Project Grant R01HD120311

The National Institute of Child Health and Human Development awarded The General Hospital Corporation (Massachusetts General Hospital) $538,173 on August 1, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865, assistance type: Project Grant) to investigate the molecular mechanisms controlling developmental timing through NADH redox metabolism.

The project uses a segmentation clock—a molecular oscillator whose period correlates with embryonic development duration—to identify how species-specific developmental rates are set. Using mouse and human pluripotent stem cells, the research examines the cytosolic NAD+/NADH ratio as a key regulator of developmental speed. Preliminary findings indicate that the ratio is elevated in mouse cells (fast-developing) compared to human cells (slow-developing), and experimentally modulating this ratio accelerates or decelerates the segmentation clock. The award funds investigation of differential cytosolic NAD+/NADH ratios between species, with focus on NADH shuttling systems—specifically the glycerol-3-phosphate (G3P) and malate-aspartate (MA) shuttles—that regulate redox balance by transferring reducing equivalents from cytosol to mitochondria. Preliminary data suggest the G3P shuttle is more active in mouse embryonic cells than human cells due to differential enzyme expression. Understanding species-specific developmental rates holds translational potential for accelerating stem cell differentiation in cell therapies and decelerating cellular processes to combat tumor growth and aging.

Work is performed in Boston, Massachusetts. The period of performance runs through April 30, 2031.