Federal Grant Award Summary

The University of North Carolina at Chapel Hill received a $693,182 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 10, 2026, with completion targeted for March 31, 2030. This award funds research investigating the role of the DDX3X (DEAD-box helicase 3 X-linked) gene in regulating sex-specific differences in cardiac development and congenital heart disease (CHD). The research deliverables include mechanistic studies using conditional genetic models in mice to elucidate how DDX3X regulates sex-dependent cardiac excitation-contraction coupling and the identification of DDX3X target messenger RNAs (mRNAs) critical to female cardiac function, with particular focus on post-transcriptional regulation through mRNA translation.

The project addresses a significant scientific gap by examining why certain congenital heart diseases exhibit sex bias, with prior clinical evidence linking DDX3X mutations to CHD in females but not males. The research team will employ molecular and cellular biology techniques to define the cardiac DDX3X protein interactome and characterize its interactions with translation machinery and genes essential to cardiac function. Results from this hypothesis-driven basic research are expected to advance understanding of sex-specific mechanisms in cardiac development and potentially inform therapeutic strategies for preventing or treating sex-differentiated forms of congenital heart disease.