A long term goal of my laboratory is to understand mechanisms by which G protein-coupled receptor (GPCR) signaling leads to vascular inflammation, atherosclerosis, and thrombosis. Two major research programs are currently under investigation. One research program focuses on the role of P2Y2 receptor, an ATP/UTP-sensitive nucleotide receptor, in promoting pro-thrombotic gene expression such as the tissue factor gene, and its participation in inflammation-induced thrombosis.
A second area focuses on a chemokine receptor termed CXCR7. We are trying to understand how CXCR7 is induced during monocyte-to-macrophage differentiation and its significance in cell signaling and in promoting vascular inflammation and atherosclerosis. All research projects rely heavily on molecular biology, biochemical, and pharmacological methods in cultured vascular endothelial cells and blood monocytes/macrophages. Genetic approaches like new mouse models with endothelial cell-specific and myeloid cells-targeted deletion of the P2Y2 receptor or CXCR7 genes are also employed for in vivo study. An overriding objective of the research programs is to identify novel molecular targets for anti-inflammation therapy with a focus on cardiovascular diseases such as atherosclerosis.
1. Ma W, Liu Y, Wang C, Zhang L, Crocker L, Shen J. Atorvastatin Inhibits CXCR7 Induction to Reduce Macrophage Migration. Biochem Pharmacol. 2014;89(1):99-108.
2. Ma W, Liu Y, Ellison N, Shen J. Induction of C-X-C Chemokine Receptor Type 7 (CXCR7) Switches Stromal Cell-Derived Factor-1 (SDF-1) Signaling and Phagocytic Activity in Macrophages Linked to Atherosclerosis. J Biol Chem. 2013, 288(22):15481-15494.
3. Shen J, Ma W, Liu Y. Deacetylase SIRT6 Deaccelerates Endothelial Senescence. Cardiovasc Res. 2013, 97(3): 391-392. (Invited editorial)
4. Ding L, Ma W, Littmann T, Camp R, Shen J. The P2Y2 Nucleotide Receptor Mediates Tissue Factor Expression in Human Coronary Artery Endothelial Cells. J Biol Chem. 2011, 286(30):27027-27038.
5. Shen J, Chandrasekharan UM, Ashraf MZ, Long E, Morton RE, Liu Y, Smith JD, DiCorleto PE. Lack of MAP Kinase Phosphatase-1 Protects ApoE-null Mice against Atherosclerosis. Circ Res. 2010;106(5):902-910.
6. Shen J and DiCorleto PE. Adenosine Prompts the Heart to Recruit Endothelial Progenitors. Circ Res. 2008;102(3):280-282.
7. Shen J and DiCorleto PE. ADP stimulates human endothelial cell migration via P2Y1 nucleotide receptor-mediated mitogen-activated protein kinase pathways. Circ Res. 2008;102(4):448-456.
8. Shen J, Halenda SP, Sturek M, Wilden PA. Novel mitogenic effect of adenosine on coronary artery smooth muscle cells: role for the A1 adenosine receptor. Circ Res. 2005;96(9):982-990.
9. Shen J, Seye CI, Wang M, Weisman GA, Wilden PA, Sturek M. Cloning, up-regulation, and mitogenic role of porcine P2Y2 receptor in coronary artery smooth muscle cells. Mol Pharmacol. 2004; 66(5):1265-1274.