The Transplantation Immunology Program is dedicated to a greater understanding of the basic biology of transplantation of the lung allograft. This multidisciplinary program incorporates surgical, immunologic, and medical expertise in the care and research of patients with end-stage lung disease who undergo lung transplantation. The program faculty includes Dr. Maria Crespo, Dr. Steven Duncan, Dr. Bruce Johnson and Dr Timothy Corcoran.
Dr. Steven Duncan's work focuses on the role of the dendritic cell in immunologic tolerance of organ transplantation. Using a novel methodology of intravenous infusion of donor-derived thymic medullary dendritic cells, the immunologic tolerance of heterotopic airway allografts is being explored. The preliminary investigations have suggested a differential regulation of immune tolerance by dendritic cells of thymic and myeloid origin.
Other investigational work has focused on the use of an inhaled form of cyclosporine, a traditional anti-rejection drug, to control acute and chronic lung rejection. These investigators have hypothesized that higher concentrations of the drug will enter the transplanted lung by aerosol inhalation than could be achieved by the more traditional oral route, thereby facilitating better control of rejection while minimizing drug toxicity. Preliminary data have shown a favorable effect in regulating acute lung rejection and the investigators are currently completing a randomized NIH investigation. Late phase trials are underway using aerosol cyclosporine as rescue to treat patients with refractory acute rejection that failed to respond to all forms of conventional immunosuppression. A second major focus is to use the aerosol immunosuppressive medicine expertise present at UPMC to develop aerosol immunosuppressive systems for other more common lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis and asthma.
Dr. Timothy Corcoran's research is focused on the use of radionuclide testing to quantify the deposited dose of aerosol cyclosporine in the lungs of transplant recipients. Dr. Corcoran is also conducting in vitro studies to support the aerosol cyclosporine program and other aerosol medicine projects at UPMC. These studies include the research and development of respiratory adjuncts to increase the deposition levels of inhaled medications.
Dr. Corcoran is also conducting In vitro studies to support an upcoming trial at Children's Hospital of Pittsburgh that includes the use of Helium-Oxygen gas to increase the effectiveness of nebulizer bronchodilators, and a study examining aerosol deposition levels in throats of children using models reconstructed from MRI image sets. A partnership has been developed with Carnegie Mellon University for the use of phase Doppler particle characterization equipment allowing for the size characteristics of a given aerosol to be related to its in vivo behavior.
The Division also has a contract with the Department of Defense to explore new methodologies for aerosol drug delivery.