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LIPID MEDIATORS in HEALTH and DISEASE II: from the Cutting Edge–A Tribute to Edward Dennis and 7TH INTERNATIONAL CONFERENCE on PHOSPHOLIPASE A2 and LIPID MEDIATORS

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LIPID MEDIATORS in HEALTH and DISEASE II: from the Cutting Edge–A Tribute to Edward Dennis and 7TH INTERNATIONAL CONFERENCE on PHOSPHOLIPASE A2 and LIPID MEDIATORS LIPID MEDIATORS IN HEALTH AND DISEASE II: From The Cutting Edge–A Tribute to Edward Dennis And 7TH INTERNATIONAL CONFERENCE ON PHOSPHOLIPASE A2 and LIPID MEDIATORS: From Bench To Translational Medicine Honorary Chair: Nobel Laureate Bengt Samuelsson La Jolla, California May 19-20, 2016 http://www.medschool.lsuhsc.edu/neuroscience/LipidMediatorsPLA2-2016/ Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis 2+ Steered molecular dynamics simulation of Group VIA Ca - independent phospholipase A2 (PLA2) embedded in a bilayer membrane composed mainly of 1-palmitoyl, 2-oleoyl phosphatidycholine (POPC) extracting and pulling a 1-palmitoyl, 2-archidonyl phosphatidylcholine (PAPC) into its binding pocket in the active site. [For movies of this simulation, see Mouchlis VD, Bucher, D, McCammon, JA, Dennia EA (2015) Membranes serve as allosteric activators of phospholipase A2 enabling it to extract, bind, and hydrolyze phospholipid substrates, Proc Natl Acad Sci U S A, 112, E516-25.] Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis WELCOME I would like to welcome all of the participants of the Lipid Mediators in Health and Disease II: From The Cutting Edge, A Tribute to Edward Dennis, and the 7th International Conference on Phospholipase A2 and Lipid Mediators: From Bench To Translational Medicine. This conference follows upon the very successful meeting led by Professor Jesper Z. Haeggström at the Karolinska Institutet, Nobel Forum, Stockholm, Sweden, on August 27-29, 2014, where Nobel Laureate Professor Bengt Samuelsson was honored. Lipids serve a myriad of essential functions in cell signaling, cell organization, energy metabolism, and overall homeostasis. They are also precursors for the biosynthesis of potent chemical mediators of the immune, nervous, and endocrine systems. Lipids are central mediators of paracrine and autocrine signaling pathways and networks with critical roles in health and the major diseases of our times. Phospholipase A2 is the key enzyme that initiates the inflammatory cascade by the release of arachidonic acid to generate numerous lipid mediators, including eicosanoids and docosanoids. Other enzymes generate endocannabinoids, platelet activating factor, sphingosines, and steroid hormones. Numerous successful drugs have emanated from insights into the role of these signaling cascades in pathogenesis. The field of lipid mediators is vibrant, as attested to in this conference by the lectures and posters presented that are relevant to fundamental biology as well as to clinical research and therapeutic opportunities. The mission of this conference is to bring together the world’s leading experts on cutting-edge topics, exchange new concepts and advances, as well as identify new paths and future strategies. I want to thank, in a very special way, the members of the organizing committee, as well as the speakers and chairpersons for the contributions they already made toward this conference. I would especially like to thank the sponsors, who saw the worthiness of this conference, for their contributions and support. And finally I would like to thank Edward Dennis, for whom this conference is paying tribute, for all of his remarkable contributions to the field of lipids. With wishes for a memorable scientific meeting! Nicolas G. Bazan, MD, PhD Conference Chair and Organizer 1 Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis LIPID MEDIATORS IN HEALTH AND DISEASE II: From The Cutting Edge A Tribute to Edward Dennis And 7TH INTERNATIONAL CONFERENCE ON PHOSPHOLIPASE A2 and LIPID MEDIATORS: From Bench To Translational Medicine Honorary Chair: Nobel Laureate Dr. Bengt Samuelsson (Karolinska Institutet, Stockholm, Sweden) Nicolas G. Bazan, MD, PhD, Louisiana State University Health New Orleans, School of Medicine (New Orleans, LA, USA), Conference Chair and Organizer Jerold Chun, MD, PhD, The Scripps Research Institute, (La Jolla, CA, USA) Jesper Z. Haeggström, MD, PhD, Karolinska lnstitutet (Stockholm, Sweden) Timothy Hla, PhD, Weill Cornell Medical College, (New York, NY, USA) Charles N. Serhan, PhD, DSc, Harvard Medical School (Boston, MA, USA) Takao Shimizu, MD, PhD, University of Tokyo, (Tokyo Japan) Venue: Scripps Forum University of California, San Diego La Jolla, California Louisiana State University Health New Orleans, School of Medicine, Neuroscience Center of Excellence 2020 Gravier Street, 8th Floor, New Orleans, Louisiana 70112 Email: [email protected]; FAX (504) 568-5801 2 Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis PROGRAM SCRIPPS SEASIDE FORUM LA JOLLA, CALIFORNIA, MAY 19-20, 2016 CONTENTS Welcome Letter .............................................................................................................. 1 Program Cover/Organizing Committee .......................................................................... 2 A Tribute to Ed Dennis ................................................................................................... 4-6 Sponsors ........................................................................................................................ 7 Overall Program ............................................................................................................. 9-11 Keynote Lecture Bengt Samuelsson ............................................................................................ 13 2016 Journal of Lipid Research Lecture Jesper Z. Haeggström ....................................................................................... 27 Lightning talks selected from posters ............................................................................ 43-52 2016 Journal of Lipid Research Junior Investigator Award Emma Börgeson ............................................................................................... 43 Posters .......................................................................................................................... 89-152 Participant List .............................................................................................................. 153-166 Maps & Useful Information ........................................................................................... 167-169 3 Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis Edward A. Dennis’ Contributions to Science Ed and his laboratory have made fundamental contributions to several aspects of the phospholipase A2 (PLA2) superfamily over the last 45 years. His first major contribution was his hypothesis of “surface dilution kinetics” in the early 1970s. This concept interprets structural and mechanistic studies on PLA2 and other enzymes acting on membranes and other lipid- water interfaces. As his understanding of phospholipases advanced, he realized that lipids released by these enzymes are information- containing signaling molecules. In the 1980s, he recognized that phospholipase A2 regulates the generation of precursors for the biosynthesis of eicosanoids and other bioactive lipid mediators of inflammation underlying disease progression. When Ed started his independent faculty position at the University of California, San Diego in 1970, the central role of lipids in energy storage and metabolism was central in biology, and the structural role of lipids in biological membranes was assumed. At the time, the scientific community was focused on nucleic acids, proteins, and carbohydrates as information-containing molecules. Ed hypothesized that the enzymes that act on lipid substrates residing in or on membranes and micelles have important signaling roles and display unique modes of action differing from those acting on water soluble substrates. This led him to create the concept of “surface dilution kinetics” in 1973. Then, his laboratory hypothesized that PLA2 contains allosteric activator sites for specific phospholipids based on observing activation of PLA2 by certain specific phospholipids. Through NMR studies and x-ray crystallography, he could later identify the specific site on PLA2 responsible for the activation. During the last decade, his laboratory developed the application of deuterium exchange mass spectrometry (DXMS) to further understand the nature of interfacial activation for enzymes acting on membranes and micelles. This led him to an increased use of molecular dynamic approaches to propose and prove the allosteric activation of PLA2 by membranes. Most recently his lab determined the catalytic cycle of two different human PLA2s, namely cPLA2 and iPLA2, which were only purified in the early 1990s. Especially notable was the purification by his lab of the Group VIA iPLA2 reported in 1994. His lab also introduced computer-aided techniques guided by DXMS for studying membrane interactions allowing for the creation of structural complexes of each enzyme with a single phospholipid substrate molecule. Simulations of the enzyme–substrate-membrane system revealed important information about the mechanisms by which these enzymes associate with the membrane and then extract and bind their phospholipid substrate. Most 4 Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis strikingly, his laboratory demonstrated that the membrane acts as an allosteric ligand that binds the enzyme’s interfacial surface, shifting its conformation from a closed (inactive) state in water to an open (active) state at the membrane
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