Project Grant K99HL179374

Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded a Project Grant of $153,494 to Stanford University (The Leland Stanford Junior University) on July 10, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837). The award funds a five-year research initiative investigating the mechanisms of tyrosine kinase inhibitor (TKI)-induced sinoatrial node dysfunction (SAND) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients. The research deliverables include the development and characterization of human induced pluripotent stem cell-derived sinoatrial node-like cells (iSANCs) to model clinical SAND phenotypes, single-cell transcriptomic analysis to identify dysregulation pathways, electrical remodeling assessments of calcium and membrane clock mechanisms, and evaluation of therapeutic rescue approaches using engineered heart tissues and mouse models.

The project addresses a critical safety gap in cancer treatment by elucidating how ALK inhibitors disrupt cardiac automaticity through off-target kinase effects and proposes targeted protein kinase interventions to reverse SAND phenotypes. Deliverables will include peer-reviewed publications, novel in vitro and in vivo models for ALKI-induced cardiotoxicity, transcriptomic datasets, and preclinical evidence supporting potential therapeutic countermeasures to enhance patient safety in ALK-positive NSCLC treatment. The work concludes May 31, 2028, and is performed at Stanford's Palo Alto, California campus.