LIPID MAPS

Welcome & Introduction

Edward A. DennisDepartments of Pharmacology and Chemistry/Biochemistry

University of California, San Diego LIPID MAPS

TM

LIPDOMICS WORKSHOP

LIPID MAPSLIPID MAPSLipidLipid MMetabolites etabolites AAnd nd PPathways athways SStrategytrategy

GENOMICSGENOMICS (TRANSCRIPTOMICS) (TRANSCRIPTOMICS)

PROTEOMICSPROTEOMICS

METABOLOMICSMETABOLOMICS

““LIPIDOMICSLIPIDOMICS””LIPID MAPS

TM

LIPID MAPSLIPID MAPSLipidLipid MMetabolites etabolites AAnd nd PPathways athways SStrategytrategy

GENOMICSGENOMICS (TRANSCRIPTOMICS) (TRANSCRIPTOMICS)

PROTEOMICSPROTEOMICS

METABOLOMICSMETABOLOMICS

““LIPIDOMICSLIPIDOMICS””

4 base side chains4 base side chains

20 amino acid side chains20 amino acid side chains

nucleic acids, amino acids,nucleic acids, amino acids,sugars and fats: sugars and fats: >10>105 5 ??

all the fats: >10all the fats: >105 5 ??TM

LIPID MAPS

TM

“Lipidomics Joins the Omics Evolution” Dennis (2009) PNAS 106, 2089

LIPID MAPS HYPOTHESIS

A systems biology approach to identify the manythousands of lipid molecular species in cells andtheir quantitative changes in response to cellularstress and challenge will lead us to newmethodologies for monitoring lipid changes, andthis in turn will lead to breakthroughs in theunderstanding and treatment of lipid baseddiseases.

LIPID MAPS

TM

LIPID MAPSLIPID MAPS

NIGMS Large Scale Collaborative GrantNIGMS Large Scale Collaborative Grant““Glue GrantGlue Grant”” [ [NIH U54 GM 69338]

Mouse Macrophage:Mouse Macrophage: RAWRAW cell line & primary cellcell line & primary cellEnvironmental Agonist:Environmental Agonist: initially LPS, then oxidized LDLinitially LPS, then oxidized LDL

HPLC/Mass Spectrometer:HPLC/Mass Spectrometer: identify known & new, quantifyidentify known & new, quantifySynthesis/Characterize:Synthesis/Characterize: new ones, MS quantitative standardsnew ones, MS quantitative standards

Bioinformatics:Bioinformatics: informatics and lipid networksinformatics and lipid networksWebsite:Website: LIPID MAPS/Nature Lipidomics Gateway

http://www.lipidmaps.orghttp://www.lipidmaps.org

LIPID MAPS

TM

LIPID MAPS CORES LIPID MAPS CORES

BioinformaticsBioinformatics

GlycerolipidsGlycerolipids

Prenols/Structural LipidomicsPrenols/Structural LipidomicsSterolsSterols

Fatty Acyls/EicosanoidsFatty Acyls/Eicosanoids

GlycerophospholipidsGlycerophospholipids Sphingolipids/GangliosidesSphingolipids/Gangliosides

Lipid Synthesis/CharacterizationLipid Synthesis/CharacterizationMichael VanNieuwenhze - Michael VanNieuwenhze - UCSDUCSDWalter Shaw -Walter Shaw - Avanti Polar Lipids Avanti Polar Lipids

Shankar Subramaniam - Shankar Subramaniam - UCSDUCSD

Robert C. Murphy - Robert C. Murphy - ColoradoColorado

Christian Raetz - Christian Raetz - DukeDukeDavid W. Russell - David W. Russell - UTSWUTSW

Alfred H. Merrill - Alfred H. Merrill - Georgia TechGeorgia TechH. Alex Brown -H. Alex Brown - Vanderbilt Vanderbilt

Macrophage BiologyMacrophage BiologyChristopher Glass - Christopher Glass - UCSDUCSD

Edward A. Dennis - UCSDEdward A. Dennis - UCSD

LC/Mass SpecLC/Mass SpecRobert C. Murphy Robert C. Murphy –– ColoradoColorado

Nicholas Winograd Nicholas Winograd –– Penn State Penn State

PIPI Edward A. Dennis - Edward A. Dennis - UCSDUCSD

TM TM

LIPID MAPS

LIPID MAPS

TMOxidized Lipids Bridge Joe Witztum - UCSD

Nuclei – DAPIMitochondria – MitoTracker Red

Kdo2 Lipid A (LPS species) A Specific Agonist of TLR-4on RAW 264.7 macrophages

LIPID MAPS

TM

Raetz et al [2006] JLR 47. 1097-1111

HOOH

OOH

O

Arachidonic Acid

15 LO15 LO

HETEsHETEs

15(S)HETE15(S)HETE

COX

ProstaglandinsProstaglandins

PGEPGE22

14,15-EET

P450Epoxyeicosatrienoids

5 LO5 LO

LeukotrienesLeukotrienes

LTBLTB44

OH

O

OH

OH

O

OH

O

O

OHH OHH

OH

O

LIPID MAPS

TM

5-LOX

12-LOXCYP(EET)

15-LOX

Buczynski et. al. JLR 50, 1015-38 (2009)

COX CYP(ω)

EICOSANOIDS LIPID MAPS

TM

LIPID MAPS

TM

LIPID MAPS

TM

Classification, Nomenclature, StructureJ. Lipid Research (2005) 46, 839-862 ; (2009) 50, S9-14 www.lipidmaps.org

LIPID MAPS

TM

InformaticsInfrastructure

LipidData

Proteins

Pathways

Annotations

Genes

LIPIDOMICS COMPONENTS

Mass SpecLipid

StandardsLIPID MAPS

TM

www.lipidmaps.org

NIH U54 GM 69338

26

LIPID MAPS

TM

LIPID MAPS

TM

LIPID MAPSwww.lipidmaps.org

TM