Our research centralizes on the redox environment of the heart – how it varies with disease, whether these variations protect or injure the myocardium, and to what extent we can leverage the protective mechanisms we uncover to design novel therapeutics. Utilizing several cutting-edge techniques in high-resolution cellular imaging and biochemistry we study these fundamental questions related to patho-biology, while integrating our findings with studies in animal models and human cells to investigate disease causation.
Recently, our research has been focused on the emerging concept that certain kinases (bioactive signaling mediators in the cell) can be redox sensitive, with their activity and regulatory function rapidly altered by local oxidant production. We’ve discovered that signaling via one of the heart’s master kinases, PKA, is particularly sensitive to the cellular redox state, with stress-induced oxidation of PKA leading to cardioprotective signaling events that aid cell survival immediately following a heart attack. However, new data looking in chronic disease shows that activation of this signaling cascade diminishes over time, contributing to sustained cardiac cell death, structural remodeling, and heart failure. The W.W. Smith Trust funded work we are just beginning aims to tackle why this signaling cascade breaks down over time, how it drives persistent cell death, and whether we can therapeutically re-activate oxidized PKA signaling to improve long-term heart function. Our hope is that a more developed understanding of these very important processes will foster new treatments for heart failure, and ultimately reduce the number of people dying each year from this debilitating disease.
Jillian Simon, PhD’s research centralizes on the redox environment of the heart – how it varies with disease, whether these variations protect or injure the myocardium, and to what extent we can leverage the protective mechanisms we uncover to design novel therapeutics. W. W. Smith Charitable Trust Research Project: “Spatiotemporal regulation of PKA signaling in ischemic heart disease”