Our laboratory’s primary goal is to understand the mechanisms that link perturbations in metabolism to the development of heart disease.
Specifically, work in the laboratory has two mechanistic goals: 1) to determine the role of metabolic substrate switching in the hearts of individuals with diabetes or heart failure, and 2) to define the role of cellular glucose delivery on both post-translational regulation of mitochondrial enzymes and their activity as well as metabolic signaling to epigenetic regulation of gene expression that together may lead to the development of diabetic cardiomyopathy.
Finally, emerging work from our group examining human heart samples has identified heart failure etiology specific and racial differences in epigenetic changes that in turn impact susceptibility to heart failure.
By determining these molecular signatures of altered protein regulation and DNA structure/regulation we aim to provide critical knowledge to determining future therapeutic interventions for diabetic and heart failure patients.
- To delineate the mechanisms that link perturbations in metabolism and metabolic intermediates to cellular signaling and epigenetic regulation.
- To provide an environment for collaborative research, both within the lab and the larger scientific community while fostering the training and professional development needed for our team to progress in their individual career goals.
The primary goal of the R01-funded research in the laboratory is to determine the role of glucose fluctuations in the regulation of DNA methylation in transgenic models of glucose uptake and signaling related to diabetes; additionally, one family of kinases that regulate mitochondrial substrate selection and utilization (i.e., PDK) 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). Other projects in the laboratory include determining the role of the protein post-translational modification O-GlcNAc in regulating cardiac cellular function.
Together these studies define the role that changes in glucose levels have on long-lasting epigenetic regulation of gene expression in a process termed “glycemic memory”.
Recent studies include work defining epigenetic pathways in human heart failure biopsies to determine etiology-specific epigenetic signatures including differences by ischemia and race. By determining these molecular signatures of altered protein regulation and DNA structure/regulation we aim to provide critical knowledge to determining future therapeutic interventions for diabetic and heart failure patients.