Grant Award Summary

The University of Chicago received a $547,740 Project Grant from the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research program (CFDA 93.393), effective July 1, 2026 through June 30, 2031. This award funds research defining the molecular mechanisms underlying RNA binding by the MLL1 (KMT2A) histone modification complex in acute myeloid leukemia (AML) etiology. The research challenges the current model that specific long noncoding RNAs (lncRNAs) like HOTTIP recruit the MLL1 complex through selective binding to the WDR5 subunit. Instead, the project tests two alternative hypotheses: (1) that non-specific RNA binding inhibits the MLL1 complex's histone methyltransferase activity as a novel regulatory mechanism in leukemia, and (2) that the RBBP5 subunit—rather than WDR5—accounts for specific HOTTIP recruitment through a mapped 24-nucleotide motif.

The research deliverables encompass detailed mechanistic studies of RNA-protein interfaces within the MLL1 core complex, with findings intended to advance understanding of leukemogenesis and potentially inform cancer prevention and treatment strategies. This five-year project represents fundamental discovery research consistent with the NCI program's focus on identifying cancer causes and developing prevention mechanisms in humans.