The purinergic receptor theory was proposed 30 years ago by Dr. Burnstock. Since then, the roles of extracellular nucleotides and their receptors have received tremendous attention. To date, eight G protein-coupled P2Y nucleotide receptors and four adenosine receptors have been cloned and pharmacologically characterized. Although extracellular nucleotides/nucleosides, in particular ATP/adenosine, are well-established signaling molecules in the regulation of the vascular tone, their roles in the development of vascular diseases gained attention only recently. One of my long-term research objectives in the area of cardiovascular science is to use pharmacological, physiological, biochemical, and molecular biological approaches including transgenic mice to reveal the big picture of purinergic control of vascular functions. My research emphasis in this field will be on receptor signaling, function and regulation in the context of vascular cell culture and various disease models, including atherosclerosis, vascular restenosis and angiogenesis.
My second research focus is concerning the role of MAP kinase phosphatase-1 (MKP-1) in cardiovascular remodeling. During the course I studied the role of MKP-1 in atherosclerosis, I unexpectedly observed that genetic deletion (knockout) of the MKP-1 gene in mice affects body weight and heart weight in an opposite direction. This is a very exciting finding, because it suggests that MKP-1 may play important role(s) in obesity and cardiac remodeling. Ongoing work in my Lab is to investigate the role of MKP-1 in cardiac and vascular hypertrophy using MKP-1-knockout mice.
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. [*corresponding authorship]
Shen J, Chandrasekharan UM, Ashraf MZ, Long E, Morton RE, Liu Y, Smith JD, DiCorleto PE. Lack of mitogen-activated protein kinase phosphatase-1 protects ApoE-null mice against atherosclerosis. Circ Res. 2010;106(5):902-910.
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.
Shen J* and DiCorleto PE. Adenosine prompts the heart to recruit endothelial progenitors. Circ Res. 2008; 102 (3): 280-282. [*Invited editorial & corresponding authorship]