Guinea Pig Heart Failure Proteome at a Glance 2021

Signaling Networks in Heart Failure Progression

With Dr. Brian O’Rourke, we are looking at the impact of mitochondrially-derived reactive oxygen species (ROS) on kinase signaling in the failing heart. ROS impact both gene expression as well as the catalytic activity of many protein kinases and phosphatases. We have recently shown that curbing mitochondrial ROS with a mitochondrially-targeted antioxidant molecule called mitoTempo, both prevents the onset of heart failure and sudden cardiac death (HF/SCD) and rescues HF/SCD. MitoTempo not only blunts the impact of HF on the proteome but preserves the phosphorylation biosignature, by limiting maladaptive MAP kinase signaling and preserving PKA signaling.

Selected Publications

Foster DB, Liu T, Kammers K, O’Meally R, Yang N, Papanicolaou KN, Talbot CC, Jr., Cole RN, and O’Rourke B. Integrated omic analysis of a guinea pig model of heart failure and sudden cardiac death. J Proteome Res. 2016. 15(9): p. 3009-3028.

Dey S, DeMazumder D, Sidor A, Foster DB,* and O’Rourke B*. Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failure. Circ Res. 2018. 123(3): p. 356-371.