Andrew J Morris

..We review the mechanisms controlling the production, metabolism, and distribution of these lipids between vascular cells, circulating blood components, and the plasma...

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..To determine whether LPA contributes to remodeling of the pulmonary vasculature, we examined responses in mice with alterations in LPA signaling and metabolism...

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..Integrin binding therefore localizes ATX activity to the cell surface, providing a mechanism to generate LPA in the vicinity of its receptors...

..Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P...

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..These results identify a role for LPA1 and LPA2 in regulating SMC migratory responses in the context of vascular injury but suggest that additional LPA receptor subtypes are required for other LPA-mediated effects in the vasculature...

..In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation...

..These two functions are necessary for full expression of the biological activity of the protein in intracellular lipid metabolism and transcriptional control of adipogenesis...

..The aim of the present study was to determine whether GV sPLA(2)-hydrolyzed LDL (GV-LDL) produces pro-atherogenic effects in macrophages independent of cholesterol accumulation...

..Taken together, these results focus attention on integral membrane lipid phosphatases as regulators of isoprenoid phosphate metabolism and suggest that PDP1/PPAPDC2 is a functional isoprenoid diphosphate phosphatase...

..LPA is present in blood and exposure or release of LPA after atherosclerotic plaque rupture has been proposed to trigger platelet thrombus formation...

..This chapter describes methods for determining the activity of recombinant autotaxin/lysoPLD using radiolabeled and fluorogenic substrates...

..Our data implicate A?/J?-NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs...

..Thus, the LPA-rich environment of the ovarian cancer cell in vivo and the subsequent effects of cellular pathophysiology may be a consequence of both increased LPA production and decreased LPA metabolism by ovarian cancer cells...

..We describe the use of both radiolabeled and fluorescent lipid substrates for the detection, quantitation and analysis of the enzymatic activities of the LPPs measured using intact or broken cell preparations as the source of enzyme...

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..Our results identify a novel role for nucleotides in the regulation of ovarian cancer cells and suggest an indirect but critical function for PLD2 in agonist-stimulated LPA production...

..Thus genetic or pharmacological manipulation of LPA metabolism, receptor activation, or downstream signaling is an attractive approach for therapy of ovarian cancer...

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..Successful completion of the research will provide the framework and impetus to develop novel effective therapeutics for ovarian cancer. ..

..Resolution of the interrelated issues outlined above is central to this goal because it will ultimately lead to the design of pharmacological and genetic strategies to manipulate LPA signaling in vivo. ..

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..For the past 10 years this field has generated about 2000 peer reviewed research publications each year. The funds requested in this proposal will make an invaluable contribution to the support of this conference. ..

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