Project 466710

When Transplant Therapy Goes Awry: Investigating the Molecular Changes in Graft Versus Host DiseaseStem cell transplantation is a lifesaving treatment for people with advanced blood cancers. However, a serious complication of this therapy is chronic graft versus host disease, where immune cells from the donor attack the tissues of the recipient. Twenty-five percent of pediatric patients and 60% of adult patients develop chronic graft versus host disease, which is associated with permanent organ damage and a 10-25% mortality rate. Although the disease is common, the molecular changes that occur in patients organs are poorly understood. Previously, our research group developed a database of biological markers from blood samples of children with chronic graft versus host disease. Based on these markers, we are now generating diagnostic software to predict the risk of developing chronic graft versus host disease after transplant. In addition, this previous work found specific markers that may be related to disease severity, but how they cause ongoing damage is unknown. This project will investigate: (1) adult chronic graft versus host disease samples to validate our list of biological markers found in children and (2) the specific function of the markers linked to disease progression to identify potential drug targets for treatment. This project is important because chronic graft versus host disease frequently complicates a stem cell transplant, often with severe long-term consequences including death. Completion of my work will result in the development of a diagnostic tool to predict the occurrence of graft versus host disease, and the potential identification of new drug targets to improve treatment outcomes and quality of life for patients.