Project Grant R01DK146380

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Johns Hopkins University $2,503,175 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate toll-like receptor 4 (TLR4)-mediated pancreatic islet dysfunction in necrotizing enterocolitis (NEC) pathogenesis and develop novel treatments.

The research examines how TLR4-induced pancreatic islet loss leading to hyperglycemia plays a causative role in NEC development across mice, piglets, and human infants. The investigation will characterize upstream regulators of TLR4 signaling and barrier injury, establish the mechanistic link between hyperglycemia and intestinal barrier dysfunction, and test therapeutic strategies to enhance pancreatic regeneration and prevent NEC progression. Prior findings show that islet reduction precedes NEC onset in human infants, that insulin reversal of hyperglycemia prevented NEC in mice, and that enhancing islet regeneration via adenoviral gene transfer or PPAR activation reduced NEC severity. The study will validate TLR4 inhibition and islet regeneration as potential intervention targets.

Performance occurs in Baltimore, Maryland, with a period of performance from September 1, 2026, through August 31, 2030. The award is structured as a Project Grant, the standard assistance type for NIH research funding.