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Conference Program
 
Drug Metabolism
After Forty Years of Inquiry: An Era of Engineered Enzymes and Individualized Drug Therapies
July 11-16, 2010
Holderness School
Holderness, NH
Chair:
Kenneth E. Thummel

Vice Chair:
Scott R. Obach

Drug metabolism and transport are often major sources of inter-individual variability in drug response. Past approaches to managing this biological reality have been to either develop drugs with a wide safety margin or to monitor the patient and adjust doses accordingly. However, decades of research have revealed some of the genetic and environmental causes of variable drug clearance and now promises a new era of individualized drug therapy. Moreover, detailed understanding of reaction mechanisms and structure-activity relationships is opening the door to rational engineering of enzymes for therapeutic and drug development process applications, including the creation of bioreactors for large-scale metabolite synthesis. Recent advances in these and other related research areas form the foundation of this 40th anniversary, 2010 Gordon Conference: “After Forty Years of Inquiry: An Era of Engineered Enzymes and Individualized Drug Therapies”. As in past years, the overall goal of this conference will be to create a collegial atmosphere for both senior and junior scientists in academia and industry to explore the limits of our science, chart new directions that move us beyond existing boundaries, and to create new friendships and collaborations within and across disciplines that will make it a reality. The program will follow the traditional GRC Drug Metabolism format with the keynote lecture Sunday evening, 4 morning sessions with 4 speakers each, 3 evening sessions with 3 speakers each, and Wednesday evening 6 graduate students and postdoctoral fellows will make oral presentations selected from the outstanding posters submitted. Participants are encouraged to submit poster presentations, with the sessions organized by Vice Chair Scott Obach.

Note that housing and meals are included in the registration fee. Also, the remodeled dining hall and poster presentation room at Holderness is fabulous. Come join us in New Hampshire!


Contributors

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 - 7:50 pmWelcome: Tim Tracy (University of Minnesota), filling in for Ken Thummel
7:50 pm - 9:30 pmOpening Session - After Forty Years of Inquiry: A New Era of Engineered Enzymes and Individualized Drug Therapies
7:50 pm - 9:00 pm Bryan Dechairo (Medco Health Solutions, Inc)
"Pharmacogenetics: Bench to Bedside Becomes a Reality"
9:00 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
8:45 amGroup Photo
9:00 am - 12:30 pmIntegrative Approaches to Identify Genetic Determinants Responsible for Human Variation in Drug Response and Toxicity
Discussion Leader: Erin Schuetz (St Jude Children's Research Hospital)
9:00 am - 9:30 am Xia Yang (Sage Bionetworks)
"Integrative Genomics Approaches to Identify Regulators of Hepatic ADME gene Expression"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Danxin Wang (The Ohio State University)
"Structural RNA Polymorphisms (srSNPs) Affecting RNA Processing and Translation"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Steve Strom (University of Pittsburgh)
"Humanized Mice and Stem Cell-Derived Hepatocytes: New Technologies for Basic Research"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Alison Harrill (The Hamner Institute for Health Sciences)
"Collaborative Cross Inbred Mice as a Model for Idiosyncratic Adverse Drug Events"
12:15 pm - 12:30 pm Discussion
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 pmVariability in Drug Metabolism: Looking Beyond the Genes Encoding Drug Metabolizing Enzymes
Discussion Leader: Andrea Gaedigk (Mercy Medical Center - Kansas City)
7:30 pm - 8:00 pm Uli Zanger (Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology)
"Pathway-oriented and Genome-wide Analysis of the Hepatic Cytochrome P450 System: The Quest for Factors Impacting Variability"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Xiao-bo Zhong (University of Kansas)
"Epigenetic Control of CYP3A Expression in the Fetus and Post-Partum"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Aiming Yu (SUNY-Buffalo)
"Role of MicroRNAs in the Regulation of Drug Metabolism and Disposition"
9:20 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmBiotransformation Mechanisms: New Concepts and Understudied Enzymes
Discussion Leader: Jeff Jones (Washington State University)
9:00 am - 9:30 am Silke LeimKühler (University of Potsdam)
"Expression, and Mechanism of Mammalian Aldehyde Oxidases"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Philip M. Potter (St Jude Children's Research Hospital)
"Rationale Prodrug Design using Esterases"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Dan Rock (Amgen)
"Potential Drug Interactions with P450 Reductase Supported Indoleamine 2,3-Dioxygenase"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Bill Atkins (University of Washington)
"4-Hydroxy-2-nonenal Metabolism by Glutathione S-Transferases"
12:15 pm - 12:30 pm Discussion
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 pmUse of DME Enzymes for Therapeutic and Metabolite Synthesis Applications
Discussion Leader: Tom Rushmore (Invitrogen/Lifetech)
7:30 pm - 8:00 pm Fred Fleitz (Independent Consultant)
"Efficient Synthesis of Metabolites via Isolated P450s"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Nico Vermeulen (Vrije Universiteit)
"Tailoring Cytochrome P450 BM3 for Drug Discovery and Safety Purposes"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm David Waxman (Boston University)
"Cancer Chemotherapy and Drug Metabolism: Targeting Tumor Cells and Tumor-associated Endothelial Cells"
9:20 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmThe Role of Protein-Protein Interactions on Cytochrome P450 Function
Discussion Leader: Wayne Backes (Louisiana State University)
9:00 am - 9:30 am Lucy Waskell (University of Michigan)
"The Interaction of Cytochrome P450 2B4 with Its Redox Partners"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Tim Tracy (University of Minnesota)
"Protein-protein Interactions Between P450s: A Potential Modulator of Drug Metabolizing Activity"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Alan Conley (University of California - Davis)
"Steroidogenesis: Organizing Chaos in Membranes"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Wayne Backes (Louisiana State University)
"Homomeric and Heteromeric P450 Complexes Affect Monooxygenase Function"
12:15 pm - 12:30 pm Discussion
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)
7:30 pm - 7:45 pm Xia Wen (Rutgers University)
"Renal MRP2 Transporter Protects Against Cisplatin Toxicity"
7:45 pm - 7:50 pm Discussion
7:50 pm - 8:05 pm Annie Albin Lumen (Drexel University)
"Mass Action Kinetic Model: A Sensitive Tool in Identifying other Kinetically Relevant Transporters in Expression Systems that Over Express P-glycoprotein"
8:05 pm - 8:10 pm Discussion
8:10 pm - 8:25 pm Kelsey Hansen (University of Washington)
"Characterization of the Mechanism-Based Inhibition of Cytochrome P450 3A4 by Resveratrol: Evidence for Heme Destruction and Covalent Binding to CYP3A4 Protein"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:45 pm Daniel Ferreira (University of Connecticut)
"Vanin-1 Deficient Mice Have Enhanced Susceptibility to Acetaminophen-Induced Hepatotoxicity"
8:45 pm - 8:50 pm Discussion
8:50 pm - 9:05 pm Upendra Dahal (Washington State University)
"Metabolism of Type II Binding Compounds by Cytochrome P450 3A4 via Direct Reduction of Iron"
9:05 pm - 9:10 pm Discussion
9:10 pm - 9:25 pm Ian Cook (University of Alabama, Birmingham)
"SULT1A1 Structural Rearrangements Elicited by PAPS Binding Alter Substrate Specificity"
9:25 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmTransporter Biology: Impact on Drug Distribution and Organ Toxicity
Discussion Leader: Susan Cole (Queens University Cancer Research Institute)
9:00 am - 9:30 am Brian Houston (University of Manchester)
"Methodology for Development of a Physiological Model Incorporating CYP3A and P-glycoprotein for the Prediction of Drug Interactions"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Christopher MacLauchlin (Glaxo Smith Kline)
"The Role of Hepatic Transporters in the Mechanisms of Lapatinib Hepatotoxicity"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am David Goldman (Albert Einstein College of Medicine)
"The Role of Folate Transporters in Folate Homeostasis and Antifolate Activities"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Susan Cole (Queens University Cancer Research Institute)
"Determinants of Conjugated Metabolite Interactions with MRP (ABCC) Transporters"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmReception
6:00 pmDinner
7:30 pm - 9:30 pmNew Innovations to Overcome Pre-clinical Metabolic Liabilities in Drug Development
Discussion Leader: Larry Wienkers (Amgen)
7:30 pm - 8:00 pm Scott Harbeson (Concert Pharmaceuticals)
"Improvements in Metabolic Stability and Pharmacokinetic Properties with Deuterium-labeling of Drug Candidates"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Robert Lyon (Seattle Genetics)
"Circumventing ADME Liabilities by Targeted Drug Deliver with Monoclonal Antibodies"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Marlou van Iersel (Organon/Schering)
"Overcoming the Hepatic First-Pass Effect with Sublingual Administration: A Case Study with Asenapine"
9:20 pm - 9:30 pm Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Last Updated: July 22, 2010
 
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