Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded The Children's Hospital of Philadelphia Research Institute a $889,804 Project Grant on July 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837). The award funds basic and translational research investigating MED12 (Mediator Complex Subunit 12) as a novel regulator of vasculogenesis, with completion targeted for March 31, 2031. The research leverages a MED12-deficient zebrafish model with fluorescent endothelial cell visualization capabilities to elucidate the molecular mechanisms underlying Hardikar syndrome, a rare vascular malformation disorder affecting cerebral, pulmonary, and abdominal vessels. Deliverables include experimental findings on MED12's role in regulating YAP and TGFβ signaling pathways critical to vascular development and remodeling, isolation and characterization of vascular endothelial cells via fluorescence-activated cell sorting, and mechanistic insights into transcriptional and non-transcriptional functions of MED12 in vasculogenesis.

The project directly addresses a significant clinical gap: therapeutic options for vascular malformations remain limited due to incomplete understanding of their pathogenesis, and complications include stroke, internal bleeding, disfigurement, and sudden death from vascular rupture. By identifying MED12 as a previously unexplored player in vascular biology, this research nominates novel transcription-based therapeutic targets and provides foundational biological insights applicable to both rare disease treatment and broader cardiovascular research.