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This meeting took place in 2005



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PPAR/LXR (Z2)


Organizer(s) Christopher Glass and Mitchell A. Lazar
April 12—17, 2005
Fairmont Chateau Whistler • Whistler, British Columbia Canada
Abstract Deadline: Dec 13, 2004
Late Abstract Deadline:
Scholarship Deadline:
Early Registration Deadline: Feb 14, 2005

Part of the Translational Medicine Series, Supported by Pfizer Global Research and Development


Summary of Meeting:
The accelerating incidence of obesity, insulin resistance and hyperlipidemia in Westernized societies and the attendant complications of diabetes and atherosclerosis is fueling an explosion of interest in the molecular mechanisms underlying metabolic disease. The PPAR subfamily of nuclear receptors, consisting of PPARa, PPARg, and PPARd, initially became the focus of intense investigation following discoveries of roles of PPARa and PPARg in controlling aspects of lipid and glucose homeostasis. PPARs regulate programs of gene expression by functioning as ligand-dependent transcription factors. Although the range of physiological ligands that regulate the activities of each PPAR in vivo remain to be clearly defined, PPARa and PPARg are the molecular targets of fibrates and thiazolidinediones that were identified empirically to lower circulating triglyceride levels and to improve insulin resistance in diabetic patients, respectively. The recognition that these classes of drugs exert their therapeutic effects by binding to PPARa and PPARg suggests that more effective drugs for the treatment of hyperlipidemia and type 2 diabetes can be developed by optimizing ligand-receptor interactions. Furthermore, recent studies have suggested additional roles of PPARs in a diverse range of physiological and pathophysiological settings, including vascular wall biology, placental physiology, atherosclerosis, inflammatory bowel and skin disorders, metabolic bone disease and cancer. Further exploration of these observations should expand our general understanding of important developmental and homeostatic processes at a molecular level, and may lead to new avenues of therapeutic intervention in common human diseases. Because of the potential biomedical significance of this field of research, studies of PPAR-related processes have resulted in a number of pioneering discoveries of general importance to molecular biology and development. In concert with recent developments in the PPAR field, a parallel of series of discoveries has emerged relating to regulation of cholesterol and triglyceride homeostasis by the LXR subfamily of nuclear receptors, consisting of LXRa and LXRb. The LXRs are activated by cholesterol metabolites and provide the basis for a feed-forward homeostatic control circuit for maintenance of cellular cholesterol levels. The biological actions of LXRs relate in part to their ability to regulate members of the ABC family of lipid transporters, including ABC A1 and ABC G1, which mediate the efflux of cholesterol from cells. These findings raise the possibility that new classes of cholesterol lowering drugs could be developed that would work synergistically with currently available agents. These considerations justify a Keystone Conference focused on PPARs and LXRs in 2005. The PPAR field is entering a new wave of discovery based on the recent success in generating conditional experimental systems for analysis of PPARg and PPARd-null mice. Studies for metabolic pathways regulated for PPARs and LXRs are also benefiting from the application of increasingly powerful genomics and proteomics tools. A 2005 Keystone Meeting on PPARs and LXRs will be well timed to bring together a diverse array of investigators from academia and industry to synthesize the most recent developments and define future directions. This meeting will also provide opportunities to highlight major findings from studies of less well-characterized members of the nuclear receptor family that have recently emerged as potential regulators of lipid metabolism and energy homeostasis, such as FXR. Finally, this meeting will continue to be a valuable opportunity for trainees to present work in a poster session, meet leaders in the field, and explore opportunities for future career development.

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Conference Program    Print  |   View meeting in 12 hr (am/pm) time


TUESDAY, APRIL 12

15:00—19:30
Registration

Macdonald Foyer
18:30—19:30
Refreshments

Macdonald Foyer
19:30—20:30
Keynote Address (Joint)
Meeting has ended...abstracts no longer viewable online.

MacDonald ABC
* Garret A. FitzGerald, University of Pennsylvania, USA

* Christopher K. Glass, University of California, San Diego, USA

Cynthia Kenyon, Calico, USA
Aging and Metabolism: Lessons from C. elegans


WEDNESDAY, APRIL 13

07:00—08:00
Breakfast

MacDonald DEF
08:00—11:15
Lipid Ligands and Nuclear Receptors (Joint)
Meeting has ended...abstracts no longer viewable online.

MacDonald ABC
* Mitchell A. Lazar, Perelman School of Medicine, University of Pennsylvania, USA

Ronald M. Evans, Howard Hughes Medical Institute, Salk Institute, USA
PPARs at the Nexus of Inflammation and Metabolism

David J. Mangelsdorf, University of Texas Southwestern Medical Center, USA
The Contrasting Roles of LXRs and FXR in Lipid Metabolism

H. Alex Brown, Vanderbilt University, USA
Lipids and Signaling Networks

Beverly Koller, University of North Carolina at Chapel Hill, USA
Eiscosanoids and Related Products in Inflammation

Barry Marc Forman, City of Hope, USA
Short Talk: Identifying True Endogenous Ligands for Lipid Receptors

Naoka Murakami, Brigham and Women's Hospital, USA
Short Talk: G2A is a Proton-Sensing G-Protein Coupled Receptor, Antagonized by Lysophosphatidylcholine

09:20—09:40
Coffee Break

Macdonald Foyer
11:15—13:00
Poster Setup

Macdonald DEF
13:00—22:00
Poster Viewing

Macdonald DEF
15:00—16:30
Workshop 1: Hot Topics/Lipid Receptors

MacDonald BC
* Richard A. Heyman, ORIC Pharmaceuticals, USA

* Barry Marc Forman, City of Hope, USA

Thomas P. Burris, St. Louis University School of Medicine, USA
Regulation of Carbohydrate Metabolism by the Farnesoid X Receptor

Jason M. Held, Washington University in St. Louis, USA
Progress on Identifying the Endogenous Ligand of DAF-12, an Orphan Nuclear Receptor in C. elegans

Darja Debevec, Institute of Reproductive and Developmental Biology, UK
Repression of Nuclear Receptor Regulated Genes by RIP140 Controls Adipocyte Function

Seung-Whan Kim, University of Ulsan, College of Medicine, South Korea
Regulation of Insulin Secretion and beta-cell Mass by Activating Signal Cointegrator-2

Yejun Tan, Rosetta Inpharmatics LLC, USA
An Adipocyte Transcriptosome-Based PPARgamma Activation Index that Discriminates between Full Agonists and SPPARgammaMs

Aixue Liu, GlaxoSmithKline Pharmaceuticals, USA
Laser Capture Micro-Dissection (LCM) Based Gene Expression Analysis Reveals Decreased PGC-1 Expression in Slow Fibers of db/db Mice Skeletal Muscle

Toshiya Tanaka, University of Tokyo, Japan
Peroxisome Proliferator-Activated Receptor delta (PPARdelta) Agonist Improves Adipocytokine Production and Prevents High Fat Diet Induced Obesity and Insulin Resistance with Long-Term Efficacy

Knut R. Steffensen, Karolinska Institute, Sweden
Genome Wide Expression Profiling; A Panel of Mouse Tissues Discloses Novel Biological Functions of LXRs In Adrenals

15:00—16:45
Workshop 1: Hot Topics/Lipids

MacDonald A
* Ian A. Blair, University of Pennsylvania, USA
Lipidomics and Proteomics in Cancer

William L. Smith, University of Michigan, USA
PGH Synthases: Peroxidase Substrate Specificity and Eicosapentaenoic Acid Oxygenation

Timothy T. Hla, Boston Children's Hospital/Harvard Medical School, USA
Sphingosine 1-Phosphate Signaling: to the Vascular System and Beyond

Christer S. Ejsing, MPI of Molecular Cell Biology and Genetics, Germany
Short Talk: Shotgun Lipidomics - Unleashing the Power of Mass Spectrometric Lipid Analysis

16:30—17:00
Coffee & Snacks Available

Macdonald Foyer
17:00—19:00
Molecular Mechanisms
Meeting has ended...abstracts no longer viewable online.

MacDonald BC
Myles Brown, Dana-Farber Cancer Institute, USA
Chromosome-Scale Analysis of Nuclear Receptor Action

* Janardan K. Reddy, Northwestern University Medical School, USA
Nuclear Receptor Coactivators in PPAR Action

Timothy M. Willson, GlaxoSmithKline, USA
Characterization of PPARgamma Modulators Derived from Structure-Guided Synthesis

Pere Puigserver, Dana-Farber Cancer Institute, Harvard Medical School, USA
Short Talk: Nutrient Control of Glucose Metabolism Through PGC-1alpha/SIRT1 Complex

17:00—19:30
Lipids and their Enzymes
Meeting has ended...abstracts no longer viewable online.

MacDonald A
* Michal Laniado-Schwarztman, New York Medical College, USA
Cytochrome P450 Products of Arachidonic Acid in Renal and Cardiovascular Function

Steven A. Farber, Carnegie Institution of Washington, USA
Visualizing Lipid Metabolism and Germ Cell Migration in Live Zebrafish:A Genetic Screen With Guts

Colin D. Funk, Queen's University, Canada
Novel Mouse Models for Elucidating Eicosanoid Functions

Roy J. Soberman, Harvard Medical School, USA
The Membrane Organization of Leukotriene Synthesis

H. Eric Xu, Van Andel Research Institute, USA
Short Talk: Structural and Functional Identification of Phospholipids as Ligands for the Orphan Nuclear Receptor Steroidogenic Factor-1

19:00—20:00
Social Hour

Macdonald Foyer
19:30—22:00
Poster Session 1

Macdonald DEF

THURSDAY, APRIL 14

07:00—08:00
Breakfast

MacDonald DEF
08:00—11:00
Metabolic Disease (Joint)
Meeting has ended...abstracts no longer viewable online.

MacDonald ABC
* Timothy T. Hla, Boston Children's Hospital/Harvard Medical School, USA

* Bruce M. Spiegelman, Harvard Medical School, USA

Takashi Kadowaki, University of Tokyo, Japan
Adiponectin and PPARs in the Metabolic Syndrome

Bruce M. Spiegelman, Harvard Medical School, USA
The PGC-1 Coactivators and the Control of Lipid Metabolism

Mitchell A. Lazar, Perelman School of Medicine, University of Pennsylvania, USA
Selective Modulation of PPAR and LXR By Nuclear Receptor Corepressors

Richard A. Heyman, ORIC Pharmaceuticals, USA
Short Talk: LXR and FXR; Drug Targets for Metabolic Syndrome

Gerhard Liebisch, University of Regensburg, Germany
Short Talk: Analysis of the Cellular Lipid Metabolism upon Cholesterol Loading using a Combination of Lipid Metabolic Profiling by ESI-MS/MS and mRNA Expression Analysis

09:20—09:40
Coffee Break

Macdonald Foyer
11:00—13:00
Poster Setup

Macdonald DEF
13:00—22:00
Poster Viewing

Macdonald DEF
15:00—16:30
Workshop 2: Hot Topics

MacDonald BC
* Hilde Irene Nebb, University of Oslo, Norway

* Jorge Plutzky, Brigham and Women's Hospital, USA

Grant D. Barish, The Salk Institute, USA
A Nuclear Receptor Atlas: Macrophage Activation

Michelle N. Bradley, University of California, Los Angeles, USA
LXR-Dependent Gene Expression is Important for Macrophage Survival and the Innate Immune Response

Brian N. Finck, Washington University School of Medicine, USA
Lipin 1 Is A Fasting-Induced PGC-1a Target Gene Upstream of PPARa

Michael Lehrke, Klinikum Grosshadern, Germany
Diet-Dependent Cardiovascular Lipid Metabolism Controlled by Hepatic LXRá

Ji Miao, , USA
The Xenobiotic Nuclear Receptors CAR and PXR Inhibit HNF-4 Signaling in Cholesterol and Glucose Metabolism

Ronni Nielsen, University of Southern Denmark, Denmark
Molecular Mechanisms of PPAR Subtype Specific Activation of Chromatin-Embedded Target Genes

David Alexander Sarruf, Novo Nordisk, Denmark
Cyclin D3 Promotes Adipogenesis through PPARg Activation

Attila Szanto, Massachusetts General Hospital, USA
Role of PPAR-gamma in Differently Activated Macrophages

15:00—16:45
Workshop 2: Hot Topics/Lipids

MacDonald A
* Robert F. Klein, Oregon Health & Science University, USA
Lipoxygenase and Skelatal Health

Robert C. Murphy, University of Colorado Denver, USA
Mass Spectrometry of Lipids: Qualitative and Quantitative Approaches for RAW Cells

Claudio Sturino, Merck Frosst Centre for Therapeutic Research, Canada
BP Program

Anne-Maria Curtis, University of Pennsylvania, USA
Short Talk: Blood Pressure and the Molecular Clock

16:30—17:00
Coffee & Snacks Available

Macdonald Foyer
17:00—19:00
Adipogenesis/Energy Homeostasis
Meeting has ended...abstracts no longer viewable online.

MacDonald BC
* Stephen R. Farmer, Boston University School of Medicine, USA
Molecular Mechanisms Regulating Adipogenesis: Interplay between PPARgamma and C/EBPalpha

Frank J. Gonzalez, National Institutes of Health, USA
Mice Humanized for PPARalpha are Resistant to the Hepatocarcinogenic Effects of Peroxisome Proliferators

David E. Moller, Eli Lilly and Company, USA
Novel PPARgamma Ligands and Mechanisms of Insulin Sensitization

Hilde Irene Nebb, University of Oslo, Norway
Short Talk: LXR in Metabolic Control

17:00—19:00
Lipidomics and Proteomics
Meeting has ended...abstracts no longer viewable online.

MacDonald A
* Edward A. Dennis, University of California, San Diego, USA
The Lipid Maps Consortium

Xianlin Han, Sanford Burnham Medical Research Institute, USA
Shotgun Lipidomics Based on Intrasource Separation and Multidimensional Mass Spectrometry: Principles and Applications

Hee-Yong Kim, National Institutes of Health, USA
Membrane Modification Characterized by Liquid Chromatography/Mass Spectrometry: Implication in Cell Signaling

Lawrence M. Sayre, Case Western Reserve University, USA
Protein Side-Chain Modification by Aldehyde Products of Lipid Oxidation

Kim Ekroos, University of Southern Denmark, Denmark
Short Talk: Unravelling Phospholipidomes by Shotgun Lipidomics

19:00—20:00
Social Hour

Macdonald Foyer
19:30—22:00
Poster Session 2

Macdonald DEF

FRIDAY, APRIL 15

07:00—08:00
Breakfast

MacDonald DEF
08:00—11:15
Inflammation (Joint)
Meeting has ended...abstracts no longer viewable online.

MacDonald ABC
* Carlo Patrono, University of Rome, Italy

Beatrice Desvergne, University of Lausanne, Switzerland
PPARs: Beyond the Cardiovascular Therapeutic Applications

Peter Tontonoz, University of California, Los Angeles, USA
Nuclear Receptors at the Crossroads of Lipid Metabolism and Inflammation in Macrophages

* Christopher K. Glass, University of California, San Diego, USA
Regulation of Macrophage Foam Cell Formation and Inflammatory Gene Expression by PPARs

Garret A. FitzGerald, University of Pennsylvania, USA
The Collapse of the Coxibs; Challenges and Opportunities in the Arachidonic Acid Cascade

Laszlo Nagy, Sanford-Burnham Medical Research Institute at Lake Nona, USA
Short Talk: PPARg in Antigen Presenting Cells Regulates Lipid Metabolism and Inflammatory Response

Ajay Chawla, University of California, San Francisco, USA
Short Talk: PPAR Functions in Macrophage Biology

09:20—09:40
Coffee Break

Macdonald Foyer
11:15—13:00
Poster Setup

Macdonald DEF
13:00—22:00
Poster Viewing

Macdonald DEF
16:30—17:00
Coffee & Snacks Available

Macdonald Foyer
17:00—19:00
Diabetes
Meeting has ended...abstracts no longer viewable online.

MacDonald BC
Willa A. Hsueh, Methodist Hospital Research Institute, USA
Cardiomyocyte Specific Deletion of PPARƒ× - Model of Diabetic Cardiomyopathy ?

V. Krishna K. Chatterjee, University of Cambridge, UK
Molecular Spectrum of Mutations in Human PPARg Associated with Severe Insulin Resistance

Yu-Hua Tseng, Joslin Diabetes Center/Harvard Medical School, USA
Transcriptional Control of Adipogenesis - Novel Insights from Gene Expression Profile

Barbara C. Hansen, University of South Florida, Tampa, USA
Short Talk: Insulin Sensitizing By A PPARalpha Specific Agonist K-111 Closely Relates To Reduced Subcutaneous Adipose Tissue Lipoprotein Lipase Activity In Obese Monkeys

17:00—19:30
Bioactive Lipids and Human Disease
Meeting has ended...abstracts no longer viewable online.

MacDonald A
Carlo Patrono, University of Rome, Italy
Aspirin-Resistant Eicosanoid Formation in Atherothrombosis

Jilly F. Evans, PharmAkea Therapeutics, USA
Leukotrienes and Cardiovascular Diseases

Joseph L. Witztum, University of California, San Diego, USA
Innate Immune Receptors Recognize Conformational Epitopes of Lipids

* Stanley L. Hazen, Cleveland Clinical Foundation, USA
Photo-Oxidation of Retinal Rod Outer Segment Phospholipids Serves as a Physiological “Eat Me” Signal for CD36-Mediated Phagocytosis by Retinal Pigment Epithelium

Gail E. Grant, Health Canada, Canada
Short Talk: Oxidative Stress Induces the Production of 5-oxo-ETE from Arachidonic Acid in B Cell Lines

19:00—20:00
Social Hour

Macdonald Foyer
19:30—22:00
Poster Session 3

Macdonald DEF

SATURDAY, APRIL 16

07:00—08:00
Breakfast

MacDonald DEF
08:00—11:00
New Frontiers (Joint)
Meeting has ended...abstracts no longer viewable online.

MacDonald ABC
* Ronald M. Evans, Howard Hughes Medical Institute, Salk Institute, USA

* Garret A. FitzGerald, University of Pennsylvania, USA

Daniel J. Rader, University of Pennsylvania, USA
Molecular Regulation of Reverse Cholesterol Transport

David A. Jones, University of Utah, USA
APC Control of Retinoic Acid and Prostaglandin Biosynthetic Enzymes

Ueli Schibler, University of Geneva, Switzerland
The Daily Rhythms of Genes Cells and Organs

Bing Ren, Ludwig Institute for Cancer Research, USA
Mapping the Genome's Second Code

Qianfei Jeffrey Wang, Lawrence Berkeley National Laboratory, USA
Short Talk: Primate Sequence Comparisons Identify Lineage Specific Regulatory Elements in Human Lipid Genes

09:20—09:40
Coffee Break

Macdonald Foyer
16:30—17:00
Coffee & Snacks Available

Macdonald Foyer
17:00—19:00
Cardiovascular Disease
Meeting has ended...abstracts no longer viewable online.

MacDonald BC
* Helen H. Hobbs, University of Texas Southwestern Medical Center, USA
Metabolic Effects of Non-Cholesterol Sterols

Daniel P. Kelly, University of Pennsylvania, USA
PPAR Signaling in the Normal and Diseased Heart

Bart Staels, Institut Pasteur de Lille, Université Lille, France
PPARa, the Metabolic Syndrome and Atherosclerosis.

Jorge Plutzky, Brigham and Women's Hospital, USA
Short Talk: Endogenous Mechanisms for Regulating PPAR Responses in Vascular Biology and Inflammation

17:00—19:00
Bioactive Lipid Signals
Meeting has ended...abstracts no longer viewable online.

MacDonald A
* Robert C. Murphy, University of Colorado Denver, USA

Yusuf A. Hannun, Stony Brook Cancer Center, USA
Neutral sphingomyelinases in eukaryotic cell regulation

Frank A. Fitzpatrick, University of Utah, USA
Inflammation and Lipid Mediators: Novel Mechanisms of Cancer Risk

Pallavi R. Devchand, Harvard Medical School, USA
Short Talk: Defining Impact of Lipid Signaling Circuits in the Colon After Resolution of Colitis

19:00—20:00
Social Hour

Frontenac ABC
20:00—23:00
Entertainment

Frontenac ABC

SUNDAY, APRIL 17

 
Departure


*Session Chair †Invited, not yet responded.



We gratefully acknowledge the generous grant for this conference provided by:


National Institutes of Health

Grant No. 1R13-DK070428-01




We gratefully acknowledge additional support for this conference from:

Pfizer Global Research & Development

We gratefully acknowledge additional in-kind support for this conference from those foregoing speaker expense reimbursements:



Exelixis, Inc.


GlaxoSmithKline


Merck Research Laboratories


Merck Research Laboratories


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