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Multi-Drug Efflux Systems
Gordon Research Conference

A Paradigm Shift from Fundamental Mechanisms to Practical Applications

Dates

April 26 - May 1, 2015

Location

Renaissance Tuscany Il Ciocco
Lucca (Barga), Italy

Organizers

Chairs:
Toshihisa Ishikawa & Helen I. Zgurskaya

Vice Chairs:
Suresh V. Ambudkar & Melissa H. Brown

Meeting Description

Transport of solutes (e.g., ions, nutrients and metabolites) across the cellular membrane is a fundamentally important process for living cells to maintain their metabolic homeostasis. Active efflux is a mechanism responsible for moving toxic substances and antibiotics out of the cell; this is considered to be a vital part of xenobiotic metabolism. Multidrug efflux systems display the ability to transport a variety of structurally unrelated substrates from a cell and consequently are capable of conferring resistance to a diverse range of chemotherapeutic agents. The importance of efflux is now broadly recognized in clinical settings as it not only contributes to drug resistance in bacterial and mammalian cells, including cancer, but is also important in drug development efforts as it is a defining factor in drug distribution and elimination in tissues and organs. In addition to the efflux mechanisms, systems controlling the influx of solutes also contribute to multi-drug resistance and xenobiotic metabolism. New roles of influx and efflux in adaptation to various environments and signaling continue to emerge.

Participants of the highly appreciated and productive past meetings on multi-drug efflux systems have made unprecedented progress in the understanding of fundamental mechanisms, diversity and functions of multi-drug efflux systems. The 6th meeting will focus on translating this fundamental knowledge into development of novel therapeutic, diagnostic and bioengineering tools. This conference will address both the efflux and influx systems, as the balance of these two counter flows defines and regulates substrate/drug accumulation in all cells and tissues. The conference will start with two keynote lectures provided by internationally recognized leaders in the field of membrane transporters. Following the keynote lectures, scientific sessions will be held to address the roles and biochemical mechanisms of drug transporters in normal physiology and pathology, in drug discovery and development as well as the emerging roles of drug transporters in stems cells, bioengineering and biofuel production.

For the first time in the history of this meeting, this GRC (April 26 - May 1) will be held in conjunction with the Gordon Research Seminar (GRS) for young scientists (April 25 - 26). For additional information, please kindly visit the GRS web page.

Related Meeting

This GRC was held in conjunction with the "Multi-Drug Efflux Systems" Gordon Research Seminar (GRS). Refer to the associated GRS program page for more information.

Contributors

Meeting Program

Sunday
4:00 pm - 8:00 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: Structure and Function of Multi-Drug Efflux Systems
Discussion Leaders: Herbert Schweizer (University of Florida, USA) and Victor Ling (British Columbia Cancer Research, Canada)
7:40 pm - 7:45 pmIntroduction by Discussion Leader
7:45 pm - 8:25 pmKeynote: Eitan Bibi (Weizmann Institute of Science, Israel)
"Secondary Multidrug Transporters: A Paradigm for Resilience"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 8:40 pmIntroduction by Discussion Leader
8:40 pm - 9:20 pmKeynote: Irwin Arias (Tufts Medical / National Institutes of Health, USA)
"Adventures in Liverland: Cell Biology and Multi-Drug Efflux Systems"
9:20 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmMulti-Drug Efflux Pumps in Health and Diseases
Discussion Leaders: Melissa Brown (Flinders University, Australia) and Mark Warren (Optivia Biotechnology, USA)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:25 amMiguel Viveiros (Institute of Tropical Medicine and Hygiene / New University of Lisbon, Portugal)
"Efflux Modulators as Adjuvants of Anti-Tuberculosis Therapy and Enhancers of Macrophage Killing Activity: A New Concerted Strategy Against Drug Resistant Mycobacterium tuberculosis"
9:25 am - 9:35 amDiscussion
9:35 am - 9:55 amAyush Kumar (University of Manitoba, Canada)
"Triclosan Resistant Mutants Reveal a Complex Regulatory Pathway for AdeIJK Efflux Pump in Acinetobacter baumannii"
9:55 am - 10:05 amDiscussion
10:05 am - 10:25 amIan Paulsen (Macquarie University, Australia)
"An Ace Up Their Sleeve: A Novel Family of Drug Efflux Systems Represented by the AceI Exporter"
10:25 am - 10:35 amDiscussion
10:35 am - 11:00 amCoffee Break
11:00 am - 11:05 amIntroduction by Discussion Leader
11:05 am - 11:25 amMatthias Schwab (Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, Germany)
"Regulation of MCT4 by DNA Methylation of the SLC16A3 Promoter and Clinical Outcome"
11:25 am - 11:35 amDiscussion
11:35 am - 11:55 amJohn Schuetz (St. Jude Children's Research Hospital, USA)
"Cyclic Nucleotide Compartmentalization: Contributions of Phosphodiesterases and ABC Transporters"
11:55 am - 12:05 pmDiscussion
12:05 pm - 12:25 pmVerena Keitel (University of Dusseldorf, Germany)
"Bile Acid Transport in Health and Disease"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmFunctional Interactions Between Influx and Efflux in Health and Clinical Conditions
Discussion Leader: Susan Cole (Queen's University, Canada)
6:00 pm - 6:05 pmIntroduction by Discussion Leader
6:05 pm - 6:25 pmTappei Takada (The University of Tokyo Hospital, Japan)
"Functional Cooperation of URAT1/SLC22A12, GLUT9/SLC2A9 and BCRP/ABCG2 in Urate Transport"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmJashvant Unadkat (University of Washington, USA)
"The Role of Quantitative Proteomics in Understanding Inter-Individual Variability in Transporter-Mediated Drug Disposition"
6:55 pm - 7:05 pmDiscussion
7:05 pm - 7:25 pmDeanna Kroetz (University of California, San Francisco, USA)
"Influence of ABC Transporter Genetic Variation and Chemotherapy Response and Toxicity"
7:25 pm - 7:35 pmDiscussion
7:35 pm - 7:55 pmHendrik van Veen (University of Cambridge, United Kingdom)
"Expression and Study of Multidrug Transporters in Lactococcus lactis"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Tuesday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmRole of Multi-Drug Efflux in Drug Discovery and Development
Discussion Leader: Juerg Dreier (Basilea Pharmaceutica International Ltd., Switzerland)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:25 amPer Artursson (Uppsala University, Sweden)
"A Proteomics Informed Approach for Integrated Prediction of Drug Uptake, Metabolism and Efflux"
9:25 am - 9:35 amDiscussion
9:35 am - 9:55 amLarry Sklar (University of New Mexico, USA)
"High Throughput Screening of Efflux Inhibitors"
9:55 am - 10:05 amDiscussion
10:05 am - 10:25 amKim Brouwer (University of North Carolina, Chapel Hill, Eshelman School of Pharmacy, USA)
"Sandwich-Cultured Hepatocytes: A Screening Tool to Assess Hepatobiliary Drug Transport, Transporter-Based Drug-Drug Interactions (DDIs), and Hepatotoxicity"
10:25 am - 10:35 amDiscussion
10:35 am - 11:05 amCoffee Break
11:05 am - 11:25 amOlga Lomovskaya (The Medicines Company, USA)
"Development of Efflux Pump Inhibitors"
11:25 am - 11:35 amDiscussion
11:35 am - 11:55 amTimothy Opperman (Microbiotix, Inc, USA)
"A Novel Class of RND Efflux Pump Inhibitors"
11:55 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSelected from Poster Abstracts: Lora Deuitch (Karolinska Institute, Sweden)
"The Specificity and Utility of the ABCG2 Inhibitor Ko143 for PET Imaging"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Pranav Puri (University of Amsterdam, The Netherlands)
"Fluorescence Microscopy Approach to Study Assembly and Activity of RND Type Multidrug Efflux Machine from E.coli"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmStructure and Molecular Dynamics of Membrane Transporters
Discussion Leader: Paolo Ruggerone (University of Cagliari, Italy)
6:00 pm - 6:05 pmIntroduction by Discussion Leader
6:05 pm - 6:25 pmOsamu Nureki (University of Tokyo, Japan)
"Dynamic Structure of MATE Drug Exporter and Its Inhibitor Design"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmChristian Kandt (Bonn-Rhein-Sieg University of Applied Sciences, Germany)
"Antibiotics Resistance: Insights from Molecular Dynamics Simulations"
6:55 pm - 7:05 pmDiscussion
7:05 pm - 7:25 pmIan Kerr (University of Nottingham, United Kingdom)
"Investigation of ABCG2 Oligomerization and Dynamics Using Fluorescence Microscopy"
7:25 pm - 7:35 pmDiscussion
7:35 pm - 7:55 pmKlaas Pos (Goethe University Frankfurt, Germany)
"Structural and Functional Insights into the AcrB Multidrug Efflux Pump"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmStructure-Function Relationships in Multi-Drug Efflux Pumps from Microbes and Human
Discussion Leader: Peter Henderson (University of Leeds, United Kingdom)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:25 amVassiliy Bavro (University of Birmingham, United Kingdom)
"Mechanism and Assembly of Tri-Partite Efflux Pumps"
9:25 am - 9:35 amDiscussion
9:35 am - 9:55 amIris Maldener (University of Tuebingen, Germany)
"Structure-Function Analysis of a Tripartite Glycolipid Efflux Pump from Multicellular Cyanobacteria"
9:55 am - 10:05 amDiscussion
10:05 am - 10:25 amDavid Hooper (Massachusetts General Hospital, USA)
"Regulation and Function of Efflux Pumps in Staphylococcus aureus"
10:25 am - 10:35 amDiscussion
10:35 am - 11:00 amCoffee Break
11:00 am - 11:20 amJean-Michel Jault (The Institute of Biology and Chemistry of Proteins, CNRS, France)
"The Functioning Mechanism of Bacterial Multidrug ABC Transporters Probed by H/D Exchange"
11:20 am - 11:30 amDiscussion
11:30 am - 11:50 amCedric Govaerts (Free University of Brussels, Belgium)
"Protonation-Driven Conformational Switch in the Multidrug Transporter LmrP"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:20 pmJohn Golin (Catholic University of America, USA)
"ABC Transporters as One-Way Gates (Molecular Diodes): The Case for Pdr5, a Major Yeast Multidrug Pump"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmProtein Expression, Folding, and Membrane Trafficking of Membrane Transporters
Discussion Leader: Frances Sharom (University of Guelph, Canada)
6:00 pm - 6:05 pmIntroduction by Discussion Leader
6:05 pm - 6:25 pmYinan Wei (University of Kentucky, USA)
"Life of an AcrB Trimer in the Cell Membrane"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmSuresh Ambudkar (National Cancer Institute / National Institutes of Health, USA)
"Role of Residues in the Intracellular Loops in Folding and Maturation of Human ABCB1 and the Mechanism of Rescue by Chaperones"
6:55 pm - 7:05 pmDiscussion
7:05 pm - 7:25 pmAnne Nies (Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Germany)
"Functional Characterization of Common Protein Variants of Human ABCC11 and Their Clinical Impact"
7:25 pm - 7:30 pmDiscussion
7:30 pm - 7:40 pmSelected from Poster Abstracts: Isabelle Mus-Veteau (CNRS, University of Nice Sophia Antipolis, France)
"The Human Hedgehog Receptor Patched: A New Drug Efflux Pump Involved in Chemotherapy Resistance"
7:40 pm - 7:45 pmDiscussion
7:45 pm - 7:55 pmSelected from Poster Abstracts: Martin Picard (CNRS, Paris Descartes University, France)
"In Vitro Activity of the Fully Assembled MexAB-OprM Efflux Pump from Pseudomonas aeruginosa"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Thursday
7:30 am - 8:30 amBreakfast
8:30 am - 9:00 amBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
9:00 am - 12:30 pmMulti-Drug Efflux Pumps in Environment, Bioengineering and Biofuel Production
Discussion Leader: Aixin Yan (The University of Hong Kong, Hong Kong, China)
9:00 am - 9:05 amIntroduction by Discussion Leader
9:05 am - 9:25 amWendy Peer (University of Maryland, USA)
"Trafficking of ABCB Hormone Transporters Is Regulated by Sphingolipids and Stress-Responsive Endocytosis"
9:25 am - 9:35 amDiscussion
9:35 am - 9:55 amAnne-Brit Kolsto (University of Oslo, Norway)
"Efflux in the Bacillus cereus Group"
9:55 am - 10:05 amDiscussion
10:05 am - 10:25 amTwan Lammers (RWTH Aachen University, Germany)
"Nanomedicine Formulations for Overcoming Multi-Drug Resistance"
10:25 am - 10:35 amDiscussion
10:35 am - 11:05 amCoffee Break
11:05 am - 11:25 amAindrila Mukhopadhyay (Lawrence Berkeley National Laboratory, USA)
"Engineering Microbial Biofuel Tolerance and Export Using Efflux Pumps"
11:25 am - 11:35 amDiscussion
11:35 am - 11:55 amAixin Yan (The University of Hong Kong, Hong Kong, China)
"Physiological Roles of Drug Efflux Pumps in Environmental Stress Adaptation in E. coli"
11:55 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSelected from Poster Abstracts: Bohnert Juergen (Jena University Hospital, Germany)
"Association of AcrAB-TolC Activity in Escherichia coli Sepsis Isolates"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Erika Boulant (Aix-Marseille University, France)
"Efflux Pumps as Tools to Increase Biofuel Tolerance in Bacteria"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmTransporters in Stem Cells and Clinical Implications
Discussion Leader: Susan Bates (National Cancer Institute, USA)
6:00 pm - 6:05 pmIntroduction by Discussion Leader
6:05 pm - 6:25 pmBalazs Sarkadi (Hungarian Academy of Sciences, Hungary)
"Role of ABCG2 and ABCB1 in Stem Cell Biology"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:55 pmBrian Sorrentino (St. Jude Children's Research Hospital, USA)
"Progeny Tracking Studies To Trace the Origin and Contribution of ABCG2+ Stem Cells in Adult and Developing Mice"
6:55 pm - 7:05 pmDiscussion
7:05 pm - 7:25 pmSusan Bates (National Cancer Institute, USA)
"Cancer Stem Cells: Lost in Translation"
7:25 pm - 7:35 pmDiscussion
7:35 pm - 7:45 pmAnika Hartz (University of Kentucky, USA)
"ABCB1 News: The Transporter and the Amyloid"
7:45 pm - 7:50 pmDiscussion
7:50 pm - 8:00 pmClosing Remarks
8:00 pmDinner
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible [in part] by 1 R13 AI115728-01 from the National Institute of Allergy and Infectious Diseases. 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 of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
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