Project Grant R01DK144257

The National Institute of Diabetes and Digestive and Kidney Diseases, part of the Department of Health and Human Services National Institutes of Health, awarded $682,894 to St. Jude Children's Research Hospital Inc. on August 15, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to elucidate the role of LACTB2 in liver metabolic development.

The research identifies critical metabolic regulators and pathways required for liver maturation during postnatal development. The project focuses on determining how nutritional changes impact normal liver development and how LACTB2, a mitochondrial RNA endoribonuclease, regulates key metabolic processes to support liver maturation. Prior metabolomic profiling across six postnatal stages in mouse livers identified two critical transition phases: one associated with rapid liver growth and another with post-weaning dietary adaptation. Mice deficient in LACTB2 exhibited impaired liver development, metabolic dysfunction, and post-weaning mortality. Previous studies identified a loss-of-function LACTB2 mutation in an infant with severe liver dysfunction, with LACTB2 significantly upregulated during both critical transition phases. The project hypothesizes that LACTB2 controls mitochondrial RNA homeostasis to reinforce mitochondrial DNA-encoded oxidative phosphorylation protein expression during critical developmental periods.

Work is performed in Memphis, Tennessee. The period of performance runs through June 30, 2030. The assistance type is a Project Grant.