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Drug Metabolism
Gordon Research Conference

The Precision Medicine Revolution: New Frontiers for Scientists in Drug Metabolism, Transport and Pharmacokinetics

Dates

July 10-15, 2016

Location

Holderness School
Holderness, NH

Organizers

Chair:
Kim L.R. Brouwer

Vice Chair:
Donavon J. McConn

Meeting Description

The 21st century approach to discovering highly selective medicines and developing treatment strategies and therapeutic regimens for individual patients is undergoing revolutionary changes. Industry, academic and regulatory scientists with interests in drug metabolism, transporters, pharmacokinetics and related disciplines will gather at the 46th Drug Metabolism Gordon Research Conference to explore exciting new frontiers in the quest to achieve more precise tailoring of medicines. Young investigators, including postdoctoral fellows and graduate students, will interact with academic and industry thought leaders in an informal setting. The collegial nature of this conference, and the opportunity to learn, discuss unpublished research, share ideas, and establish collaborations, have made this venue a favorite in the drug metabolism community. The 2016 conference will focus on transformative approaches in the discovery and development of targeted therapies for inherited and acquired diseases, and advances in assessing disease treatment and predicting optimal therapy and regimens from a DMPK perspective. Sessions will include advances in endogenous biomarkers, orphan P450s, designing targeted covalent inhibitors, drug transporters, pharmacokinetic strategies, renal models, and challenges in the precision medicine era. Each presentation will include unpublished data and expert opinions to stimulate audience discussion. Attendees are encouraged to submit posters. The Wednesday evening program features oral presentations by young investigators selected from the submitted posters. With scientific sessions in the mornings and evenings, the afternoons are set aside for attendees to enjoy the many outdoor recreational activities in the New Hampshire area. Afternoon "traditions" of this conference include an Academia vs. Industry softball game (no experience necessary!), and hiking and kayaking/canoeing outings in the White Mountains. The registration fee includes all meals and housing on the picturesque Holderness School campus. We hope that you will join us for an outstanding meeting focused on rapidly advancing frontiers in drug metabolism science as we deliver on the promise of precision medicine!

Contributors

Final Meeting Program

Sunday
2:00 pm - 9:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKeynote Session: New Frontiers for DMPK in Precision Medicine
Discussion Leader: Kim Brouwer (University of North Carolina at Chapel Hill, USA)
7:40 pm - 7:55 pmOpening Remarks
7:55 pm - 8:55 pmAllan Rettie (University of Washington, USA)
"Drug Metabolism Contributions to 'Precision Medicine': Past, Present, Future"
8:55 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmAdvances in Precision Medicine: Endogenous Biomarkers
Discussion Leader: John Wagner (Takeda Pharmaceuticals, USA)
9:00 am - 9:20 amJohn Wagner (Takeda Pharmaceuticals, USA)
"Advances in Precision Medicine: Why Do We Need a Multi-Stakeholder Process?"
9:20 am - 9:30 amDiscussion
9:30 am - 10:05 amShashi Amur (U.S. Food and Drug Administration, USA)
"Biomarker Qualification: Toward a Multi-Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization"
10:05 am - 10:20 amDiscussion
10:20 am - 10:50 amCoffee Break
10:50 am - 11:25 amRima Kaddurah-Daouk (Duke University Health System, USA)
"Metabolomic Signatures for Drug Response Phenotypes-Pharmacometabolomics Enables Precision Medicine"
11:25 am - 11:40 amDiscussion
11:40 am - 12:15 pmFrank Sistare (Merck & Co., Inc., USA)
"Identification, Application, and Regulatory Qualification of New Translational Biomarkers for Improved Safety Assessment in Drug Development"
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 pmClinical and Real World Applications of Precision Medicine
Discussion Leader: Rebecca Blanchard (Merck & Co., Inc., USA)
7:30 pm - 7:40 pmIntroduction by Discussion Leader
7:40 pm - 8:00 pmDermot Reilly (Merck Research Laboratories, USA)
"Association Analysis of Low Frequency Genetic Variation with Liver Triglyceride Content and Related Endpoints in a Multi-Ethnic Cohort"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:30 pmSara Van Driest (Vanderbilt University, USA)
"The Electronic Medical Record as a Tool for Precision Medicine Research and Implementation"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 9:00 pmCliona Molony (Pfizer, USA)
"Mining Real-World Data for Precision Medicine in Drug Discovery"
9:00 pm - 9:10 pmDiscussion
9:10 pm - 9:30 pmGeneral Discussion
Tuesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmOrphan P450s: Discovery of Function and Relevance to Applications in Medicine
Discussion Leader: F. Peter Guengerich (Vanderbilt University School of Medicine, USA)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:30 amF. Peter Guengerich (Vanderbilt University School of Medicine, USA)
"The General Problem of Gene Annotation and Its Significance with P450s: Deorphanization of Several Human P450s"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amEdward Kelly (University of Washington, USA)
"P450 4V2 and Its Role in Vision"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:30 amKevin Johnson (Vanderbilt University School of Medicine, USA)
"CYP27C1 Catalyzes the Desaturation of Vitamin A1 to Vitamin A2"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmJohn Stegeman (Woods Hole Oceanographic Institution, USA)
"Use of Fish Models in Deorphanization of P450s"
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 pmTargeted Covalent Inhibitors – Risks, Benefits, and Promise for Precision Medicine
Discussion Leader: Thomas Baillie (University of Washington, USA)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmThomas Baillie (University of Washington, USA)
"Reversible and Irreversible Covalent Drugs for Precision Medicine – Therapeutic Promise Versus Toxicological Risk"
7:55 pm - 8:10 pmDiscussion
8:10 pm - 8:35 pmDeqiang Niu (Celgene Avilomics Research, USA)
"The Discovery of Rociletinib (CO-1686): An Example of Engineering Selectivity into EGFR Covalent Inhibitors"
8:35 pm - 8:50 pmDiscussion
8:50 pm - 9:15 pmJohn Kath (Pfizer Global Research and Development, USA)
"Reducing Proteome Reactivity of Irreversible EGFR T790M Inhibitors"
9:15 pm - 9:30 pmDiscussion
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmTransporters: To Precision and Beyond
Discussion Leader: Sonia de Morais (AbbVie Inc., USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:40 amAllan Wolkoff (Jack and Pearl Resnick Campus, Albert Einstein College of Medicine, USA)
"Intracellular Trafficking of Drug Transporters"
9:40 am - 9:55 amDiscussion
9:55 am - 10:20 amBo Feng (Pfizer, USA)
"Predicting Human Brain Penetration from In Vitro Transporter Studies"
10:20 am - 10:35 amDiscussion
10:35 am - 11:05 amCoffee Break
11:05 am - 11:30 amAleksandra Galetin (University of Manchester, United Kingdom)
"PBPK for Drug Transporters - What Is Missing?"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmKathleen Giacomini (University of California, San Francisco, USA)
"Clinical Relevance of Drug Transporters – Enabling Precision 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 in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
7:30 pm - 9:30 pmYoung Investigator Presentations
Session in honor of Dr. Richard Okita.
Discussion Leader: Henry Strobel (University of Texas Medical School at Houston, USA)
7:30 pm - 7:45 pmIntroduction by Discussion Leader
7:45 pm - 7:55 pmIzna Ali (University of North Carolina at Chapel Hill, USA)
"Identification of Novel MRP3 Inhibitors Based on Computational Models and Verification Using an In Vitro Membrane Vesicle Assay"
7:55 pm - 8:00 pmDiscussion
8:00 pm - 8:10 pmSara Humphreys (Washington State University, USA)
"Novel Time-Resolved Three-Dimensional Approach to Quantify Passive Diffusion Rates of Drug-Like Compounds Across MDCK Monolayers at Sub-Cellular Resolution"
8:10 pm - 8:15 pmDiscussion
8:15 pm - 8:25 pmErkka Järvinen (University of Helsinki, Finland)
"MRP3 Is More Efficient than MRP2 in Transporting Small Bicyclic Planar Glucuronides"
8:25 pm - 8:30 pmDiscussion
8:30 pm - 8:40 pmBryan Mackowiak (University of Maryland School of Pharmacy, USA)
"Prototypical CAR Antagonist PK11195 Is Metabolized to a CAR Activator in Physiologically-Relevant Cellular Systems"
8:40 pm - 8:45 pmDiscussion
8:45 pm - 8:55 pmTing Wang (Albert Einstein College of Medicine, USA)
"Isozyme Specific Allosteric Regulation of Human Sulfotransferase 1A1 – Structure and Mechanism"
8:55 pm - 9:00 pmDiscussion
9:00 pm - 9:10 pmDahea You (Rutgers University, USA)
"Enhanced Histone Acetylation Up-Regulates MDR1 and BCRP Transporters in Human Blood-Brain Barrier Cells"
9:10 pm - 9:15 pmDiscussion
9:15 pm - 9:30 pmGeneral Discussion
Thursday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmNew Frontiers for Predicting Renal Toxicity and Clearance, and Applications in Precision Medicine
Discussion Leader: Deanna Kroetz (University of California, San Francisco, USA)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:30 amDeanna Kroetz (University of California, San Francisco, USA)
"Prediction of Renal Drug Clearance and Toxicity with a Biomimetic Microfluidics Platform"
9:30 am - 9:45 amDiscussion
9:45 am - 10:15 amBenjamin Freedman (University of Washington, USA)
"iPSC-Derived Human Kidney Organoids: Platforms for Disease Modeling and Therapeutics Testing"
10:15 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:30 amVishal Vaidya (Harvard Medical School, USA)
"Early Biomarkers of Human Renal Injury"
11:30 am - 11:45 amDiscussion
11:45 am - 12:15 pmAdrian Ray (Gilead Sciences, Inc., USA)
"Improved Prediction of Renal Drug-Drug Interactions"
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 pmPrecision Medicine: Why It Works, Why It Has Not Worked, and Strategies to Overcome Barriers
Discussion Leader: Bob Powell (UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmBob Powell (UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA)
"Precision Medicine: Why It Works, Why It Has Not Worked, and Strategies to Overcome Barriers - Principles and Case Studies"
7:55 pm - 8:10 pmDiscussion
8:10 pm - 8:35 pmRichard Peck (F. Hoffmann La Roche, Switzerland)
"Precision Medicine: Successes, Challenges Opportunities, Ideas - A Personal Perspective (from Someone in Industry)"
8:35 pm - 8:50 pmDiscussion
8:50 pm - 9:15 pmYaning Wang (U.S. Food and Drug Administration, USA)
"Precision Medicine: Mission of FDA Clinical Pharmacology"
9:15 pm - 9:30 pmDiscussion
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible (in part) by 1 R13 TR 001691-01 from the National Center for Advancing Translational Sciences (NCATS). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
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