Federal Project Grant Award Summary

Yale University received a $1.68M Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 1, 2026, with completion targeted for April 30, 2028. The award funds basic science research investigating the developmental cellular and molecular mechanisms underlying Circle of Willis (CW) formation and maintenance—a critical collateral circulatory system in the brain that provides redundant oxygenated blood supply and protects against cerebrovascular disease. The research leverages zebrafish models and human induced pluripotent stem cell (iPSC)-derived vascular organoids to elucidate how microRNA-125A (mir-125a) regulates embryonic brain angiogenesis and how mitochondrial metabolism influences CW artery formation and stability.

The project addresses fundamental gaps in understanding developmental origins of anatomical variations in the Circle of Willis, which are surprisingly common in human populations yet remain largely unexplained at the molecular level. By identifying how mir-125a loss-of-function leads to incomplete CW formation through altered mitochondrial biogenesis and oxidative metabolism, the research aims to establish whether these vascular variations are established during embryonic development and whether they could be corrected to protect against vascular stress. Deliverables include mechanistic discoveries regarding the genotype-phenotype relationship in CW development, experimental validation across multiple model systems, and foundational knowledge to support future therapeutic interventions for cerebrovascular disease prevention.