Basic Science Research

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The Department of Surgery’s research contributes to progress in the surgical field.

Investigative research into the mysteries of how the body functions leads to greater understanding of the interdependency of all medical disciplines.

Heart Valve Research

Historically, the main activities of the Heart Valve Laboratory have been the study the structure and function relationship of heart valve tissues.

Previous approaches to studying heart valve biomechanics have included:

  • Selective enzymatic digestion and biomechanical testing
  • Materials testing and constitutive modeling
  • Histologic and electron microscopy

New areas of investigation have built upon this basic understanding of valve function. The group has explored computational modeling as a tool for the study of soft tissue biomechanics, and tissue engineering as a means of fabricating the complex biological structures directly in the laboratory.

Also notable has been the work towards developing tissue-engineered heart valves, using the biological materials found in the natural tissues — elastin, collagen and glycosaminoglycans. These molecules can be synthesized by cells in culture or purified from tissues, then manipulated to mimic the normal structural framework of the aortic valve. This approach is particularly relevant to connective tissues that have limited ability for self-repair, like the cardiac valves.

Xenotransplantation

Organs derived from pigs (xenografts) represent a solution to the severe organ shortage that currently plagues human organ transplantation. The Xenotransplantation Laboratory, led by Mary Kearns-Jonker, PhD, is studying the immunology of xenograft rejection and the application of gene therapy to induce transplantation tolerance.

Ongoing research projects include:

  • Analysis of immunoglobulin genes used by organ recipients to target transplanted xenografts
  • Analysis of the molecular structure of xenoantibody-antigen binding, making use of site-directed mutagenesis and computer modeling
  • Development of treatment strategies to prevent graft rejection, including the application of anti-idiotypic antibodies and small molecular inhibitors designed to specifically target the xenoantibody binding site
  • The application of gene therapy to induce transplant tolerance

Mesenchymal Stem Cells in Autograft Fibrosis

Chronic rejection is a serious complication of organ transplantation, even in the presence of immunosuppression. Chronic rejection typically results in fibrosis of the graft — the laying down of excess extra cellular matrix until the organ becomes dysfunctional. Despite the widely appreciated magnitude of the problem and the numerous research efforts to control it, effective therapies to control allograft fibrosis are lacking. Fibroblasts are the sole cell type that forms the scar tissue that eventually leads to the dysfunction of the transplanted organs. The mechanisms that control the recruitment, differentiation and proliferation of intragraft fibroblasts are poorly understood. Recent data have suggested that proliferating intragraft fibroblasts are derived from transplant recipients. New findings indicate that mesenchymal stem cells (MSC) play an important role in the development of allograft fibrosis. The long-term goals of the research program are to apply genetic and cellular therapies for chronic rejection of solid organ transplants.