Research Centers

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Genetic Engineering Laboratory

The Genetic Engineering Laboratory in the Transplantation Biology Research Center (TBRC) focuses on understanding the immune response to porcine xenografts, engineering swine for use as solid organ xenotransplantation donors and developing porcine stem cells for use in large animal models of potential stem cell therapies.

The Genetic Engineering Laboratory in the Transplantation Biology Research Center at Massachusetts General Hospital is dedicated to:

  • Alleviating shortages of solid organs through the development of porcine organs compatible with human transplantation by minimizing species incompatibilities between swine donors and human recipients
  • Developing and testing protocols for clinical xenotransplantation in preclinical animal models.  These protocols are designed to address both species incompatibility as well as the role of immune tolerance in reducing the need for long-term immunosuppressive drug therapy in conjunction with xenotransplantation.

 In addition to studies focusing on issues specific to xenotransplantation, we are working to adapt allograft tolerance protocols being developed in other TBRC laboratories to the specific needs of xenotransplantation.

 

Principal Investigator
Robert J. Hawley, PhD
Senior Investigator/Head, Genetic Engineering Laboratory, TBRC
Assistant Immunologist, Massachusetts General Hospital
Assistant Professor of Surgery, Harvard Medical School
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Research TechnologistAseda Tena

The Genetic Engineering Laboratory leads the following projects:

  • Xenogeneic “Tolerization”: In the near term, studies using human CD47 transgenic swine should determine whether inhibition of host phagocytosis of xenogeneic hematopoietic cells can result in efficient and more durable chimerism as a means of inducing tolerance. Even in the absence of durable chimerism, we are well positioned to determine whether hematopoietic cell transplantation, in the context of appropriate recipient conditioning, can sufficiently attenuate xenogeneic responses such that clinically relevant organ survival in the presence of continuing clinically relevant immune suppression is possible
  • Innate rejection: Our current results in xenogeneic skin grafting suggest that a vigorous innate response is possible in the absence of a demonstrable acquired immune response. To the extent that innate responses are modulated in current transplantation protocols, this modulation is likely a byproduct of measures directed against T cell responses. Xenogeneic skin grafting, as a model, has the potential to allow study of measures specifically targeted against innate responses
  • Genetic engineering, large animal models and stem cells: There is considerable potential for genetically modified swine and swine stem cells to serve as animal models in circumstances where murine models are inadequate. This potential remains largely untapped, as means of efficiently producing swine with appropriately expressed genetic modifications and the derivation of pluripotent stem cells meeting essential acceptance criteria of pluripotent human and murine lines are presently lacking. This laboratory is involved in collaborative efforts in the area of porcine pluripotent stem cell line derivation as a means of addressing both the need for better large animal genetic models as well as models of iPS-derived cell therapies