Dr. Shuibing Chen and Dr. Todd Evans (co-PIs) have been awarded a grant for over $4M from the National Heart Lung and Blood Institute for a new R01 entitled “Dissecting the molecular pathways controlling human pacemaker development. The human sinoatrial node (SAN) is the heart’s natural pacemaker, initiating electrical impulses that maintain rhythmic contraction and coordinate blood flow. While its role is essential, our understanding of SAN development—particularly in humans—remains limited. Sinus node dysfunction (SND), often caused by SAN cell loss or fibrosis, is a major cause of arrhythmia and the primary reason for up to 50% of artificial pacemaker implants in the US. There are no approved cellular or pharmacological treatments for SND, beyond relieving symptoms or pacemaker implantation. The NIH project proposed by Drs. Chen and Evans aims to uncover how the human SAN develops and functions, by identifying the key genes and signals that guide its formation and cellular composition. Using advanced stem cell models, gene editing tools, and organoids (cardioids) with functional pacemaker activity, they will also study how genetic risk variants linked to heart rhythm disorders affect SAN development and function. These insights could lead to new strategies for treating sinus node dysfunction and other heart conduction diseases.