Maurice, Donald H - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

The Maurice Lab is interested in investigating the role of cyclic nucleotide (cAMP and cGMP) compartmentation and cyclic nucleotide signaling in human vascular cells including arterial endothelial cells and arterial smooth muscle cells. Since virtually all cells are either directly or indirectly influenced by cAMP and or cGMP, this system represents a potential therapeutic target in multiple cardiovascular diseases such as atherosclerosis and restenosis, and is important processes such as angiogenesis. Further information available at MauriceLab.com

研究领域

In most tissues, cyclic nucleotides (cAMP and cGMP) act as second messengers to mediate the effects of physiologic and pharmacologic agents. In the cardiovascular system, both cAMP and cGMP are involved in regulating cardiac muscle and vascular smooth muscle contractility and growth. Unregulated cardiac and vascular muscle contractility or growth are involved in many cardiovascular diseases (congestive heart failure, hypertension, stroke and atherosclerosis). Studies in progress in this laboratory focus on the molecular basis of cyclic nucleotide-mediated effects in vascular tissues. More specifically, we study the enzymes that synthesise cAMP and cGMP (adenylyl cyclase and guanylyl cyclase) and those which catabolically inactivate these two second messengers (cyclic nucleotide phosphodiesterases) using two parallel and complementary approaches. Firstly, cloning of these enzymes from heart and aorta, and expression of the recombinant enzymes, allows for detailed analysis of the structure, function, level of expression and relative abundance of these enzymes in these tissues. Secondly, we are studying cAMP and cGMP metabolism in cultured vascular smooth muscle and vascular endothelial cell systems. With these culture systems, the control of the level of the cyclic nucleotides by the endogenous enzymes or by transiently expressed recombinant enzymes and the resultant effect on cell growth and differentiation can be assessed. Combined, these approaches allow us to study nucleotide-mediated signalling both at a molecular as well as a cellular level.

近期论文

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Wilson LS, Elbatarny HS, Crawley SW, Bennett BM and Maurice DH, 2008, Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Proc Natl Acad Sci USA, 105:13650-13655. Raymond DR, Wilson LS, Carter RL and Maurice DH, 2007, Numerous distinct PKA- or EPAC-based signalling complexes allow selective phosphodiestaerase 3 and phosphodiesterase 4 coordination of cell adhesion. Cell Signal, 19:2507-2518. Netherton SJ, Sutton JA, Wilson LS, Carter RL and Maurice DH, 2007, Both protein kinase A and exchange protein activated by cAMP coordinate adhesion of human vascular endothelial cells. Circ Res, 101:768-776. Houslay MD, Baillie GS and Maurice DH, 2007, cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalized cAMP signaling. Circ Res, 100:950-966. Palmer D, Jimmo SL, Raymond DR, Wilson LS, Carter RL and Maurice DH, 2007, Protein kinase A phosphorylation of human phosphodiesterase 3B promotes 14-3-3 protein binding and inhibits phosphatase-catalyzed inactivation. J Biol Chem, 282:9411-9419. Elbatarny HS, Netherton SJ, Ovens JD, Ferguson AV and Maurice DH, 2007, Adiponectin, ghrelin and leptin differentially influence human platelet and human vascular endothelial cell functions: implication in obesity-associated cardiovascular diseases. Eur J Pharmacol, 558:7-13. Netherton SJ and Maurice DH, 2005, Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: implications in angiogenesis. Mol Pharmacol, 67:263-272. Tilley DG and Maurice DH, 2005, Vascular smooth muscle cell phenotype-dependent phosphodiesterase 4D short form expression: role of differential histone acetylation on cAMP-regulated function. Mol Pharmacol, 68:596-605. Elbatarny HS and Maurice DH, 2005, Leptin-mediated activation of human platelets: involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex. Am J Physiol Endocrinol Metab, 289:E695-E702. Maurice DH, Palmer D, Tilley DG, Dunkerley HA, Netherton SJ, Raymond DR, Elbatarny HS and Jimmo SL, 2003, Cyclic nucleotide phosphodiesterase activity, expression and targeting in cells of the cardiovascular system. Mol Pharmacol, 64:533-546.