We completed a prospective metabolic screen in the pre-clinical model of cGVHD. This was accomplished through mass spectrometry studies. We, then, completed RNA sequencing of T cell subsets in the pre-clinical model, which confirmed metabolic perturbations observed in the prospective metabolic screening. Additionally, we performed single cell sequencing on CD4+ T cells extracted from target organs affected by cGVHD and from peripheral blood of patients who underwent HSCT and developed GVHD symptoms. Having identified several key metabolites perturbed in cGVHD, we used hyperpolarized 13C-pyruvate to image GVHD target organs in the pre-clinical model via MRI. Furthermore, we have begun testing metabolic inhibitors for pathways utilized by pathogenic T cells in pre-clinical GVHD models. Metabolic imaging of patients undergoing hematopoietic stem cell transplantation is planned. Testing of metabolic drugs to treat patients with cGVHD is planned.
