The central hypothesis guiding our Network is that by understanding calmodulin kinase II (CaMKII) regulation, defining the role of ‘upstream’ CaMKII effectors and ‘downstream’ CaMKII molecular targets, we will significantly contribute to development of the next generation of highly specific therapies for heart failure and arrhythmias.
The purpose of our network is to coordinate the scientific efforts of international leaders and collaborators, each with unique expertise, to focus on the common theme of CaMKII biology in heart in an integrative manner, whereby the ‘whole’ can be greater than the sum of individual contributions.
The long term goal of our network is to advance the development of new therapies based on CaMKII and downstream CaMKII targets. Secondary goals are to strengthen existing collaborations and create new training opportunities between Network sites that will enable further EU-North American partnerships for the next generation of physicians and scientists.Specific Aims
Specific Aim 2
Determine the CaMKII-dependent mechanisms for myocardial dysfunction and heart failure.
Specific Aim 3
A) Identify new CaMKII binding partners in normal and diseased human and animal heart tissue.
B) Identify mutations and polymorphisms in CaMKII, upstream CaMKII effectors and downstream CaMKII targets.
Specific Aim 4
Quantify the role of CaMKII signaling to downstream targets in arrhythmias, by improving mathematical models of CaMKII signaling in heart and utilizing new data from cellular and animal models.