Positions

Overview

  • Hidetaka Hara (MD, PhD) is Associate Professor of Surgery at the University of Alabama at Birmingham. Dr. Hara obtained his MD from Kawasaki Medical School, Okayama, Japan in 1995, and then completed a general surgery fellowship and PhD at Department of Surgery at Hiroshima University, Japan. During his surgical and research training, he became interested in organ transplantation, particularly in the field of xenotransplantation. He came to the United States in May 2004 to gain further experience in transplant immunology. As a Postdoctoral Associate in Dr. David K.C. Cooper’s laboratory at the Thomas E. Starzl Transplantation Institute (STI), University of Pittsburgh, Dr. Hara performs experimental surgeries in large animal models, including pig-to-non-human-primate heart, kidney, liver and islet transplants; and pig-to-pig spleen, kidney, heart and islet transplants. Dr. Hara also has extensive in vitro research experience, investigating the human-to-pig immune response. Dr. Hara rapidly proved to be a valuable member of the group. He made the decision to dedicate himself full-time to research on organ transplantation, particularly in the field of xenotransplantation. Dr. Hara has recently developed interest in pig corneal xenotransplantation. Dr. Hara has contributed to illuminating how genetic modifications in pigs can protect their organs from human immune responses. He has gained very considerable experience and has made major contributions to the field, and his work is now well-known internationally.
    In view of his productivity and growing reputation, Dr. Hara was steadily promoted through the rank of Research Instructor (in 2007) to his present position of Research Assistant Professor (in 2011) at STI. Since Dr. Cooper has relocated his laboratory to the University of Alabama at Birmingham (UAB) where they plan to take xenotransplantation into the clinic within the next few years, Dr. Hara joined Dr. Cooper at UAB as an Assistant Professor of Surgery (on November, 2016). Dr. Hara was promoted from Assistant Professor to Associate Professor (in 2017) at UAB.

    • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Indicators of impending pig kidney and heart xenograft failure: Relevance to clinical organ xenotransplantation - Review article 2019
    2019 Life-supporting Kidney Xenotransplantation From Genetically Engineered Pigs in Baboons: A Comparison of Two Immunosuppressive Regimens 2019
    2019 Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? Review article 2019
    2019 In Search of the Ideal Valve: Optimizing Genetic Modifications to Prevent Bioprosthetic Degeneration 2019
    2019 Circulating pig-specific DNA as a novel biomarker for monitoring xenograft rejection 2019
    2019 Justification of specific genetic modifications in pigs for clinical organ xenotransplantation 2019
    2019 The complex functioning of the complement system in xenotransplantation 2019
    2019 The “Baby Fae” baboon heart transplant—Potential cause of rejection 2019
    2019 Evidence for the important role of inflammation in xenotransplantation 2019
    2019 Carbohydrate antigen expression and anti-pig antibodies in New World capuchin monkeys: Relevance to studies of xenotransplantation 2019
    2019 Genetically-engineered pigs as sources for clinical red blood cell transfusion: What pathobiological barriers need to be overcome? 2019
    2019 Life-supporting porcine cardiac xenotransplantation: The Munich study 2019
    2019 The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome? 2019
    2019 Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells 2019
    2019 Human CTLA4-Ig therapy can give false-positive anti-pig antibody results in primates after xenotransplantation 2019
    2018 B cell phenotypes in baboons with pig artery patch grafts receiving conventional immunosuppressive therapy 2018
    2018 Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model 2018
    2018 Perspectives on the Optimal Genetically Engineered Pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation 2018
    2018 Serum amyloid a as an indicator of impending xenograft failure: Experimental studies 2018
    2018 An approach to induction of tolerance to pig cardiac xenografts in neonates 2018
    2018 Skin xenotransplantation: Historical review and clinical potential 2018
    2018 Data on B cell phenotypes in baboons with pig artery patch grafts receiving conventional immunosuppressive therapy 2018
    2018 Porcine IL-6, IL-1β, and TNF-α regulate the expression of pro-inflammatory-related genes and tissue factor in human umbilical vein endothelial cells 2018
    2018 Immune Responses of HLA Highly Sensitized and Nonsensitized Patients to Genetically Engineered Pig Cells 2018
    2018 Is sensitization to pig antigens detrimental to subsequent allotransplantation? 2018
    2018 Bringing Home the Bacon: Update on the State of Kidney Xenotransplantation 2018
    2018 The Sda and Cad glycan antigens and their glycosyltransferase, β1,4GalNAcT-II, in xenotransplantation 2018
    2018 Xenotransplantation - The current status and prospects 2018
    2017 Potential Antigens Involved in Delayed Xenograft Rejection in a Ggta1/Cmah Dko Pig-to-Monkey Model 2017
    2017 Low anti-pig antibody levels are key to the success of solid organ xenotransplantation: But is this sufficient? 2017
    2017 An Investigation of Extracellular Histones in Pig-To-Baboon Organ Xenotransplantation 2017
    2017 Altered expression of eNOS, prostacyclin synthase, prostaglandin G/H synthase, and thromboxane synthase in porcine aortic endothelial cells after exposure to human serum—relevance to xenotransplantation 2017
    2017 Angiopoietin-1 and angiopoietin-2 protect porcine iliac endothelial cells from human antibody-mediated complement-dependent cytotoxicity through phosphatidylinositide 3-kinase/AKT pathway activation 2017
    2017 Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans 2017
    2017 The impact of serum incubation time on IgM/IgG binding to porcine aortic endothelial cells 2017
    2017 Controlled delivery of platelet-derived proteins enhances porcine wound healing 2017
    2017 Renal xenotransplantation: experimental progress and clinical prospects 2017
    2017 Human IL-6, IL-17, IL-1β, and TNF-α differently regulate the expression of pro-inflammatory related genes, tissue factor, and swine leukocyte antigen class I in porcine aortic endothelial cells 2017
    2017 Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts 2017
    2017 Therapeutic regulation of systemic inflammation in xenograft recipients 2017
    2017 Transplantation of hepatocytes from genetically engineered pigs into baboons 2017
    2017 Development of retrocorneal membrane following pig-to-monkey penetrating keratoplasty 2017
    2017 Initial study of α1,3-galactosyltransferase gene-knockout/CD46 pig full-thickness corneal xenografts in rhesus monkeys 2017
    2017 Klotho attenuated antibody-mediated porcine endothelial cell activation and injury 2017
    2017 Pig-to-primate islet xenotransplantation: Past, present, and future 2017
    2017 Production of α1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-deficient pigs by CRISPR/Cas9 and handmade cloning 2017
    2016 Effect of Rho-kinase Inhibitor, Y27632, on Porcine Corneal Endothelial Cell Culture, Inflammation and Immune Regulation 2016
    2016 Human antibody recognition of xenogeneic antigens (NeuGc and Gal) on porcine heart valves: could genetically modified pig heart valves reduce structural valve deterioration? 2016
    2016 Circulating organ-specific microRNAs serve as biomarkers in organ-specific diseases: Implications for organ allo- and xeno-transplantation 2016
    2016 Thyroid hormone: relevance to xenotransplantation 2016
    2016 Initial in vitro studies on tissues and cells from GTKO/CD46/NeuGcKO pigs 2016
    2016 The pathobiology of pig-to-primate xenotransplantation: A historical review 2016
    2016 Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs 2016
    2016 Expression of NeuGc on Pig Corneas and Its Potential Significance in Pig Corneal Xenotransplantation 2016
    2015 Current status of corneal xenotransplantation 2015
    2015 In vitro testing of an anti-CD40 monoclonal antibody, clone 2C10, in primates and pigs 2015
    2015 Further evidence for sustained systemic inflammation in xenograft recipients (SIXR) 2015
    2015 Pig kidney graft survival in a baboon for 136 days: Longest life-supporting organ graft survival to date 2015
    2015 Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs 2015
    2015 Characterization of the cellular infiltrate in bioprosthetic heart valves explanted from patients with structural valve deterioration 2015
    2015 Expression of NeuGc on pig heart valves 2015
    2015 Glucose metabolism in pigs expressing human genes under an insulin promoter 2015
    2015 In vitro exposure of pig neonatal isletlike cell clusters to human blood 2015
    2015 Pig-to-baboon heterotopic heart transplantation - Exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens 2015
    2015 Systemic inflammation in xenograft recipients precedes activation of coagulation 2015
    2014 Potential for clinical pancreatic islet xenotransplantation 2014
    2014 Progress in pig-to-non-human primate transplantation models (1998-2013): A comprehensive review of the literature 2014
    2014 The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of xenocorneal transplantation 2014
    2014 A comparison of three methods of decellularization of pig corneas to reduce immunogenicity. 2014
    2014 Are there advantages in the use of specific pathogen-free baboons in pig organ xenotransplantation models? 2014
    2014 Characterization of porcine corneal endothelium for xenotransplantation 2014
    2014 Corneal blindness and xenotransplantation 2014
    2014 Distribution of non-gal antigens in pig cornea: Relevance to corneal xenotransplantation 2014
    2014 Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs 2014
    2014 Pig-to-monkey islet xenotransplantation using multi-transgenic pigs 2014
    2014 Regulation of human platelet aggregation by genetically modified pig endothelial cells and thrombin inhibition 2014
    2013 Technique of endoscopic biopsy of islet allografts transplanted into the gastric submucosal space in pigs 2013
    2013 New concepts of immune modulation in xenotransplantation 2013
    2013 Islet xenotransplantation from genetically engineered pigs 2013
    2013 Minimal effect of bortezomib in reducing anti-pig antibodies in human leukocyte antigen-sensitized patients: A pilot study 2013
    2013 Human dominant-negative class II transactivator transgenic pigs - effect on the human anti-pig T-cell immune response and immune status 2013
    2013 Is there a correlation between anti-pig antibody levels in humans and geographic location during childhood? 2013
    2013 Comparison of proliferative capacity of genetically-engineered pig and human corneal endothelial cells 2013
    2013 The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation 2013
    2012 Clinical islet xenotransplantation: How close are we? 2012
    2012 Anti-gal antibodies in α1,3-galactosyltransferase gene-knockout pigs 2012
    2012 Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation 2012
    2012 Costimulation blockade in pig artery patch xenotransplantation - A simple model to monitor the adaptive immune response in nonhuman primates 2012
    2012 Clinical lung xenotransplantation - What donor genetic modifications may be necessary? 2012
    2012 T-cell-based immunosuppressive therapy inhibits the development of natural antibodies in infant baboons 2012
    2012 Clinical xenotransplantation: The next medical revolution? 2012
    2012 Genetically-engineered pig-to-baboon liver xenotransplantation: Histopathology of xenografts and native organs 2012
    2012 Adipose-derived mesenchymal stromal cells from genetically modified pigs: Immunogenicity and immune modulatory properties 2012
    2012 The effect of Gal expression on pig cells on the human T-cell xenoresponse 2012
    2011 Relative efficiency of porcine and human cytotoxic T-lymphocyte antigen 4 immunoglobulin in inhibiting human CD4 + T-cell responses co-stimulated by porcine and human B7 molecules 2011
    2011 Growth of linear carbon chains inside thin double-wall carbon nanotubes 2011
    2011 Initial in vitro investigation of the human immune response to corneal cells from genetically engineered pigs 2011
    2011 Genetically-modified pig mesenchymal stromal cells: Xenoantigenicity and effect on human T-cell xenoresponses 2011
    2011 Xenotransplantation-the future of corneal transplantation? 2011
    2010 Hepatic function after genetically engineered pig liver transplantation in baboons 2010
    2010 An in vitro model of pig liver xenotransplantation-pig complement is associated with reduced lysis of wild-type and genetically modified pig cells 2010
    2010 Atorvastatin or transgenic expression of TFPI inhibits coagulation initiated by anti-nonGal IgG binding to porcine aortic endothelial cells 2010
    2010 The immunology of corneal xenotransplantation: A review of the literature 2010
    2010 Recipient tissue factor expression is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation 2010
    2010 Genetically Engineered Pigs as a Source for Clinical Red Blood Cell Transfusion 2010
    2010 Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants 2010
    2010 Investigation of potential carbohydrate antigen targets for human and baboon antibodies 2010
    2009 Effect of the αgal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model 2009
    2009 Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets 2009
    2009 Genetically engineered pig red blood cells for clinical transfusion: Initial in vitro studies 2009
    2009 Endoscopic gastric submucosal transplantation of islets (ENDO-STI): Technique and initial results in diabetic pigs 2009
    2009 The innate immune response and activation of coagulation in ±1,3-galactosyltransferase gene-knockout xenograft recipients 2009
    2008 In vitro investigation of pig cells for resistance to human antibody-mediated rejection 2008
    2008 Suppressive efficacy and proliferative capacity of human regulatory t cells in allogeneic and xenogeneic responses 2008
    2008 Atorvastatin down-regulates the primate cellular response to porcine aortic endothelial cells in vitro 2008
    2008 Liver xenografts for the treatment of acute liver failure: Clinical and experimental experience and remaining immunologic barriers 2008
    2008 Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: Implications for translation into clinical practice 2008
    2008 Recent advances in pig-to-human organ and cell transplantation 2008
    2008 Safe induction of diabetes by high-dose streptozotocin in pigs 2008
    2007 Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: Implications for xenotransplantation in infants 2007
    2007 The pig-to-primate immune response: Relevance for xenotransplantation 2007
    2007 Progress in xenotransplantation following the introduction of gene-knockout technology 2007
    2006 Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin: Adverse effects and early responses 2006
    2006 Antibodies directed to pig non-Gal antigens in naïve and sensitized baboons 2006
    2006 Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans 2006
    2006 Erratum: Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal antigens, and their relevance for experimental models (Transplant International (2005) 19, (158)) 2006
    2006 Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal antigens, and their relevance for experimental models 2006
    2005 Preformed antibodies to α1,3-galactosyltransferase gene-knockout (GT-KO) pig cells in humans, baboons, and monkeys: Implications for xenotransplantation 2005
    2005 Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells 2005
    2004 Differential diagnosis between graft-versus-host disease and hemophagocytic syndrome after living-related liver transplantation by mixed lymphocyte reaction assay 2004
    2004 Studies on Eleven Kidney Transplants from Non-Heart-Beating Donors 2004
    2003 Limited engraftment capacity of bone marrow-derived mesenchymal cells in xenogeneic bone marrow transplantation 2003
    2002 The role of mouse stroma in rat haematopoiesis in xenogeneic rat/mouse bone marrow transplantation chimeras 2002

    Research Overview

  • I am interested in transplant immunology, particularly in the field of xenotransplantation. I have contributed to illuminating how genetic modifications in pigs can protect their organs from human immune responses.
    Key Words:
    Xenotransplant Immunology, Corneal xenotransplantation, Pig Red blood cells transfusion, Kidney/islet xenotransplantation, T and B cell tolerance, Antibodies, Inflammation, Innate immune response

    • Teaching Overview

  • I have an established record of excellence in teaching and monitoring. I personally supervised the work of all the research fellows, university students, and technicians who have gained experience in the laboratory at the University of Pittsburgh during the past 13 years. I have proved an excellent mentor, training the postdoctoral fellows and technicians in basic and advanced techniques of immunology, enabling many young members of the laboratory to coauthor manuscripts published by the group (Transplantation. 2008;86:1452-1462, Transfusion. 2009;49:2418-2429. Immunology. 2011;134:386-397, Cornea. 2016;35:105-13). I have given seminars in several centers in the USA, Japan, and China. In addition, I have participated as an invited guest speaker at the International Xenotransplantation Association. Many of my trainees (in Dr. Cooper’s laboratory) have presented at national and international meetings, including being invited as guest speakers. Several of his group’s fellows have received the Young Investigator Award at scientific conferences.
    Teaching experience: All were postdoctoral research fellows or medical or undergraduate students unless otherwise indicated.

    In addition to training more than a dozen postdoctoral fellows in Pittsburgh, I have been invited to two centers in China to help establish similar laboratories. Furthermore, our group continues to collaborate with several departments and companies, both domestic (internal) and international. These collaborative groups include the following groups:
    (i) Edmonton, Canada (Dr. James Shapiro at University of Alberta, Edmonton, Canada) focusing on islet transplantation in the GSMS site in humans as a clinical trial, (ii) Winnipeg, MB, Canada (Dr. Rizwan Manji, University of Manitoba) focusing on pig derived bioprosthetic heart valves, (iii) Palermo, Italy (Dr. Bruno Gridelli, ISMETT) in investigating pig-to-baboon hepatocyte xenotransplantation using a clinically-applicable immunosuppressive regimen, (iv) Moscow, Russia (Dr. Nicoli Bovin) focusing on the role of N-glycolylneuraminic acid (Neu-Gc) as a relevant pig antigen in xenotransplantation, (v) Beijing, China (Tongren Hospital, Drs. Zhiqiang Pan and Xiaojuan Dong) focusing on corneal xenotransplantation in NHPs, (vi) Shenzhen, China (Shenzhen Second Hospital, Drs. Chai, Lisha, Wang, Zhou) focusing on kidney and neonatal islet xenotransplantations in NHPs, (vii) Tulane University and Revivicor, Inc. (Dr. David Ayares) focusing on pig lung scaffold implantation in monkeys, (viii) UPMC (Dr. Martin Wijkstrom) focusing on the comparison of serum anti-pig antibody levels, memory T cells and T cell proliferative response to pig stimulator cells between patients with high and low panel-reactive antibodies, (ix) University of Pittsburgh/McGowan Institute (Dr. Yadong Wang) using bioengineered material sheets for wound repair in a diabetic pig model. My involvement was helping carry out in vivo studies (as an advisor). In addition, Dr. Wang and I (as a Co-PI) have received a NIH grant (RO1) to help cover the expense of these studies.

    In all the above mentioned collaborations I have strongly involved in each as either an active participant or as a teaching/advisor.

    • Full Name

  • Hidetaka Hara