Core labs and bridges

Core A: Administrative (Edward A. Dennis)

University of California San Diego
La Jolla, California

The Administrative Core is responsible for the overall scientific, fiscal, and administrative leadership of the LIPID MAPS Consortium including cores, bridges and Participating Investigators. It is also responsible for arranging and leading the meetings of the Advisory Committee, Steering Committee, and Operating Committee as well as meetings of Participating Investigators and other scientists working in this field.

Personnel:
Oswald Quehenberger, Scientific Coordinator, LIPID MAPS
Masada Disenhouse, Administrative Coordinator, LIPID MAPS

Consultants (Participating Investigators):
John Wooley, University of California, San Diego

Core B/C: Bioinformatics and Data Coordination (Shankar Subramaniam)

University of California San Diego
La Jolla, California

A comprehensive understanding of lipidomic networks is essential before models of cells in normal and pathological conditions can be developed. The primary objective of Core B is to coordinate the data and knowledge from LIPID MAPS project and disseminate it to the larger research community. Core B has established a complex multi-tier informatics and computational infrastructure, including databases, applications and interfaces to store, analyze and summarize data from measurements of lipids, genes and proteins in macrophages from animal models. A comprehensive, internationally-recognized lipid classification system has been established, lipid and gene/protein databases have been set up and a suite of bioinformatics tools related to lipid structure and lipid mass spectrometry have been developed. The major focus of Core C is Bioinformatics and Systems Biology of Lipidomic networks. The specific objectives include statistical analysis of data to decipher regulation of lipids under normal and pathological conditions, reconstruction of lipidomic networks, development of mechanisms and hypotheses of lipid modules involved in pathology and quantitative analysis of lipids in a context-specific manner. Core C has established an interactive infrastructure to store experimental “metadata”, process and analyze lipid MS data on macrophage studies from all the LIPID MAPS cores, and to integrate complementary gene array and proteomic data with the lipid studies. There are ongoing efforts to develop methods to analyze gene expression changes to decipher coordinately regulated genes and pathways and study of fluxes of lipids through the metabolic network. Modeling the influence of genetic and pharmacological perturbations forms another aspect of this project.

Personnel:
Core B/C
Eoin Fahy, University of California, San Diego, Project Coordinator
Robert Byrnes University of California, San Diego, Research Programmer
Dawn Cotter, University of California, San Diego, Senior Computational Scientist, Webmaster
Shakti Gupta, University of California, San Diego, Research Programmer
Mano Maurya, University of California, San Diego, Research Programmer
Manish Sud, University of California, San Diego, Cheminformatics Research Scientist

Consultants (Participating Investigators):
Henri Brunengraber, Case Western Reserve University

Core D: Macrophage Biology and Functional genomics (Christopher K. Glass)

University of California San Diego
La Jolla, California

The Macrophage Biology and Functional Genomics Core is structured as a component of the LIPID MAPS consortium to accomplish the following specific aims: 1. Develop standardized protocols for isolation, expansion and analysis of primary macrophages and macrophage cell lines. Central preparation of cells will enable LIPID MAPS lipidomics cores to characterize lipids under the most uniform conditions possible and allow results in one core unit to be directly compared to results in other core units. 2. Characterize expression patterns of genes involved in lipid sensing and metabolism and responses of macrophages to bioactive lipids. The Macrophage Biology and Functional Genomics Core Facility uses whole genome microarrays to profile the expression patterns of genes that encode proteins involved in the production, sensing, uptake, catabolism and cellular efflux of specific lipid metabolites in macrophages under basal and stimulated conditions. The results of these studies are correlated with studies carried out in lipid analysis core facilities, allowing regulatory, biosynthetic and degradation/export pathways to be defined. Gene expression data generated by these studies is posted in the Experimental Data section of the LIPID MAPS website. 3. The Macrophage Biology and Functional Genomics Core validates RNA interference reagents and uses macrophages derived from knockout mice to investigation potential roles of genes involved in lipid sensing and metabolism.

Personnel:
Donna Reichart, Core Coordinator
Gary Hardiman, Director, UCSD BIOGEM Microarray Core Facility

Consultants (Participating Investigators):
Peter Henson, National Jewish Medical/Research Center

Core E: Glycerolipids (Robert C. Murphy)

University of Colorado Denver
Aurora, Colorado

The investigations proposed in Core E involve the application of state-of-the-art mass spectrometry to be applied to the quantitative and qualitative analysis of neutral lipids present in cells in culture and tissues as part of coordinated studies of LIPID MAPS. General methods for the isolation and class separation of neutral lipids present in the biological samples have been developed using normal phase chromatography as the critical step in separating neutral lipid classes. Internal standards will be used to enable the quantitative analysis of triacylglycerols, monoalkylether diacylglycerols, and diacylglycerols at the isobaric molecular species level and molecular species analysis of the cholesterol esters. The strategy to accurately determine diacylglycerol molecular species in these samples involves derivatization to reduce acyl group migration during chromatographic separations, making them more amenable to normal phase LC/MS quantitation.

Lipids Analyzed:
Lipid category (and other classes): Glycerolipids (cholesteryl esters)
Examples of species analyzed: MAG, DAG, TAG, CE

Personnel:
Robert Barkley, Instructor
Deborah Beckworth, Administrative Assistant
Thomas Leiker, Research Associate

Consultants (Participating Investigators):
Dennis Voelker, University of Colorado Denver

Core F: Lipid Synthesis (Walter A. Shaw)

Core F(A): Lipid Standards (Walter A. Shaw)


Avanti Polar Lipids
Alabaster, Alabama

Core F(B): Synthesis Design (Michael S. VanNieuwenhze)
Indiana University
Bloomington, Indiana

The Lipid Synthesis and Biophysical Characterization Core (Core F) will serve the LIPID MAPS Consortium by providing all aspects of synthetic chemistry support for each of the Lipidomics Cores as well as biophysical characterization support for all lipids of interest to the consortium. The Lipid Standards and Production Chemistry Unit, represented by Avanti Polar Lipids, Inc. will provide lipid standards to be used by investigators participating in the consortium. Avanti will synthesize a library of lipids for use as analytical standards as well as provide materials for biological assays. Novel lipids provided to the consortium by Avanti will be made available to the general scientific community for the benefit of lipidomic research. The Novel Lipid Synthetic Design Unit will provide synthetic chemistry support for all new lipids and lipid intermediates discovered by the consortium. The Unit will work close with Avanti Polar Lipids, Inc. for the transfer of technology to enable production-scale synthesis of novel lipids discovered by the consortium. This unit will also work closely with the Structural Lipidomics and Other Lipids Core (Core K) to provide chemistry support to assist structure elucidation efforts. The Biophysical Characterization Unit will use well-established methods, including calorimetry and x-ray diffraction, to study the biophysical properties of novel lipids discovered by the Lipidomics Cores. This group will also study the interaction of lipopolysaccharide (LPS) with biological membranes and model macrophage membranes in support of the LIPID MAPS Consortium.

Personnel:
Core F(A)
Jeff D. Moore, Avanti Polar Lipids, Inc., Director Analytical Technologies
Renee S. Underwood, Avanti Polar Lipids, Inc., Administrative Contact

Core F(B)
William Turner, Indiana University, Research Scientist

Consultants (Participating Investigators):
Core F(A)
Camille Falck, UT Southwestern Medical Center
Kirk Maxey, Cayman Chemical

Core F(B)
Dale Boger, Scripps Research Institute

Core G: Fatty Acyls (Edward A. Dennis)

University of California San Diego
La Jolla, California

As part of the Consortium's discovery approach to lipidomics, Core G (the Fatty Acyl Core) has assumed the task of identifying all free fatty acids and fatty acid metabolites (FAMs) present in and secreted by macrophages and to quantitate the levels of all FAMs in these cells in the resting state and after various stimulations. FAMs include, but are not restricted to, the prostanoids, hydroxyl- and hydroperoxy-eicosaenoic acids, leukotrienes, epoxyeicosatrienoic acids, free fatty acids, and fatty acid amides. Resting macrophages contain and secrete very low levels of FAMs. These compounds are usually generated in response to a signal, are produced for a specific function, and are often potent second messengers. During the first phase of the project, Core G has completed the development of all methodologies for the analysis of FAMs in cells as well as extracellular fluids. All procedures have been validated and a time resolved comprehensive profile of FAMs has now been established for the first time for a macrophage cell line as well as for primary macrophages in the resting state and responding to inflammatory stimuli. The data have been posted on this website and are available to the public. Similar studies are currently being carried out for bone marrow derived promyelocytic cells. The initial step in the pathways leading to FAM generation is the liberation of the fatty acid from lipids involving phospholipase A2. The fatty acids thus released can enter myriad metabolic pathways resulting in hundreds of FAMs, many of which are highly bioactive. The number of pathways involved, coupled with the fact that FAMs have such similar chemical structures and either similar or opposing pharmacological reactivities, suggests that there is a complex flow of FAMs through these metabolic networks. In collaboration with Bridge A (LIPID MAPS Networks Bridge), Core G has developed techniques for detecting such networks. Results from initial studies demonstrate that “lipid networks” are indeed operative in this class of lipid mediators and their identification will be a major effort in the coming years.

Lipids Analyzed:
Lipid category (and other classes): Fatty Acyls
Examples of species analyzed: Free fatty acids, fatty acid amides, prostanoids, hydroxyl- and hydroperoxy-eicosanoic acids, epoxyeicosatrienoic acids, leukotrienes

Personnel:
Oswald Quehenberger, Scientific Coordinator, LIPID MAPS
Aaron Armando, SRA
Joshua Brooks, Post Doc
Matthew Buczynski, Post Doc

Consultants (Participating Investigators):

Jack Roberts, Vanderbilt University Medical Center
Charles Serhan, Harvard Medical School

Core H: Glycerophospholipids (H. Alex Brown)

Vanderbilt University
Nashville, Tennessee

The primary goal of the Glycerophospholipid Core H of the LIPID MAPS Project has been to develop a state of the art approach to qualitative and quantitative analysis of phospholipids. The goal of resolving, identifying, quantitating, and analyzing over 1000 distinct species of phospholipids in the macrophage is formidable. Lipidomics is a branch of metabolomics, and as such there are opportunities to learn much about cellular processes and the course of pathological states by monitoring lipid profiles. We have successfully achieved absolute quantitative analysis of a broad spectrum of cellular phospholipids, supported by an array of odd-carbon internal standards. One of the primary areas of focus of the consortium has been determining the cascade of membrane signaling events that occurs in response to lipopolysaccaride (LPS) or Kdo2-Lipid A stimulation of the macrophage. This includes a coordinated analysis using lipid metabolism oriented gene arrays by the Cell Biology Core. These studies will likely focus on a number of phospholipases, lipid kinases, and lipid phosphatase enzymes, as well as other targets. We have identified the major classes and species of phospholipids involved in LPS signaling, as well as other cell surface receptor pathways. This will establish metabolic interconnections between classes of lipids (e.g., precursor-product relationships between phospholipids and glycolipids), which will help identify bioactive species and direct future studies of molecular processes in the macrophage. We have also identified several atypical lipid species and illuminated new functions for known phospholipids species. Our work has led to ongoing collaborations within the consortium (e.g., parallel measurements of eicosanoids and lyso-phospholipids), as well as several external projects. We are pleased to have two distinguished Participating Investigators, Dr. Lewis Cantley at Harvard Medical School and Dr. Larry Marnett at Vanderbilt Medical Center. More information about related projects can be found at http://www.alexbrownlab.org.

Lipids Analyzed:
Lipid category (and other classes): Glycerophospholipids
Examples of species analyzed: PC, PE, PG, PS, PI (and polyphosphate derivatives), PA, lysophospholipids, plasmalogens and other ether-linked phospholipids, prostanoid containing phospholipids

Personnel:
Steve Milne, Lead Scientist
David Myers, Biostatistician

Consultants (Participating Investigators):
Lewis Cantley, Harvard Medical School
Lawrence Marnett, Vanderbilt University School of Medicine

Core I: Sphingolipids (Alfred H. Merrill, Jr.)

Georgia Institute of Technology
Atlanta, Georgia

This LIPID MAPS Core develops methods to analyze sphingolipids (and glycosphingolipids) and evaluate their occurrence, metabolism, regulation and interactions with other lipid signaling pathways in macrophages and other biological samples. Liquid chromatography-electrospray ionization mass spectrometric (LC ESI-MS/MS) methods already developed by this Core allow the quantitative analysis of all of the intermediates of de novo sphingolipid biosynthesis through sphingomyelins, ceramide phosphoethanolamines, glucosyl- and galactosyl-ceramides, lactosylceramides and sulfatides, as well as key signaling metabolites such as ceramide 1-phosphate and sphingosine 1-phosphate. In addition, it has identified a new category of mammalian sphingoid bases (1-deoxysphinganines, 1-desoxymethylsphinganines and the N-acyl-derivatives), and developed the first LC ESI-MS/MS method for quantitative analysis of a wide range of fatty acyl-CoA’s to facilitate studies of ceramide synthases as well as integrate sphingolipid metabolism with other lipid pathways. As the internal standards become available, Core I will develop quantitative methods for additional neutral and acidic glycosphingolipids by LC ESI- and MALDI- MS/MS, in combination with MSn to evaluate connectivity. These methods are highly sensitive (typically requiring only 10*6 cells) and will be used to determine how agonists (such as Kdo2-Lipid A, oxidized LDL and others) affect sphingolipid metabolism in macrophages, and to conduct studies with other biological samples, where appropriate. Core I will also utilize stable isotope precursors such as [13C]-palmitic acid to characterize changes in sphingolipid biosynthesis versus metabolic turnover. The data from these studies will be evaluated by novel data analysis and visualization tools developed at Georgia Tech and in collaboration with the LIPID MAPS Bioinformatics Core. These complementary tools will be widely useful for studies of sphingolipid composition, how metabolism is regulated, the role(s) of sphingolipids as modulators and mediators of cellular responses to stimuli, and how sphingolipid metabolism is connected to other lipid metabolic and signaling pathways.

Lipids Analyzed:
Lipid category (and other classes): Sphingolipids
Examples of species analyzed: Sphingomyelin, glycosphingolipids, ceramides, sphingosine phosphate, acyl CoAs

Personnel:
M. Cameron Sullards, Principal Research Scientist
Sarah Spiegel, Participating Investigator
Robert Yu, Participating Investigator
Elaine Wang, Research Scientist
Samuel Kelly, LIMS Coordinator
Chris Haynes, Graduate Student
Consultants (Participating Investigators):
Sarah Spiegel, Virginia Commonwealth University
Robert Yu, Medical College of Georgia

Core J: Sterol Lipids (David W. Russell)

UT Southwestern Medical Center
Dallas, Texas

Sterols play important structural, signaling, and regulatory roles in macrophage biology. Cholesterol, the most abundant sterol in mammalian cells, together with glycerophospholipids and sphingolipids, is required to maintain the integrity of the plasma membrane and to modulate fluidity and phase transitions in this essential barrier. Cholesterol and sphingolipids also form specialized plasma membrane rafts or caveolae, which concentrate tyrosine kinase receptors and other molecules that transmit signals into the cell. The regulatory roles of sterols in macrophages are illustrated by their abilities to serve as agonists for nuclear hormone receptors, as suppressors of cholesterol biosynthesis, and as products of cholesterol excretion and turnover. The diverse functions of sterols, together with their structural complexity, suggest that novel sterols and biological roles remain to be discovered. The goal of the Sterol Core is to identify and quantitate sterols in macrophages. Working in collaboration with the LC/MS Analysis Core, mass spectrometry procedures have been devised to extract, identify, and measure the major and minor sterols of resting and activated macrophages. These methods are applied to determine how the macrophage sterolome changes in response to lipopolysaccharide, cytokine and phagocytic challenges. A second objective of the Sterol Core is to identify the enzymes responsible for the synthesis of sterols in macrophages. Candidate cDNAs are identified based on the regulation of their encoding genes by stimuli that activate macrophages. Mass spectrometry and interference RNA approaches are used to identify a candidate enzyme's sterol substrates and products. A third goal of the Sterol Core is the identification of the lipid substrates of orphan cytochrome P450 enzymes found in macrophages and other cell types. The combined expertise of the LIPID-MAPS consortium is utilized together with expression of P450 cDNAs, mass spectrometry, and interference RNA to determine the substrates and products of this large class of enzymes known to be crucial for lipid synthesis and catabolism. Research carried out in the Sterol Core provides new insight into the roles of sterols and other lipids in the macrophage, a cell type relevant to immunity, inflammation, and atherosclerosis.

Lipids Analyzed:
Lipid category (and other classes): Sterol lipids
Examples of species analyzed: Isoprenoids, cholesterol, oxidized steroids, sterols, bile acids

Personnel:
Jeffrey McDonald, Project Coordinator
Bonne Thompson, Project Coordinator
Consultants (Participating Investigators):
Michael Brown, UT Southwestern Medical Center
Joseph Goldstein, UT Southwestern Medical Center

Core K: Prenols and Other Lipids (Christian R.H. Raetz*)

Duke University
Durham, North Carolina

One of the major aims of the Lipid Maps project, and of Core K in particular, is to discover novel lipids, with emphasis on those from mouse RAW264.7 macrophage tumor cells. There is ample biochemical and genomic evidence indicating the existence of novel lipids. For instance, radiochemical experiments with high levels of 32Pi indicate the presence of many unidentified minor phospholipids at 0.1 % or less of the total lipids of prokaryotic and eukaryotic cells. Genomic analyses likewise reveal the existence of many proteins of unknown function, some of which are undoubtedly involved in the biosynthesis of the minor unknown lipids. State-of-the-art, high-resolution mass spectrometry represents a powerful initial approach to the identification and structural characterization of novel lipids. Over the past grant period Core K has identified several novel lipids in animal cells, including N-acyl-PS and dolichoic acid. The impact of novel lipid structure elucidation cannot be understated, as illustrated by the elucidation of Kdo2-lipid A biosynthesis in E. coli. In the scheme of functional genomics, structure determination of novel lipids represents a critical first step that facilitates the subsequent hypothesis-driven elucidation of new enzymatic pathways responsible for the formation of the novel lipids from known compounds. Once enzymatic in vitro systems are in place, the techniques of expression cloning and protein purification in conjunction with sequencing quickly serve to identify the relevant structural genes encoding the new enzymes. The outcome is the definitive functional annotation of open reading frames of previously unknown functions. Core K is also developing new methods for the detection and quantification of various polyprenols, ubiquinones, and cardiolipins, which are involved in protein glycosylation, electron transport and mitochondrial assembly respectively, contributing to the emerging field of lipid systems biology. Several novel polyisoprenes have recently been recently identified.

Lipids Analyzed:
Lipid category (and other classes): Prenol and Other Lipids (cardiolipins, saccharolipids )
Examples of species analyzed: Polyisoprene-linked phosphate sugars, dolichols, quinones, , cardiolipins, saccharolipids, novel lipids

Personnel:
Ziqiang Guan, Duke University, Associate Research Professor
David Six, Duke University Medical Center, Research Associate
Teresa A. Garrett, Assistant Professor, Vassar College
Gregory Laird, SRA, Duke University
Consultants (Participating Investigators):
Dale Poulter, University of Utah
Richard Ulevitch, Scripps Research Institute

*Chris Raetz is deceased; the lab is now run by Ziqiang Guan

Bridge A: LIPID MAPS Networks (Shankar Subramaniam)

University of California San Diego
La Jolla, California

The main objective of this Bridge Project is the reconstruction and modeling of lipidomic networks in macrophages. In the first part of this objective, a combination of inference and statistical learning based methods will be used to reconstruct networks from lipid and gene expression data measured by the experimental core laboratories in the LIPID MAPS project. The statistical learning approach includes use of principal component reduction regression and temporal analysis of modules. The LIPID MAPS project also intends to carry out experiments with stable isotope metabolite precursors. These include C13 13C-labeled arachidonate, acetate, palmitate and mevalonate. The Bridge project is developing quantitative methods for the modeling and analysis of the isotopomeric data in order to provide kinetic analysis of the models. As a consequence, it will be possible to design novel experiments and develop quantitative hypotheses for pharmacological and genetic perturbations of the lipid networks. Unlike protein networks, little is known about lipid networks in the context in of mammalian cells. Development of such networks requires a systems biology approach with large scale measurements of defined systems followed by mathematically intensive integrative analysis of the data to develop network models. An extensive effort has been placed on the development of interactive software tools to create metabolic pathways and to map lipid, gene and protein data generated by the LIPID MAPS experimental cores on these pathways. These models serve as hypotheses for understanding cellular function in normal and pathological conditions. This bridge will lead to development of new methods for reconstruction and modeling of lipid networks and will provide the community with tools for pathway-based approaches to study cellular function.

Personnel:
Mano Ram Maurya, Asst. Project Scientist
Robert Byrnes, Research Programmer
Dawn Cotter, Senior Computational Scientist, Webmaster
Eoin Fahy, Project Coordinator
Shakti Gupta, Research Programmer
Xiang Li, Research Programmer
Manish Sud, Cheminformatics Research Scientist
Yihua Zhao, Research Programmer

Consultants (Participating Investigators):
Joanne Kelleher, Massachusetts Institute of Technology

Bridge B: Transcriptional Regulation in Macrophages (Christopher K. Glass)

University of California San Diego
La Jolla, California

The Transcriptional Regulation in Macrophages Bridge will combine molecular and cellular analysis with data generated by the LIPID MAPS Consortium to identify, characterize and model PPAR-dependent and LXR-dependent transcriptional networks that sense and regulate lipid metabolism in the macrophage.

Personnel:
Norihito Shibata, Post Doc
Nathan Spann, Post Doc
Consultants (Participating Investigators):
Jerry Olefsky, University of California, San Diego

Bridge C: Lipid Imaging (Robert C. Murphy)

Bridge C(A): Lipid Imaging (Robert C. Murphy)
University of Colorado Denver
Aurora, Colorado

Bridge C(B): Subcellular Imaging (Nicholas Winograd) Penn State University
University Park, PA

The studies proposed in Bridge C involve basic research into the develop of mass spectrometric techniques that can be used to generate images defining specific location and relative abundance of lipids within tissues and cells. In part, this research program builds on the success of using matrix assisted laser desorption ionization (MALDI) coupled to a quadrupole tandem time of flight mass spectrometer and application of the matrix onto thin tissue slices to enhance ion yields following irradiation of small areas of tissue with a focused laser beam. The resultant secondary ions emitted are then mass analyzed and stored as mass and intensity values at the x, y coordinates of the laser spot. The laser beam is then rastered to the next adjacent area to generate additional mass spectral data eventually building a large database that can be used to generate detailed images of tissues based upon the abundance of specific lipid molecular species. Secondary ion mass spectrometry (SIMs) using Buckminster fullerene (C60+) ion beams will be systematically studied to bring lateral resolution of lipid imaging below 10 μm so that lipid distribution close to the cellular regime can be realized. Specific goals include development of derivatization chemistry to enhance lipid secondary ion yield in both MALDI and SIMS imaging experiments in order to discover novel lipids. New tissue embedding materials will be developed and explored that will be specifically suited for mass spectrometric imaging. The reproducibility of lipid anatomical images will be assessed by analysis of sequential tissue slices as well as analysis identical tissue regions from different animals. The results from the MALDI mass spectrometric images will be compared to microdissection and analysis of lipid abundances by electrospray LC/MS/MS techniques in order to establish the validity of the MALDI imaging ion intensities that reveal concentrations of lipids in their differential tissue distribution. This research will develop novel and powerful research methods that can be used to examine tissues (biopsies) taken from human subjects to define molecules that mark unique disease processes such as atherosclerosis and possibility diabetes.

Personnel:
Bridge C(A)
Robert Barkley, Instructor
Deborah Beckworth, Administrative Assistant
Joseph Hankin, Instructor

Consultants (Participating Investigators):
Catherine Costello, Boston University School of Medicine

Bridge D: Oxidized Lipids in Macrophages (Joseph L. Witztum)

University of California San Diego
La Jolla, California

Oxidized LDL (OxLDL) is believed to play a major role in atherogenesis due to its major proinflammatory and proatherogenic properties. There is strong evidence many of these effects are mediated by the variety of oxidized lipid components generated when LDL undergoes oxidation. Studies of the biological properties of oxidized LDL have mostly utilized LDL oxidized in vitro, typically by exposure to copper, producing a profoundly or “maximally” oxidized LDL (OxLDL), however this situation may not occur in vivo. An earlier form of LDL (mildly oxidized form) termed minimally oxidized LDL (mmLDL) more closely relates to what actually occurs in vivo and has a higher relevance to lipid oxidation moieties observed in atherosclerotic lesions. Yet little is known about the bioactive oxidized lipid moieties contained in mmLDL. Employing a variety of high performance liquid chromatography coupled to mass spectrometry techniques (HPLC-MS), we are currently analyzing the oxidized cholesteryl ester and phospholipids components contained in mmLDL to determine their bioactivities and structural features. Knowledge of the actual oxidized lipid moieties generated when LDL undergoes cell-mediated oxidation can provide novel insight into the mechanisms of proinflammatory response and atherogenesis.

Personnel:
Yury Miller, Associate Professor
Karsten Hartvigsen, Investigator