New Investigator Research Grant Program

Every year in the US, more than 6,000 patients receive hematopoietic cell transplantation (HCT) to cure refractory and relapsed hematologic malignancies via Graft-versus-Leukemia (GVL) effect. Donor immune cells, called T lymphocytes are critical for GVL, but often attack and damage normal peripheral patient’s tissues after HCT, causing acute Graft-versus-Host Disease (aGVHD), which significantly contributes to post-transplant morbidity and mortality and which is challenging to separate from GVL. Importantly, current therapies for aGVHD control increase the risk of leukemia relapse and of life-threatening infections, which underscores a critical unmet need for development of more effective and safe anti-aGVHD therapy.

Our group recently discovered a major contribution of specific subset of T lymphocytes, called tissue-resident T (Trm) cells, to the peripheral target organs during aGVHD. Notably, differentiation of Trm cells from immigrated precursors is associated with up-regulation of gene RGS1, which is important for Trm retention in tissues and which may represent a novel molecular target for therapeutic intervention. Here, we seek to answer 3 critical questions: 1) What factors cause RGS1 up-regulation during aGVHD? 2) How does RGS1 deletion protect from aGVHD? and 3) Does RGS1 loss preserve GVL effect?

By advancing our knowledge about aGVHD and GVL, this project is expected improve the survival and quality of life for HCT patients with high-risk leukemias and lymphomas.