The primary goal of the Epigenetics Core (Core B) is to provide each project leader and their team access to our knowledge, resources, and technical support for dissecting apart the epigenetic events that are responsible for the proper temporal and spatial differentiation of endothelial cells (ECs). The core has developed and implemented the techniques that are required for each project leader to be successful. Each investigator will be provided with the necessary protocols and technical training to carry out their experiments. For example, we will help each investigator's team establish optimal ChlP conditions for the ChlP-chip experiments. The core will provide the necessary controls and help with the optimization, hybridizations, and analysis of tiling microarrays. Our longstanding relationship with the Bioinformatics and Information Science Center at Western Kentucky University will facilitate rapid analysis of the data generated by these approaches. The core will also provide technical support and quantitative real-time PCR machines for the high resolution ChlP validation of previously identified target genes as well as the newly discovered gene targets involved in EC differentiation. The core is currently using high density microarrays from Roche/NimbleGen for expression and ChlP-chip. We are also using Agilent/lnvitrogen non-coding microarrays {i.e., Long Non-coding and MicroRNAs). These genomic approaches have allowed us to identify the coding and non-coding targets that are downstream of histone demethylases. The observations from our studies will inevitably provide valuable insights into the questions being asked in this program project. The ultimate goal of this core is to provide technical and scientific oversight for the discovery oif epigenetic mechanisms regulating endothelial biology;to facilitate rapid development and interpretation of genome-wide experiments;and to integrate our overall interest in histone modification dynamics with understanding the molecular mechanisms regulating endothelial cell fate and differentiation in human health and disease.

Public Health Relevance

The overall significance of this core is to provide valuable technical expertise, scientific insight, and wealth of resources in the area of epigenetics so that novel molecular mechanisms that govern the heterogeneity of ECs in health and disease will be discovered.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Beth Israel Deaconess Medical Center
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