Federal Grant Award Summary

Cincinnati Children's Hospital Medical Center received a $445,500 Project Grant from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865), awarded June 1, 2026, with completion targeted for May 31, 2028. This research initiative aims to define how dominant-negative RBPJ disease alleles impact Notch signaling outcomes and contribute to Adams-Oliver Syndrome (AOS), a rare developmental disorder characterized by scalp aplasia cutis congenita and multiple organ system defects. The research employs novel conditional mouse models to investigate the molecular mechanisms by which AOS-associated RBPJ variants alter Notch signal strength and cellular decision-making, with particular focus on understanding why these variants produce AOS phenotypes rather than Alagille syndrome-like presentations.

The grant supports two primary research aims designed to dissect the tissue-specific pathogenesis underlying AOS through mechanistic and cellular studies. The project leverages animal models that demonstrate AOS-like phenotypes and differential lethality associated with Notch1 versus Notch2 haploinsufficiency to elucidate the molecular defects driving disease manifestation. By combining conditional genetic approaches with comprehensive phenotypic analysis, the research is expected to advance fundamental understanding of Notch pathway biology relevant to developmental disorders and generate insights applicable to human patient care and potential therapeutic interventions.