) One major barrier limiting the success of human allotransplantation is the transplantation related infec- tious complications. While significant progress has been made in the last decade in elucidating the pathogenesis and the optimal management of trans- plant infectious complications, a number of infections continue to cause sig- nificant morbidity and mortality in the transplant recipient. The applicant is an active clinical investigator in this field and has identified two major areas in which additional research is required to overcome the impact of these infections. These include addressing the role of the family of beta-herpes viruses (CMV, HHV-6, and HHV-7) and Epstein Barr Virus (EBV) induced post- transplant lymphoproliferative disease (PTLD). This clinical research is a fertile ground for training of future clinician investigators as it conveys multidisciplinary interaction: immunology, diagnostic virology, and transplan- tation medicine. Through this award, the applicant is seeking the support to obtain additional training in specific aspects of clinical research including formal courses in patient-oriented research, interactions with the clinical research unit (GCRC), GMP facilities, and additional training in immunotherapy of chronic viral infections in transplant patients. The applicant is seeking the support to, within a clinical research group, address the two mentioned focused areas in infectious diseases in transplantation and in which future clinician investigators will be formally trained.
The specific aims that this application will pursue include: I) Study the clinical relevance of HHV-6 and HHV-7 in organ transplant recipients and their interaction with other opportu- nistic viral infections (CMV, EBV, HBV, and HCV). II) Define the clinical value of EBV viral load for the prevention and management of EBV-PTLD, and test the feasibility of cell-based immune therapy for the prevention and trea- tment of EBVPTLD in EBV naive solid organ transplant recipients. Altogether, this award will allow us to address, through rigorous patient-oriented re- search, two areas of transplant infectious complications, which are limiting success in human transplantation. Moreover, it will facilitate to train a cadre of future clinician investigators who will further advance this impor- tant field of clinical medicine.
