Project Grant R03DK149205

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Wayne State University $116,250 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847).

The award funds research into the role of MAFA and MAFB transcription factors in maintaining human pancreatic beta cell maturity and function through histone methylation. The research tests the hypothesis that these transcription factors regulate gene expression via interactions with histone modifiers to induce and maintain beta cell maturity in humans, and that loss of this function during type 2 diabetes promotes beta cell dedifferentiation to a more immature state. Preliminary data from bulk RNA-sequencing of beta cell-enriched pseudoislets with MAFA and MAFB knockdown identified differential gene expression patterns consistent with PRC2-complex mediated histone H3K27ME3 silencing. The research will examine histone methylation marks (H3K27ME3, H3K4ME1, and H3K27AC) at enhancers and the interaction of MAFA and MAFB with MLL3/4 histone modifiers to elucidate mechanisms of beta cell maturation.

Work is performed in Detroit, Michigan. The period of performance runs from September 1, 2026, through August 31, 2028. This is a Project Grant assistance type supporting basic biomedical research that improves understanding of disease mechanisms and leads to improved prevention, diagnosis, and treatment across NIDDK programmatic areas.