ERG Is a member of the ETS transcription factor family that has recently been shown to participate in the regulafion of selected endothelial-restricted genes including vWF, endoglin, and VE-cadherin. Our preliminary studies demonstrate several unique features of ERG. First, ERG exhibits a highly endothelial cell (EC)-restricted expression pattern throughout vascular development and in several adult fissues. Second, during embryonic stem (ES) cell differenfiafion, ERG is first expressed in a subset of VEGF-R2+ cells that also express VE-cadherin. Third, ERG closely tracks with stem cells that differentiate along the endothelial lineage. Fourth, downregulafion of ERG in ES cells markedly inhibits EC differenfiafion and vascular structure formation in embryoid bodies (EB). The overall hypothesis for this proposal is that ERG is a critical transcriptional regulator of EC differentiation and vascular development.
Aim I will define the role of ERG during vascular development. ERG is expressed in an EC-restricted pattern within several tissues and organs during early stages of vascular development. The hypothesis for this aim is that ERG expression is required for vascular development.
Aim II will define the transcriptional and epigenefic regulafion of endothelial differenfiafion by ERG The hypothesis for this aim is that ERG funcfions at mulfiple levels to regulate EC differentiation. ERG may act alone or in combinafion with other transcription factors to regulate EC-specific target genes such as VE-cadherin.
Aim III will examine the role of ERG in regulafing EPC function and postnatal vasculogenesis Endothelial progenitor cells (EPC) represent an important cell type that can promote vascular repair, angiogenesis and post-natal vasculogenesis. The hypothesis for this aim is that ERG is a critical transcriptional regulator of EPC function and post-natal vasculogenesis.
The transcriptional regulation of EC differentiation remains pooriy understood. This proposal is significant in that we believe we have identified ERG as a critical transcriptional regulator of EC differentiation. EC differentiation is a developmental process that is recapitulated under pathologic conditions such as coronary and limb ischemia to promote angiogenesis and post-natal vasculogenesis. The identification of specific transcription factors such as ERG that regulate EC differentiation will not only enhance our basic understanding of early stages of EC differentiation and vascular development but may also lead to the development of novel therapeutic approaches of enhancing the process of tissue revascularization in patients with ischemic heart and/or peripheral vascular disease.
|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-1Î± 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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