Epigenetic regulation of adaptive and maladaptive effects of O-GlcNAc modifications in the diabetic heart (B03)

• Subject Area: Endocrinology, Diabetology, Metabolism ; Cardiology, Angiology
• Term: from 2014 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236360313

It is the focus B03 to analyze the pharmacological manipulation of the crosstalk between CaMKII-mediated phosphorylation of Ser-632 and O-GlcNAcylation of Ser-642 of histone deacetylase 4 (HDAC4). We developed a lead compound that specifically reduces CaMKII-mediated prevention of cardioprotective O-GlcNAcylation. This compound will be tested in diabetes animal models to explore whether late complications including cardiomyopathy but also nephropathy can be attenuated. In addition, we will investigate whether the underlying biochemical processes that we identified in the heart also take place in blood cells of in vivo model systems as well as patients, and whether these can be used as biomarkers for late diabetic complications.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1118: Reactive metabolites as a cause of diabetes complications
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Johannes Backs; Professor Dr. Oliver J. Müller, until 6/2018