Federal Grant Award Summary

Weill Medical College of Cornell University received a $1,657,587 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded on July 15, 2026, with completion anticipated by March 31, 2028. The grant supports fundamental research to dissect the molecular pathways controlling human sinoatrial node (SAN) development, the heart's natural pacemaker. The research addresses a critical clinical gap, as sinus node dysfunction—caused by SAN cell loss or fibrosis—is the primary indication for approximately 50% of artificial pacemaker implants in the United States, yet no approved cellular or pharmacological treatments currently exist.

The project delivers three integrated research products: (1) identification of key transcriptional regulators of SAN differentiation through CRISPR interference and activation approaches in human pluripotent stem cells (hPSCs), with validation in functional SAN organoid and SAN-paced cardioid models; (2) dissection of molecular programs guiding SAN subpopulation specification across head, tail, and transitional zone domains using CRISPR-based perturbation and single-cell RNA sequencing; and (3) assessment of how genetic variants associated with sinus node dysfunction affect SAN development. The research leverages innovative tools including a dual knock-in hPSC reporter line (SHOX2:EGFP; MYH6:mCherry) and established protocols for generating functional pacemaker tissue models, enabling real-time visualization, isolation, and electrophysiological analysis of human pacemaker cells.