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Multi-Drug Efflux Systems
Gordon Research Conference

Integrated Approaches to Understanding the Role of Multi-Drug Efflux Systems in Health and Disease

Dates

March 26-31, 2017

Location

Hotel Galvez
Galveston, TX

Organizers

Chairs:
Suresh V. Ambudkar & Melissa H. Brown

Vice Chairs:
Deanna L. Kroetz & Miguel Viveiros

Meeting Description

Cancer is the second-highest cause of mortality in the developed world, while infectious diseases are the second-highest cause of death in the developing world. In individuals affected by cancer and infectious diseases, development of resistance to drugs is a serious problem and drug efflux transporters are known to contribute significantly to this phenomenon. Multidrug resistance (MDR) transporters are present ubiquitously throughout nature, from bacteria to humans. This widespread distribution and the promiscuous nature of MDR efflux pumps has been taken into consideration when preparing the program and selecting presenters. We will focus on recent developments in unraveling the molecular mechanisms of polyspecificity and transport based on biochemical, genomic, pharmacological and structural studies. Many other aspects such as cellular mechanisms that regulate the activity and/or expression of MDR transporters, the physiological functions of MDR transporters in various organisms and their pathophysiological functions in humans will also be presented by leading researchers from academic institutions and pharmaceutical companies from all over the world. In addition, novel strategies for the development of potent antibacterials and modulators will be covered. Various preclinical and clinical strategies to improve clinical outcomes will be discussed. Special emphasis will be given to the use of "omics" and "meta" systemic approaches to study membrane transporters as well as the impact of the microbiome in health and disease. This powerful combination of topics will facilitate greater understanding and collaboration between researchers investigating these topics. It is expected that the broad range of topics combined with informal scientific interactions at the conference will result in an exchange of information in a relaxed environment, and application of many new ideas and approaches to the complex problem of drug resistance in both microbes and humans. Preceding this conference, there will be a Gordon Research Seminar for young scientists, post-doctoral fellows and graduate students.

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: Regulation and Function of Multidrug Efflux Systems
Discussion Leaders: Michael Gottesman (National Cancer Institute, NIH, USA) and Olga Lomovskaya (The Medicines Company, USA)
7:40 pm - 7:45 pmIntroduction by Discussion Leader
7:45 pm - 8:25 pmSusan Cole (Queen's University, Canada)
"MRP/ABCC Drug Transporters in Human Health and Disease"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 8:40 pmIntroduction by Discussion Leader
8:40 pm - 9:20 pmWilliam Shafer (Emory University School of Medicine, USA)
"Regulation of Efflux Pump Genes in Neisseria gonorrhoeae: Linkage of Antimicrobial Resistance with Pathogens"
9:20 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmStructural Basis of the Mechanism of MDR Pumps
Discussion Leaders: Guillermo Altenberg (Texas Tech University Health Sciences Center, USA) and Rajeev Misra (Arizona State University, USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:30 amVassilis Koronakis (University of Cambridge, United Kingdom)
"Protein and Drug Secretion by Tripartite Efflux Pumps"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amDi Xia (National Cancer Institute, NIH, USA)
"Coupling of Helix Movement of TMDs with Opening and Closing of Two Halves of P-Glycoprotein"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amIna Urbatsch (Texas Tech University Health Sciences Center, USA)
"Interactions and Cooperativity Between P-Glycoprotein Structural Domains Determined by Thermal Uncoupling"
10:30 am - 10:40 amDiscussion
10:40 am - 11:00 amCoffee Break
11:00 am - 11:20 amEdward Yu (Iowa State University, USA)
"The AbgT Family: A Novel Class of Antimetabolite Transporters"
11:20 am - 11:30 amDiscussion
11:30 am - 11:50 amMikio Tanabe (High Energy Accelerator Research Organization (KEK), Japan)
"Structural Insights into the Conformational Switching Mechanism of a Secondary Multidrug/Proton Antiporter"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSuneet Shukla (National Cancer Institute, NIH, USA)
"Cryo-EM Analysis of Conformational Landscape of P-Glycoprotein"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Lutz Schmitt (Heinrich Heine University Duesseldorf, Germany)
"Towards an In Vitro Characterization of the Yeast ABC Transporter Pdr5"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
3:00 pm - 4:00 pmPower Hour
The GRC Power Hour is an optional informal gathering open to all meeting participants. It is designed to help address the challenges women face in science and support the professional growth of women in our communities by providing an open forum for discussion and mentoring.
Organizers: Susan Bates (Columbia University, USA) and Helen Zgurskaya (University of Oklahoma, USA)
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmInflux and Efflux Systems-Similarities and Differences
Discussion Leader: John Schuetz (St. Jude Children's Research Hospital, USA)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmBert Poolman (University of Groningen, The Netherlands)
"Ensemble and Single Molecule Studies of ABC Importers and New Membrane Model Systems to Probe ATP-Dependent Transport"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:25 pmNavjot Pabla (Ohio State University, USA)
"Post-Translational Regulation of Drug Transporters"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 8:55 pmHerbert Schweizer (University of Florida, USA)
"Differential Regulation of the Burkholderia pseudomallei BpeEF-OprC Efflux Pump Determines Drug Resistance Profile"
8:55 pm - 9:05 pmDiscussion
9:05 pm - 9:25 pmSelected from Poster Abstracts: Inga Leus (University of Oklahoma, USA)
"Functional Interplay Between Active Efflux and Antibiotic Oermeability Barriers in Acinetobacter baumannii"
9:25 pm - 9:30 pmDiscussion
Tuesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmOmics and Meta Systemic Approaches
Discussion Leaders: Miguel Viveiros (Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal) and Eitan Bibi (Weizmann Institute of Science, Israel)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:30 amCaroline Lee (National University of Singapore, Singapore)
"Genomic Approach Towards Predicting Drugs Exhibiting Population Differences in Response"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amKarl Hassan (University of Leeds, United Kingdom)
"Functional Genomics in the Discovery and Characterization of Efflux Pumps in Acinetobacter baumannii"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amD. Branch Moody (Harvard Medical School, USA)
"Lipidomic Dissection of the Mycobacterium tuberculosis Cell Wall"
10:30 am - 10:40 amDiscussion
10:40 am - 11:00 amCoffee Break
11:00 am - 11:20 amYu Toyoda (The University of Tokyo Hospital, Japan)
"ABCC2-Mediated Biliary Excretion of Glutathione Conjugates of 1,2-Dichloropropane Evidenced by Untargeted Metabolomics"
11:20 am - 11:30 amDiscussion
11:30 am - 11:50 amPer Artursson (Uppsala University, Sweden)
"The Quantitative Transporter Proteome and Its Application in Prediction of Drug Disposition"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSelected from Poster Abstracts: Henrietta Venter (University of South Australia, Australia)
"Reversing Antimicrobial Resistance with Efflux Pump Inhibitors"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Reinke Müller (Goethe University Frankfurt, Germany)
"AcrB-Inactivation and Reactivation via Switch Loop Manipulation"
12:25 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 pmMolecular Basis of Polyspecificity of the Multidrug Transporters
Discussion Leader: John Golin (Catholic University of America, USA)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmKarl Kuchler (Medical University of Vienna, Austria)
"A Mechanism for ABCG2-Mediated Drug Efflux: A Tale of Many Mutants"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:25 pmMegan O'Mara (The Australian National University, Australia)
"Multidrug Transporter Simulations: Can We Learn New Tricks from Old Drugs?"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 8:55 pmRaymond Turner (University of Calgary, Canada)
"Defining the Export Pathway of EmrE: A Bacterial Small Multidrug Efflux Pump"
8:55 pm - 9:05 pmDiscussion
9:05 pm - 9:25 pmRajeev Misra (Arizona State University, USA)
"Mechanistic Insights into a Multidrug Transporter"
9:25 pm - 9:30 pmDiscussion
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmStrategies for Development of New Antibacterials and Modulators
Discussion Leaders: Zhe-Sheng (Jason) Chen (St. John's University, USA) and Satoshi Murakami (Tokyo Institute of Technology, Japan)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:30 amGerhard Ecker (University of Vienna, Austria)
"Leveraging Open Data for Development of ABC Transporter Inhibitors"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amMark Blaskovich (The University of Queensland, Australia)
"Microscopic to Macroscopic Investigations of Gram-Negative Bacterial Penetration"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amThomas Efferth (Johannes Gutenberg University of Mainz, Germany)
"From In Silico Prediction to Rational Drug Design to Fight MDR"
10:30 am - 10:40 amDiscussion
10:40 am - 11:00 amCoffee Break
11:00 am - 11:20 amGlenn Kaatz (Wayne State University School of Medicine, USA)
"Evaluation of Natural and Synthetic Compounds as NorA Inhibitors"
11:20 am - 11:30 amDiscussion
11:30 am - 11:50 amRuben Tommasi (Entasis Therapeutics, USA)
"Improving Our Understanding of Porin Permeability in Gram-Negative Bacteria"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSelected from Poster Abstracts: Megumi Obara (Tohoku University Graduate School of Medicine, Japan)
"Discovering Potent ABCB1 Inhibitors by High-Throughput Screening from 5760 Compounds in Tohoku University Chemical Library"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Julia Sachs (Technical University of Cologne, Germany)
"Pharmacological Inhibition of the P-gp Transporter by Goniothalamin Derivatives Sensitizes Resistant Cancer Cells to Chemotherapy"
12:25 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 pmMicrobiome in Health and Diseases
Discussion Leader: Hendrik van Veen (University of Cambridge, United Kingdom)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmTerence Crofts (Washington University in St. Louis, USA)
"Functional Metagenomic Discovery and Characterization of Novel Antimicrobial Resistance Mechanisms"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:25 pmJulia Oh (Jackson Laboratory for Genomic Medicine, USA)
"The Human Skin Microbiome: Metagenomics to Therapeutics"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 8:55 pmKarina Xavier (Instituto Gulbenkian de Ciencia, Portugal)
"Manipulation of the Interspecies Quorum Sensing Signal in Mouse Gut"
8:55 pm - 9:05 pmDiscussion
9:05 pm - 9:25 pmPhilip Rather (Emory University, USA)
"An RND-Type Efflux System Regulates an Epigenetic Switch Controlling Virulence in Acinetobacter baumannii"
9:25 pm - 9:30 pmDiscussion
Thursday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmPreclinical and Clinical Studies
Discussion Leaders: Deanna Kroetz (University of California, San Francisco, USA) and Victor Ling (British Columbia Cancer Research Centre, Canada)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:30 amShashank Gupta (Brown University, USA)
"Taming Tuberculosis by Efflux Inhibitors"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amErin Schuetz (St. Jude Children's Research Hospital, USA)
"P-Glycoprotein/ABCG2 Double Knockout Rat Metabolomics to Identify Novel Substrates"
10:00 am - 10:10 amDiscussion
10:10 am - 10:30 amMuriel Masi (Aix-Marseille University, France)
"Envelop Permeability and Antibiotic Accumulation in Gram-Negative Clinical Isolates"
10:30 am - 10:40 amDiscussion
10:40 am - 11:00 amCoffee Break
11:00 am - 11:20 amToshihisa Ishikawa (NGO Personalized Medicine and Healthcare, Japan)
"Challenge to Realize the Personalized Medicine and Healthcare in a Local City of Japan: From Transporter PGx Research to Clinical Application"
11:20 am - 11:30 amDiscussion
11:30 am - 11:50 amSelected from Poster Abstracts: Amro Hamdoun (University of California, San Diego, USA)
"Inhibition of P-Glycoprotein by Persistent Organic Pollutants"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:10 pmSelected from Poster Abstracts: Robert Robey (National Cancer Institute, NIH, USA)
"Zebra Fish Model for Blood-Brain Barrier"
12:10 pm - 12:15 pmDiscussion
12:15 pm - 12:25 pmSelected from Poster Abstracts: Karobi Moitra (Trinity Washington University, USA)
"Identification of Novel Variants in ABCC6 and Modifier Genes in PXE Patients by Next Generation Sequencing"
12:25 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 Technologies / Late-Breaking Topics
Discussion Leader: Jessica Blair (University of Birmingham, United Kingdom)
7:30 pm - 7:35 pmIntroduction by Discussion Leader
7:35 pm - 7:55 pmZhe-Sheng (Jason) Chen (St. John's University, USA)
"Tea Nanoparticles Potentiate the Anticancer Activity of Doxorubicin"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:20 pmSelected from Poster Abstracts: Arthur Roberts (University of Georgia, USA)
"Use of Solution NMR to Study ABC Transporter-Ligand Interactions"
8:20 pm - 8:25 pmDiscussion
8:25 pm - 8:40 pmSelected from Poster Abstracts: Valentin Rybenkov (University of Oklahoma, USA)
"Bifurcation Behavior of Drug Uptake by Gram-Negative Bacteria"
8:40 pm - 8:45 pmDiscussion
8:45 pm - 8:55 pmSelected from Poster Abstracts: Courtney Follit (Southern Methodist University, USA)
"Identification of Novel Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance"
8:55 pm - 9:00 pmDiscussion
9:00 pm - 9:10 pmSelected from Poster Abstracts: Laetitia Daury (UMR 5248, CNRS / École Nationale Supérieure de Chimie et de Physique de Bordeaux, France)
"Reconstituted Tripartite MexAB-OprM Efflux System Studied by Cryo-Electron Microscopy"
9:10 pm - 9:15 pmDiscussion
9:15 pm - 9:30 pmClosing Remarks
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture
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