Over the last 15 years, significant improvements in patient outcome have occurred such that heart transplantation is now considered an established therapy with a high likelihood for short-term success. However, the emotional, financial, social and medical burdens placed on patients and families remain enormous and heart transplantation therapy remains palliative. Indeed, most children transplanted in infancy and childhood are not predicted to survive to adulthood. The immunosuppressive regimens have many inherent risks including infections, malignancy and multiple end-organ toxicities. Furthermore, these agents have had little impact on the development of chronic rejection, the leading cause of death late after transplantation. The central paradigm driving this integrated SCCOR proposal is that further improvements in clinical outcome following pediatric heart transplantation depend upon novel strategies that link basic science advances with evidence-driven modifications in clinical protocols. This SCCOR proposal will bring together experts in the fields of pediatric cardiology (cardiac transplantation) and cardiac surgery, immunology, infectious disease, molecular genetics, and biostatistics to advance the common goal of developing novel approaches to the management of pediatric heart transplant recipients. Our long-term goals are to: 1. Develop strategies that result in long-term graft acceptance without requiring immunosuppression. 2. Develop strategies to reduce the morbidities related to non-specific immunosuppressive protocols. 3. Identify genetic markers that predict disparities in transplant outcomes in children after transplantation, including racial disparities. 4. Develop non-invasive diagnostic strategies for rejection surveillance that reduce cost and improve quality and length of life. This Pediatric CV SCCOR proposal addresses each of these areas with novel, hypothesis driven projects to rapidly and significantly advance the state-of-the-art care for pediatric heart transplant recipients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-S (S1))
Program Officer
Massicot-Fisher, Judith
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Medicine
United States
Zip Code
Van Driest, Sara L; Webber, Steven A (2015) Pharmacogenomics: personalizing pediatric heart transplantation. Circulation 131:503-12
Feingold, Brian; Brooks, Maria M; Zeevi, Adriana et al. (2012) Renal function and genetic polymorphisms in pediatric heart transplant recipients. J Heart Lung Transplant 31:1003-8
Wiesmayr, Silke; Webber, Steven A; Macedo, Camila et al. (2012) Decreased NKp46 and NKG2D and elevated PD-1 are associated with altered NK-cell function in pediatric transplant patients with PTLD. Eur J Immunol 42:541-50
Macedo, Camila; Webber, Steven A; Donnenberg, Albert D et al. (2011) EBV-specific CD8+ T cells from asymptomatic pediatric thoracic transplant patients carrying chronic high EBV loads display contrasting features: activated phenotype and exhausted function. J Immunol 186:5854-62
Feingold, Brian; Arora, Gaurav; Webber, Steven A et al. (2010) Cost-effectiveness of implantable cardioverter-defibrillators in children with dilated cardiomyopathy. J Card Fail 16:734-41
Ohmann, Erin L; Burckart, Gilbert J; Brooks, Maria M et al. (2010) Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients. J Heart Lung Transplant 29:509-16
Davies, Michael L; Xu, Shushen; Lyons-Weiler, James et al. (2010) Cellular factors associated with latency and spontaneous Epstein-Barr virus reactivation in B-lymphoblastoid cell lines. Virology 400:53-67
Ohmann, Erin L; Brooks, Maria M; Webber, Steven A et al. (2010) Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients. J Heart Lung Transplant 29:1342-51
Lau, Audrey H; Soltys, Kyle; Sindhi, Rakesh K et al. (2010) Chronic high Epstein-Barr viral load carriage in pediatric small bowel transplant recipients. Pediatr Transplant 14:549-53
Ohmann, Erin L; Burckart, Gilbert J; Chen, Yan et al. (2010) Inosine 5'-monophosphate dehydrogenase 1 haplotypes and association with mycophenolate mofetil gastrointestinal intolerance in pediatric heart transplant patients. Pediatr Transplant 14:891-5

Showing the most recent 10 out of 30 publications