Hilda Jafarah
Engineering a Targeted Inhibitor to Prevent Ventricular Tachycardia
Abstract
Ventricular tachycardia (VT) is a dangerous irregular heart rhythm that can cause of sudden cardiac death. While defibrillation can end VT episodes, prevention of VT remains limited, especially after a heart attack (MI). We have identified a class of neutrophil-derived pore-forming-proteins (PFPs) as a likely driver of VT following MI. During the healing after an MI, immune cells called neutrophils accidentally release PFPs. While typically harmless to human cells, we found that PFPs can bind to stressed heart cells and kill them. Our research aims to engineer the first PFP inhibitor and evaluate its protective effects in a mouse model of spontaneous VT. Using yeast surface display, we will develop small, stable inhibitors that block PFP ability to bind and kill stressed heart cells. These inhibitors will be tested both in vitro and in vivo. This novel approach targeting the immune-VT axis could lead to breakthrough therapies for preventing life-threatening cardiac arrhythmias.
Receiving this fellowship is a transformative milestone in my scientific trajectory, enabling me to pursue novel high-risk research while developing the essential skills for establishing my independent laboratory and advancing therapeutic innovation.
