Jianxin Sun, PhD
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Dr. Sun’s laboratory has the following two major research interests:
- Molecular mechanisms of vascular inflammation
- Regulation of endothelia nitric oxide synthase expression and activity
Molecular mechanisms of vascular inflammation
Vascular inflammation plays an important role in the development and progression of cardiovascular diseases such as atherosclerosis and diabetic vascular complications. Recently, we identified several molecules, including orphan nuclear receptor Nur77, in vascular endothelial cells that are rapidly induced in response to inflammatory stimuli, such as Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and lipopolysaccharide (LPS). Preliminary results suggest that nuclear orphan receptor Nur77 exerts potent anti-inflammatory effects in human endothelial cells via an up-regulation of IkBα expression, thus constitutes a negative feedback mechanism in inhibiting vascular inflammation. However, the role of endogenous Nur77 in IkB expression and NF-kB activation in endothelial cells (ECs) remains to be determined. In addition, the transcriptional targets of Nur77 are largely unknown and will be further investigated by genomics and proteomics in ECs and macrophages. Furthermore, the effect of Nur77 genetic deletion on the development of cardiovascular diseases will be assessed in murine models of atherosclerosis, cardiac hypertrophy and heart failure.
Regulation of endothelia nitric oxide synthase expression and activity
Endothelium-derived nitric oxide (NO) is an important regulator of vascular function. NO is produced by endothelial NO synthase (eNOS) whose expression is modulated, in part, at posttranscriptional levels. To elucidate the molecular basis of TNF-α-mediated posttranscriptional control via mRNA stabilization, eNOS 3' untranslated region (3'-UTR) binding proteins were purified by RNA affinity chromatography from a cytosolic fraction of TNF-α stimulated human umbilical vein endothelial cells (HUVECs) and identified by proteomic methods in the laboratory. We, for the first time, found that translation elongation factor 1-alpha 1 (eEF1A1) is a novel trans-acting factor that binds to eNOS mRNA in response to TNF-α stimulation. The interaction of eEF1A1 with eNOS 3'-UTR was demonstrated by RNA gel mobility shift and UV cross-linking assays. The functional significance of eEF1A1 in the regulation of eNOS mRNA stability was confirmed by eEF1A1 gene over-expression and siRNA mediated gene knockdown in endothelial cells. We are generating dominant negative eEF1A1 and cell permeable peptides derived from eNOS mRNA binding motif in eEF1A1 to investigate the in vivo functional significance in the regulation of vascular homeostasis. In addition, we will continue to identify the 3'-UTR ribonucleoprotein complexes by mass spectrometry and study their roles in the regulation of eNOS mRNA stability and their involvements in the endothelial dysfunction associated with many cardiovascular diseases.
Check out Dr. Sun’s publications and funded research projects