Date: Mar. 9th 2023
Wende was awarded an R01 from NHLBI of the NIH entitled, “Novel roles of PDK2 in heart failure: Regulation of mitochondrial nuclear crosstalk via metabolic regulation and histone acetylation” (1R01HL167872-01). A brief introduction to the project: Cardiovascular disease is the number one cause of mortality in the United States, with different etiologies of heart failure associated with distinct changes in mitochondrial substrate selection, utilization, and gene expression mediating these differences. Here we test the hypothesis that one family of kinases that regulate this process (i.e., PDKs) play distinct roles in mortality, cardiac hypertrophy, mitochondrial oxidative metabolism, and signaling to transcriptional pathways in the nucleus mediated by epigenetics (i.e., histone acetylation). We have developed new animal model systems of inducible and cardiomyocyte specific loss-of-function mice of the two cardiac enriched isoforms of this pathway (i.e., PDK2 and PDK4) to determine the mechanism of this regulation and test the potential of their isoform-specific impact on pressure-overload induced heart failure.
