Federal Grant Award Summary

The National Cancer Institute (NCI) awarded The Ohio State University $463,692 under the Cancer Biology Research program (CFDA 93.396) to conduct fundamental research on the structural and dynamic characterization of human K-RAS protein and its interactions with binding partners and small-molecule ligands. The project, which commenced June 1, 2026, and concludes May 31, 2031, employs state-of-the-art experimental and computational methods to investigate K-RAS in both normal and dysregulated states. Given that K-RAS mutations are directly associated with approximately 25% of all human cancers, this research aims to provide comprehensive insights into how oncogenic K-RAS mutants (including G12C, G12D, and G12V variants) perpetually activate cancer-signaling pathways, potentially informing the development of improved prevention, detection, and treatment strategies for neoplastic diseases.

The project leverages recent breakthroughs from the principal investigator's laboratory that have overcome critical obstacles in understanding K-RAS functionality, including the full characterization of functionally critical switch regions by nuclear magnetic resonance (NMR) spectroscopy and the ability to work with native guanosine triphosphate (GTP) rather than synthetic analogs. The deliverables include comprehensive structural-dynamics ensemble characterization of wild-type and mutant K-RAS variants in the presence and absence of protein binding partners and small-molecule drug candidates, such as MRTX1133, using NMR spectroscopy and computational modeling approaches. Research will be conducted at the Columbus, Ohio facility of The Ohio State University's Office of Sponsored Programs.