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Drug Metabolism
Gordon Research Conference

Celebrating the Future of Drug Metabolism

Dates

July 8-13, 2012

Location

Holderness School
Holderness, NH

Organizers

Chair:
Erin Schuetz

Vice Chair:
James B. Mangold

Meeting Description

2012 is the 42nd Drug Metabolism Gordon Conference and will focus on cutting-edge ADME research. The scientific program being developed will include topics such as Predicting drug metabolism using P450 structural information. Other topics include the importance of Environmental factors, such as seasonal variation and our gut genome, on drug metabolism. Time dependent inhibition of drug metabolism will also be covered. New tools for ADME studies such as stem cell derived tissue-specific cells and various Humanized mouse models will also be discussed. Other topic areas include metabolomics linking transporters and drug metabolizing enzymes to new metabolic pathways. A final focus will be new frontiers, new techniques, methodologies, and data analysis. The program will continue to follow the traditional GRC Drug Metabolism format with a Keynote lecture Sunday evening, four morning sessions - each with four speakers, and three evening sessions with three speakers each. The Wednesday evening program will feature a mix of six graduate students and post-doctoral fellows who will deliver oral presentations that are selected from the many outstanding posters submitted. Vice Chair James Mangold will organize the poster sessions and attendees are encouraged to submit posters. As always, this meeting offers a wonderful opportunity to learn and discuss unpublished research, discuss new ideas, and establish collaborations with senior and junior scientists from academia and industry. Of course we will maintain the traditions passed down from generations of Drug Metabolism Gordon Conferences including the historic Tuesday afternoon Academia vs. Industry softball game (bring those gloves!), Monday afternoon tennis and Wednesday afternoon golfing, and there are always hiking and canoeing outings in the beautiful White Mountains of New Hampshire. As always housing and all meals are included in the registration fee.

Contributors

Meeting Program

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmCelebrating the Future of Drug Metabolism
7:40 pm - 7:50 pmDiscussion Leader: Erin Schuetz (St. Jude Children's Research Hospital)
"Celebrating the Future of Drug Metabolism"
7:50 pm - 9:00 pmKeynote Speaker: Stephen G. Sligar (U. Illinois Urbana, Champaign)
"Drug Metabolism: The Good, The Bad and The Ugly"`
9:00 pm - 9:30 pmDiscussion
MONDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmMetabolomics Meets ADME
Discussion Leader: Frank Gonzalez (National Institutes of Health)
9:00 am - 9:30 amFrank Gonzalez (National Institutes of Health)
"Toxicity biomarkers and mechanisms revealed by non-targeted metabolomics"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amSanjay K. Nigam (U. California San Diego)
"SLC22 Drug Transporters in Remote Communication Mediated by Metabolites"
10:15 am - 10:30 amDiscussion
10:30 amCoffee Break
11:00 am - 11:30 amXiaochao Ma (U. Kansas Medical Center)
"Metabolomic Analysis Reveals Novel Mechanisms of the Drug Toxicity"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmSabrina M. Ronen (U. California San Francisco)
"Magnetic Resonance Detectable Biomarkers of Antineoplastic Treatment"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmPredicting Metabolism using Cytochrome P450 Structure
Discussion Leader: Steven A. Wrighton (Advion Biosciences)
7:30 pm - 8:00 pmEric F. Johnson (Scripps Research Institute)
"Crystalline P450 2D6: An Experimental Platform for Characterization of Substrate and Inhibitor Binding"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmEmily E. Scott (U. Kansas)
"Human Cytochrome P450 Active Site Adaptations to Ligand Structure - Within and Between Enzymes"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmJames R. Halpert (U. California, San Diego)
"Conformational Plasticity of Mammalian Cytochromes P450 2B: Implications for Prediction of Drug Metabolism from X-ray Crystal Structures"
9:20 pm - 9:30 pmDiscussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmEnvironmental and Dietary Factors Affecting Drug Metabolism and Response
Discussion Leader: Kenneth Thummel (U. Washington)
9:00 am - 9:30 amMary Paine (U. North Carolina)
"Predicting Interactions between Drugs and Dietary Substances by IVIVE"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amFrancis Levi (INSERM)
"Moderation of Xenobiotic Effects by Circadian Clocks"
10:15 am - 10:30 amDiscussion
10:30 amCoffee Break
11:00 am - 11:30 amErik Eliasson (Karolinska Institutet)
"Exploring the Potential Relationship between Individual Levels of Vitamin D and CYP3A-activity"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmAllan Rettie (U. Washington)
"Vitamin K Disposition: Generic and Environmental Factors- Implications for Drug Response"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmTime Dependent Inhibition
Discussion Leader: Andrew Parkinson (XPD Consulting)
7:30 pm - 8:00 pmAndrew Parkinson (XPD Consulting)
"The Impact of Experimental Design on the in vitro Assessment of Metabolism-Dependent Inhibition of CYP Enzymes"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmStephen D. Hall (Eli Lilly)
"Translation of Time-Dependent Inhibition Data into Clinical DDI Predictions"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmScott R. Obach (Pfizer)
"Challenges in the Prediction of CYP3A-based Drug-Drug Interactions from in vitro Time Dependent Inhibition: From Experimental rigor to Appropriate Modeling"
9:20 pm - 9:30 pmDiscussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmMice with Human Livers or Human ADME Genes for Drug Disposition Studies
Discussion Leader: Robert H. Tukey (U. California, San Diego)
9:00 am - 9:30 amC. Roland Wolf (U. Dundee)
"Application of Transgenic Animal Models to Predict Human Responses to Drugs and Chemical Toxins"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amAnshul Gupta (AstraZeneca)
"Humanized liver chimeric mouse-for assessing the impact of binding to human alpha-acid glycoprotein on metabolic clearance of compounds in a discovery program"
10:15 am - 10:30 amDiscussion
10:30 amCoffee Break
11:00 am - 11:30 amRobert Tukey (U. California, San Diego)
"Intestinal Glucuronidation in Humanized and Conditional Knockout Animal Models"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmJohn Bial (Yecuris)
"Chimeric Animal Models: Emerging Tools in Translational Medicine"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair
7:30 pm - 9:30 pmGraduate Student and Post-Doc Presentations
Discussion Leader: Henry Strobel (University of Texas, Houston Medical School)
7:30 pm - 7:45 pmJohn Thomas Barr (Washington State University)
"Impact of Probe Substrate Selection on Aldehyde Oxidase Inhibition Profiles: Implications for Mechanism and in Vitro DDI Prediction"
7:45 pm - 7:50 pmDiscussion
7:50 pm - 8:05 pmKlarissa Hardy (The University of Washington School of Pharmacy)
"Investigating Mechanisms of Lapatinib-induced Hepatotoxicity in Hepa RG Cells"
8:05 pm - 8:10 pmDiscussion
8:10 pm - 8:25 pmUpendra Dahal (Washington State University)
"Drug Metabolism by Cytochrome P450: Effects of Nitrogen - Iron Coordination on Affinity and Metabolic Stability"
8:25 pm - 8:30 pmDiscussion
8:30 pm - 8:45 pmDiana Schuster (The University of Washington)
"Gene Expression Profiling of Maternal Liver, Kidney and Small Intestine in Pregnant Mice"
8:45 pm - 8:50 pmDiscussion
8:50 pm - 9:05 pmJamie D'Agostino (The University of Michigan)
"Mechanism - based Inactivation of Human Cytochrome P450 2B6 by Chlorpyrifos and Related Organophosphate Pesticides"
9:05 pm - 9:10 pmDiscussion
9:10 pm - 9:25 pmYi Xiao (Vanderbilt School of Medicine)
"Cytochrome P450 2W1 Oxidizes both Lysophospholipids and Free Fatty Acids"
9:25 pm - 9:30 pmDiscussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmTransporters: "Back to the Future"
Discussion Leader: John D. Schuetz (St. Jude Children's Research Hospital)
9:00 am - 9:30 amRobert Jansen (Netherlands Cancer Institute)
"Transportomics: Screening for Substrates of ABC Transporters in Body Fluids using Vesicular Transport Assays"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amGerhard Ecker (University of Vienna)
"The Molecular Basis of Drug-Transporter Interaction- Science or Fiction"
10:15 am - 10:30 amDiscussion
10:30 amCoffee Break
11:00 am - 11:30 amIrwin Arias (National Institutes of Health)
"Adventure in Liverland: The Role of Energy Metabolism in Polarized ABCB11 Trafficking in Hepatocytes"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmJohn D. Schuetz (St. Jude Children's Research Hospital)
"The Metabolome Reveals Precursors of Cholestatic Injury"
12:15 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmNew Ideas and Technologies
Discussion Leader: Tom Rushmore (Thomas Jefferson University)
7:30 pm - 8:00 pmRafel Witek (Life Technologies)
"Liver Cell Culture and Co-Culture Systems for More Relevant Modeling of Liver Physiology"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmRick King (PharmaCadence)
"The Application of Leading Edge LC-MS Technology for the Quantitative Analysis of Enzyme, Substrate and Product from the Same Sample"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmAndrew Kasarskis (Mount Sinai School of Medicine)
"State of the Art and Applications of Modern Nucleic Acid Sequencing and Data Analysis Technologies"
9:20 pm - 9:30 pmDiscussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

This activity is supported by an educational grant from Lilly USA, LLC. For further information concerning Lilly grant funding visit, www.lillygrantoffice.com.
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