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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076540-09
Application #
8511783
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
9
Fiscal Year
2013
Total Cost
$337,007
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Yuan, Lei; Chan, Gary C; Beeler, David et al. (2016) A role of stochastic phenotype switching in generating mosaic endothelial cell heterogeneity. Nat Commun 7:10160
Bai, Aiping; Robson, Simon (2015) Beyond ecto-nucleotidase: CD39 defines human Th17 cells with CD161. Purinergic Signal 11:317-9
Bai, Aiping; Moss, Alan; Rothweiler, Sonja et al. (2015) NADH oxidase-dependent CD39 expression by CD8(+) T cells modulates interferon gamma responses via generation of adenosine. Nat Commun 6:8819
Bai, A; Kokkotou, E; Zheng, Y et al. (2015) Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses. Cell Death Dis 6:e1828
Yan, Matthew S; Marsden, Philip A (2015) Epigenetics in the Vascular Endothelium: Looking From a Different Perspective in the Epigenomics Era. Arterioscler Thromb Vasc Biol 35:2297-306
Bai, Aiping; Moss, Alan; Kokkotou, Efi et al. (2014) CD39 and CD161 modulate Th17 responses in Crohn's disease. J Immunol 193:3366-77
Aird, William C; Mosnier, Laurent O; Fairhurst, Rick M (2014) Plasmodium falciparum picks (on) EPCR. Blood 123:163-7
Rowe, Glenn C; Raghuram, Srilatha; Jang, Cholsoon et al. (2014) PGC-1α induces SPP1 to activate macrophages and orchestrate functional angiogenesis in skeletal muscle. Circ Res 115:504-17
Turgeon, Paul J; Sukumar, Aravin N; Marsden, Philip A (2014) Epigenetics of Cardiovascular Disease - A New ""Beat"" in Coronary Artery Disease. Med Epigenet 2:37-52
Bian, Shu; Sun, Xiaofeng; Bai, Aiping et al. (2013) P2X7 integrates PI3K/AKT and AMPK-PRAS40-mTOR signaling pathways to mediate tumor cell death. PLoS One 8:e60184

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