Federal Project Grant Award Summary

Northeastern University received a $224,400 Project Grant from the National Cancer Institute (NCI) under the Cancer Biology Research program (CFDA 93.396), awarded August 1, 2026, with completion targeted for July 31, 2029. The award funds development of a direct RNA sequencing platform to detect and map uridine modifications—specifically dihydrouridine (D)—in human lung cancer transcripts at single-nucleotide resolution. The research addresses a critical gap in cancer biology by creating the first broadly applicable technology to distinguish dihydrouridine from pseudouridine and standard uridine modifications transcriptome-wide, leveraging Nanopore direct RNA sequencing and machine learning classification frameworks.

Under the exploratory phase (R61), the research team will establish knockout and overexpression cell lines for DUS1L and DUS2 enzymes, develop machine learning classifiers targeting 80% three-way accuracy in distinguishing the three uridine variants using synthetic RNA controls, and validate the platform against lung adenocarcinoma tumors and matched normal tissues from the NCI Cooperative Human Tissue Network. The anticipated deliverables include a high-confidence atlas of dihydrouridine sites in cancer cells, optimized machine learning algorithms integrated into the ModQuant pipeline, and transcriptome-wide mapping data that will advance understanding of RNA modification roles in cancer biology and inform potential therapeutic applications.