Federal Project Grant Award Summary

Mayo Clinic received a $634,994 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective April 1, 2026, with completion targeted for January 31, 2030. The award supports fundamental biomedical research investigating the molecular mechanisms underlying sexually dimorphic traits of interstitial cells of Cajal (ICC) and their role in gastrointestinal neuromuscular disorders. The research addresses the significantly higher prevalence of gastroparesis and other gastrointestinal motor disorders in women compared to men by examining how estrogen signaling and gene regulatory circuitry differentially affect ICC function, mitochondrial integrity, and disease susceptibility in females versus males.

The project delivers basic science research outputs focused on elucidating disease mechanisms and identifying potential therapeutic targets for gastrointestinal motor disorders with female predominance. Specific deliverables include experimental findings on female-biased gene regulatory pathways controlled by estrogen receptor GPER1 and polycomb complex NCPRC1.5, comparative analyses of sex-specific mitochondrial stress responses in ICC, and mechanistic insights into histone serotonylation's protective effects in male cells. These research outcomes are intended to advance understanding of why women experience four times higher rates of diabetic gastroparesis and establish a potential mechanistic link between metabolic and immune etiologies of gastrointestinal dysfunction, ultimately contributing to the development of sex-informed prevention and treatment strategies.