Effie Petersdorf

Our laboratory is engaged in understanding MHC gene function using hematopoietic cell transplantation from unrelated donors as a model system. The role of the HLA system has been established in solid organ and stem cell transplantation as pivotal for the acceptance of the engrafted tissue. Historically, alloantisera have been used to discriminate epitopes that define HLA antigens. With the advent of PCR-based tools in the mid-1980s, it became clear that a single serologically-defined antigen could be encoded by several unique sequences. Our effort has been directed at designing robust DNA-based methods to assay these single nucleotide polymorphisms (SNPs) in class I HLA-A, B, C and class II DRB1, DQB1 and DPB1 genes. Application of these methods has allowed a more precise and complete characterization of patients and unrelated donors. This work has elucidated the functional role of class II SNPs in acute graft-versus-host disease (GVHD), the role of class I SNPs in graft failure, and the importance of number of donor or recipient disparities in defining the overall success of unrelated donor transplantation. We have extended our studies to build an international effort among transplant centers, donor registries and laboratories to understand permissible mismatches. Hypotheses that we are currently testing include the identification of non-HLA SNPs having functional relevance in transplantation, and the application of molecular methods to understand the nature of SNPs having relevance in solid tumor model systems.