Federal Project Grant Award Summary

St. Jude Children's Research Hospital Inc. received a $628,073 Project Grant award from the National Cancer Institute (NCI) under the Cancer Biology Research program (CFDA 93.396), effective June 1, 2026 through May 31, 2031. The award funds research to mechanistically dissect and target non-cell autonomous tumor promotion mechanisms in DICER1 cancer predisposition. The project employs a fusion-negative rhabdomyosarcoma (FN RMS) mouse model to investigate how germline heterozygous loss-of-function mutations in DICER1—a ribonuclease III enzyme critical for microRNA (miRNA) processing—contribute to pediatric tumorigenesis. The research examines how secondary somatic mutations in the RNase IIIB domain impair 5p miRNA processing and create global miRNA imbalance, with specific focus on tumor-stromal interactions and microenvironmental mechanisms that cannot be adequately modeled in vitro.

The deliverables from this NCI-funded research initiative are expected to elucidate fundamental mechanisms of cancer predisposition in DICER1-associated malignancies, including rare pediatric tumors such as pleuropulmonary blastoma. By identifying non-cell autonomous mechanisms of tumor promotion within an intact immune system context, the project aims to inform development of targeted therapeuties for pediatric patients with DICER1-associated tumors and potentially benefit broader cancer populations with altered miRNA processing. The five-year project is conducted at St. Jude's Memphis, Tennessee facility and aligns with the Cancer Biology Research program's objective to provide fundamental information on cancer mechanisms to advance prevention, detection, diagnosis, and treatment methodologies.