Project Grant R01DK149654

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Ohio State University $807,563 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) for Project Grant R01DK149654.

The award funds development of potent, selective Type III CD38 inhibitors as first-in-class therapeutics to reduce ischemia-reperfusion injury in liver transplantation. Current CD38 inhibitors lack topology selectivity, requiring doses over 100-fold higher than necessary to achieve hepatoprotection; this award supports creation of inhibitors with IC50 below 100 nanomolar to enable superior donor organ protection and improved transplantation outcomes. The research identifies intracellular Type III CD38, not the well-characterized Type II membrane form, as the key driver of hepatic ischemia-reperfusion injury, with hepatocyte NAD+ depletion as the primary injury mechanism.

The work includes cell-type-specific mechanistic studies using Cre-inducible CD38 knockout mice with hepatocyte, liver sinusoidal endothelial cell, and myeloid-lineage-specific drivers to determine which cell types drive injury and when CD38 activity becomes critical. Inhibitors will be tested at multiple timepoints from 30 minutes before through 6 hours after reperfusion.

Performance takes place in Columbus, Ohio. The period of performance runs through June 30, 2030.