Project Grant R21AI194203

The National Institute of Allergy and Infectious Diseases awarded ST Jude Children's Research Hospital Inc. $277,500 on August 12, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to engineer a synthetic IL-33 receptor that enhances T-cell function for treating autoimmune disorders and cancer.

The research systematically examines regulatory nodes governing T-cell differentiation and function, including environmental cues, signaling pathways, metabolism, transcription factors, and epigenetic regulators. The project targets the IL-33-ST2 signaling axis, which previous studies show promotes regulatory T-cell suppression of autoimmune inflammation and tissue damage while helping cytotoxic CD8 T cells kill tumor cells. The research team proposes engineering a synthetic IL-33 receptor ST2 that, when expressed in T cells, will transduce strong and durable signaling to overcome the inherent limitations of regulatory T cells and CD8 T cells constrained by environmental factors and cell-intrinsic programs. This synthetic approach will enhance signaling strength and duration beyond cells' inherent capacity, potentially overriding the downregulation of T-cell receptor and co-stimulatory signaling observed in dysfunctional T cells.

The award period extends from August 12, 2026, through July 31, 2028. Work is performed in Memphis, Tennessee.