FASEB SRC on Lysophospholipd Mediators in Health and Disease


Principal Investigator: Julie D Saba
Abstract: DESCRIPTION (provided by applicant): The 6th FASEB Summer Research Conference on "Lysophospholipid Mediators in Health and Disease" will be held August 14-19, 2011 in Lucca, Italy. This conference will address current concepts in the rapidly developing field of lysphospholipid-mediated signaling and related biology. The lysophospholipids sphingosine- 1-phosphate (S1P) and lysophosphatidic acid (LPA) are bioactive lipids generated via catabolism of membrane sphingolipids (S1P) and phospholipids (LPA). They signal through a family of ubiquitously expressed cell surface receptors, formerly called the Endothelial Differentiation Gene (EDG) receptors. Lysophospholipids mediate a plethora of physiological and pathological activities via interactions with their high-affinity G protein- coupled receptors, as well as through recently revealed receptor-independent intracellular mechanisms. LPA and S1P regulate chemotaxis, stress responses, cytoskeletal organization, calcium signaling, cell survival, apoptosis, autophagy, and gene transcription. Lysophospholipid signaling events also contribute to complex physiological and developmental processes including angiogenesis, lymphocyte trafficking and the migration of hematopoietic stem cells, natural killer cells, and cancer cells. Importantly, lysophospholipids play critical roles in carcinogenesis and cancer progression. Enzymes responsible for catalyzing S1P and LPA formation including autotaxin (the principal enzyme responsible for generating LPA) and sphingosine kinase 1 (which generates S1P) are bona fide oncogenes that promote transformation in model systems, are aberrantly expressed in many human cancers, and serve as biomarkers of prognostic significance. Alterations in lysophospholipid metabolism and signaling also contribute to drug and radiation resistance, tumor angiogenesis, and progression of many cancer types including ovarian, breast, prostate, thyroid, colon, brain and hematological malignancies. Further, recent studies indicate that S1P is a nuclear regulator of epigenetic transcriptional control. Tremendous progress has been made in targeting autotaxin, sphingosine kinase and lysophospholipids themselves as novel therapeutic strategies in cancer. Due to the rapid pace of discovery in this field, this biennial conference is essential to achieving maximal translational potential through cross- pollination of ideas, sharing of new reagents and initiation of collaborations between academic scientists, industry and clinician scientists. Toward that end, our specific aims are to: 1) convene an internationally recognized group of investigators to present and discuss novel findings regarding lysophospholipid metabolism, signaling, regulation, pharmacology and clinical trials;2) to facilitate participation of early career investigators;3) to promote participation of women and underrepresented minorities. The program includes oral and poster presentation sessions whose themes cover a range of topics including lysophospholipid biochemistry and signaling, pharmacology, and the role of lysophospholipids in disease. In addition, a new Meet the Experts session will facilitate interactions between early career and established scientists in the field. PUBLIC HEALTH RELEVANCE: This is a proposal to support the convening of the 2011 biannual Federation of American Societies for Experimental Biology Summer Research Conference on Lysophospholipid Mediators in Health and Disease. The meeting will bring together an international group of scientists at all career stages to share the most recent and exciting scientific findings regarding two lipid signaling molecules which share a common family of cell surface receptors through which they modulate cell biology and physiological responses. The effects of lysophospholipid signaling are important in the pathophysiology of cancer, cardiovascular disease, immunology, neurology and infectious disease, and key components of these pathways are being targeted for therapeutic purposes. Women, underrepresented minorities and early stage investigators will play an important role in the conference as speakers, chairs, poster presenters and will have opportunities to interact with others through discussions, Meet the Expert and Meet the Editor sessions.
Funding Period: 2011-08-12 - 2012-08-11
more information: NIH RePORT