Project Grant R01CA305980

The University of North Carolina at Chapel Hill received a $653,846 Project Grant award from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) for the period July 1, 2026 through June 30, 2031. The award supports the development of novel cancer therapeutics through targeted protein degradation (TPD), an emerging therapeutic strategy that recruits proteins of interest to cellular degradation machinery for destruction. The research focuses on hijacking the FBXO22 F-box protein to develop a previously unutilized E3 ubiquitin ligase recruitment strategy that expands the available chemical toolkit beyond the limited options currently available (primarily VHL and cereblon-based approaches).

The primary deliverables include the discovery, development, and evaluation of degradation-based therapeutic compounds targeting NSD2 (nuclear receptor-binding set domain-containing 2) for multiple cancer types, including multiple myeloma and acute lymphoblastic leukemia. This research addresses a critical gap in cancer treatment development by leveraging FBXO22's increased expression in many cancer types to enable more selective and tissue-specific protein degradation approaches. The project supports fundamental and applied laboratory research aimed at advancing TPD as a viable therapeutic modality and potentially expanding the druggable proteome for cancer treatment applications.