Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for high-risk malignant and nonmalignant hematologic disorders. Donor allo-T cells drive the curative graft-versus-tumor (GVT) effect; however, allo-Tcells also cause acute graft-versus-host disease (aGVHD), which remains a major complication of allo-HSCT. Long noncoding RNAs (lncRNAs) control gene expression with tissue specificity and fine-tune immune responses, but their role in alloimmune T cell responses is largely undefined. Using well-annotated clinical HSCT samples, lncRNA regulators of allogeneic T cells were identified. However, the molecular mechanisms and in vivo functions of these lncRNAs are unknown. The Peltier Lab uses murine allogeneic and xenogeneic models of aGVHD to determine the in vivo functions of these lncRNAs. Molecular mechanisms are explored both in vivo and in vitro using a variety of techniques.
LncRNA molecular mechanisms are diverse and include coding for previously unrecognized functional microproteins. The role of lncRNA-encoded microproteins in T cell-intrinsic function has not been described. The Peltier Lab uses allogeneic and xenogeneic murine models of aGVHD, to determine the in vivo function of recently discovered microproteins encoded by lncRNA genes. The molecular mechanisms of these microproteins are determined using cutting-edge techniques including RNA sequencing and assessment of chromatin accessibility at the single cell level.
Overall, the Peltier Lab seeks to unlock the role of lncRNAs and unrecognized microproteins encoded by lncRNAs in alloimmunity. The tissue- and context-specificity of lncRNAs may make them ideal candidates for new diagnostic tests or targets of new medicines that may lead to improved outcomes following allogeneic HSCT. By exploring the uncharted role of lncRNAs and microproteins in T cell biology, these studies may also reveal new insights for other T cell-mediated disorders.
The Peltier Lab is located within the Hematologic Malignancies and Stem Cell Biology research group at the Herman B Wells Center for Pediatric Research.