Project description:Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD (GSE73723). Within these profiles we discovered potentially druggable targets not previously implicated in GVHD, prominently including aurora kinase A (AURKA). In this study, we performed a planned comparison of AURKA gene expression in HCT-recipients with clinical GVHD and compared it to expression in HCT-recipients without clinical GVHD.
Project description:Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. This transcriptome analysis enables an unsupervised approach to the identification of targets for disease control using a model with an immune system that closely overlaps with the human and has a high degree of cross-reactivity with human antibody-based therapeutics.
Project description:Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with KY1005 monotherapy and KY1005/Sirolimus combination therapy
Project description:Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with FR104 monotherapy and FR104/Sirolimus combination therapy
Project description:Tissue-specific T cell immune responses play a critical role in maintaining organ health, but can also drive immune pathology during both auto- and alloimmunity. The mechanisms controlling intra-tissue T cell programming remain unclear. Here, we leverage a non-human primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HCT) to probe the biological underpinnings of tissue-specific alloimmune disease, using a comprehensive systems immunology approach.Transcriptional profiling revealed substantial biological differences between T cells, infiltrating the lung and liver during aGVHD.