proceedings of the National Academy of Sciences.  86:5473-5477. 1989
    1988 Spatial patterns in the fruiting bodies of the cellular slime mold Polysphondylium pallidum.Differentiation.  38:73-81. 1988
    1987 Genesis of a spatial pattern in the cellular slime mold Polysphondylium pallidum.Proceedings of the National Academy of Sciences.  84:4140-4144. 1987
    1987 Branching in Polysphondylium whorls: Two-dimensional patterning in a three-dimensional systemDevelopmental Biology.  119:302-304. 1987
    1986 Spatial patterning in Polysphondylium: monoclonal antibodies specific for whorl prepatterns.Developmental Biology.  117:442-455. 1986
    1982 Pattern Formation and Tip Inhibition in the Cellular Slime Mold Polysphondylium pallidumDifferentiation.  23:103-108. 1982
    Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; a new source material for bioprosthetic heart valves.Acta Biomaterialia.  41:204-209.
    Prosthesis Type for Aortic- and Mitral-Valve Replacement.New England Journal of Medicine.  378:776-777.

    Research Overview

  • His current research interests at UCL centre on translational research leveraging the expertise and resources developed for xenotransplantation to advance development of new platforms for improved bioprosthetic devices for treating cardiovascular disease.
  • Education And Training

  • Doctor of Science in Biology / Biological Sciences, Princeton University
  • Full Name

  • Guerard Byrne