Description of Research Expertise

Research Summary:

Prostanoids, a family of lipid mediators with multiple and diverse biological actions, are formed by the action of cyclooxygenase (COX) on arachidonic acid. A single gene product, encoding a G protein coupled receptor (GPCR) has been identified for prostacyclin (the IP), PGF2α (the FP) and TxA2 (the TP), while four distinct GPCRs for PGE2 (the EP1-4), and two for PGD2 (DP1 and DP2), have been cloned.

Our laboratory is interested in the novel pathways directing the function and regulation of prostanoid receptors. Over the past decade the paradigm of GPCR homo- and hetero- dimerization has become and accepted phenomenon. We have show dimerization of IP and TP to form homo- and hetero- dimers with consequent changes in TP signaling and regulation. More recently we have identified formation of DP1 and DP2 homo- and hetero- dimers (but not IP-DP heterodimers) at comparable affinities. Currently we are investigating the molecular and cellular events that regulate prostanoid receptor dimerization in normal settings and cardiovascular disease.

A second major resarch focus of our laboratory emerged from the recent interest in the inducible COX-2 isoform and it partner in PGE2 generation, mPGES-1, as a chemopreventative or chemotherapeutic target in human cancer. Epidemiological reports demonstrate a reduction in the risk of mammary cancer with co-incident used of COX inhibitors. Our research examines the role of COX-1 and COX-2, in mammary cancer, and cancer related thrombosis, using mice engineered to lack specifically COX-2 or mPGES-1 expression the mammary epitheilium or in macrophages. Inititation, progression and metastasis of mammary tumors, and the incidence of cancer-related thrombosis, is currently under examination.