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Conference Program
 
Multi-Drug Efflux Systems
Shared Molecular Mechanisms but Diverging Roles in Physiology and Medicine
March 17-22, 2013
Four Points Sheraton / Holiday Inn Express
Ventura, CA

Multi-drug efflux systems are ubiquitous in all domains of life. They are requisite in normal physiology in man, altering the pharmacology of medicines, and providing protection to the brain and other sites from toxic xenobiotics. Linked to human health, with the increasing prevalence of drug resistance in disease-causing pathogens, where efflux systems are important mediators of resistance. Multi-drug resistance in bacteria, yeast and the malarial parasite is of particular concern. Its occurrence has steadily risen in the past decades to become one of the major health concerns of our modern society. Multi-drug efflux systems present a frequently used and flexible means for eukaryotic and prokaryotic cells alike to resist our arsenal of once potent agents, gaining time to gather other mechanisms of resistance. On the other hand, the role of drug efflux and membrane transporters in human disease is also increasingly understood. Efflux transporters have been found in central roles in human disease - from drug toxicity due to interpatient variation in pharmacology-related pumps, to disease due to lack of efflux of endogenous substrates, to a potential role in cancer treatment failure or in cancer biology.

It is from the research of the many active participants of the highly appreciated and fruitful past GRCs that our knowledge on the molecular mechanisms of transport and multi-drug recognition, genetic regulation, and pharmacological modulation has gained considerable momentum. Increasingly, we understand that complex mechanisms regulate accumulation and extrusion of xenobiotics as well as therapeutic agents in eukaryotic and prokaryotic cells.

The 5th meeting on Multi-Drug Efflux Systems, will focus on the role of efflux systems in health and disease. The keynote lectures will be held by recognized leaders in the field. Sessions will be organized such that each session will be introduced by an expert scientist giving a brief overview of current knowledge relating in vitro and clinical data to particular efflux systems. We will address questions on the significance of efflux on the multidrug resistance phenotype in context of the role of uptake mechanisms, the role of efflux in eukaryotic systems, control of gene expression, and regulation on the protein level including post-translational modification. Aspects on structure and mechanism of multi-drug resistance pumps and a dedicated session on methods how to study drug transporters including imaging techniques. Concurrently, this conference will also address the multi-drug uptake systems that coexist with efflux systems in determining substrate accumulation. Sessions on the role of drug transporters in pharmacology and pharmacogenomics and on approaches to control multi-drug resistance in man and bacteria will complete the conference.

An old Japanese saying, "On Ko Chi Shin", means that we must understand the old in order to understand the new. Already the ancient organisms were equipped with multi-drug efflux systems– yet now we need to understand their structure, function, and role in the modern age. Ample time will be given for exchange of knowledge during discussions as well as opportunities for junior scientist to present their latest data. The broad yet focused range of topics will give many of us the opportunity to lay foundation for future work by including learning from the past in the ongoing quest to tackle the problem of multidrug resistance in bacterial infections and cancer.


Contributors

SUNDAY
4:00 pm - 8:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:35 pmWelcome / Introductory Comments by GRC Site Staff
7:35 pm - 7:40 pmSusan Bates and Martin Pos, Co-Chairs for Conference
"Introductory Comments and Conference Welcome"
7:40 pm - 9:30 pmKeynote Session: Importance of Multidrug Efflux Systems
7:40 pm - 7:50 pm Discussion Leader: Piet Borst (University of Amsterdam, Amsterdam, Netherlands)
7:50 pm - 8:30 pm Bob Hancock (Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada)
"Multidrug resistance and prospective solutions"
8:30 pm - 8:40 pm Discussion
8:40 pm - 9:20 pm Kathy Giacomini (University of California San Francisco, USA)
"The importance of MATE transporters as multidrug efflux pumps"
9:20 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmSignificance of Efflux Pumps in Etiology of Drug Resistance
9:00 am - 9:10 am Discussion Leaders: Paul Tulkens (Catholic University of Louvain, Brussels, Belgium) and Laura Piddock (University of Birmingham, UK)
9:10 am - 9:30 am Jean-Marie Pages (UMVF, Marseille, France)
"Clinical and in vitro data regarding efflux pump occurrence in Gram-negative bacteria"
9:30 am - 9:40 am Discussion
9:40 am - 10:00 am Keith Poole (Queens University, Kingston, Canada)
"Efflux and Antibiotic Resistance in Pseudomonas"
10:00 am - 10:10 am Discussion
10:10 am - 10:40 am Coffee Break
10:40 am - 11:00 am Brian Monk (Otago University, Dunedin, New Zealand)
"ABC Efflux pumps in Candida"
11:00 am - 11:10 am Discussion
11:10 am - 11:30 am Laura Piddock (University of Birmingham, UK)
"Regulation of multi-drug efflux pumps - identifying new targets for antibacterial drug discovery"
11:30 am - 11:40 am Discussion
11:40 am - 12:00 pm Michael Gottesman (Center for Cancer Research, National Cancer Institute, Bethesda, MD)
"Relevance of mechanisms of multidrug resistance in cultured cancer cells to clinical multidrug resistance"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Lindsey te Brake (Radboud University Nijmegen, Netherlands)
"Mycobacterium tuberculosis ABC transporter protein inhibition as a new treatment strategy against tuberculosis"
12:25 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 pmSignificance of Efflux Pumps in Health and Disease - I
7:30 pm - 7:40 pm Discussion Leader: Richard Callahan (Australian National University, Acton, AU)
7:40 pm - 8:00 pm Miguel Viveiros (Universidade Nova de Lisboa, Portugal)
"Significance of Efflux in Multidrug resistance in Mycobacterium tuberculosis"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:30 pm Paul Roepe (Georgetown University, Washington, USA)
"Multidrug transporters as mode of resistance in Malaria"
8:30 pm - 8:40 pm Discussion
8:40 pm - 9:00 pm Hermann Koepsell (University of Würzburg, Germany)
"Significance of SLC Family Proteins in Efflux in Multidrug Resistance"
9:00 pm - 9:10 pm Discussion
9:10 pm - 9:25 pm Shang Lian (St. Jude Children's Research Hospital, Memphis, USA)
"ABCC4/Mrp4 in Pediactric Acute Myeloid Leukemia (AML)"
9:25 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmStructure and Mechanism of Multi-Drug Efflux Pumps in Microbes and Man
9:00 am - 9:10 am Discussion Leader: Suresh Ambudkar (Laboratory of Cell Biology, NCI, USA)
9:10 am - 9:30 am Mike Dean (National Institute of Health, National Cancer Institute, USA)
"Comparative study of MDR transporters from the ABC and RND superfamilies"
9:30 am - 9:40 am Discussion
9:40 am - 10:00 am Markus Seeger (University of Zürich, Switzerland)
"Structure and mechanism of RND and ABC transporters: similarities and peculiarities"
10:00 am - 10:10 am Discussion
10:10 am - 10:40 am Coffee Break
10:40 am - 11:00 am Akihito Yamaguchi (Osaka University, Japan)
"Inhibitor-bound structures of a multidrug exporters AcrB and MexB "
11:00 am - 11:10 am Discussion
11:10 am - 11:30 am Shimon Schuldiner (Hebrew University, Jerusalem, Israel)
"Small but mighty: EmrE"
11:30 am - 11:40 am Discussion
11:40 am - 12:00 pm Di Xia (National Institute of Health, Bethesda, USA)
"Crystal Structure of A Multidrug ABC Transporter P-glycoprotein at 3 Å Resolution"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Chloe Martens (Free University of Brussels, Belgium)
"Deciphering the conformational dynamics of the secondary multidrug transporter LmrP using Electron Paramagnetic Resonance spectroscopy"
12:25 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 pmNew Methods to Study Membrane Transporters
Discussion Leaders: Eitan Bibi (Weizmann Institute, Rehovot, Israel) and Melissa Brown (Flinders University, Adelaide, AUS)
7:30 pm - 7:50 pm Katharine A. Henzler-Wildman (Washington University, St. Louis, USA)
"NMR spectroscopy on EmrE"
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:20 pm Helen Zgurskaya (University of Oklahoma, USA)
"The assembly and function of multidrug efflux transporters in the two-membrane envelopes of Gram-negative pathogens"
8:20 pm - 8:30 pm Discussion
8:30 pm - 8:50 pm Oliver Langer (Austrian Institute of Technology, Vienna, Austria)
"In vivo imaging of ABC transporters with positron emission tomography in epilepsy, Alzheimer's disease and cancer"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:20 pm Petra Fromme (Arizona State University, Tempe, USA)
"Avenues for structure determination of membrane proteins including femtosecond nanocrystallography"
9:20 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmRegulation and Trafficking of Membrane Transporters
9:00 am - 9:10 am Discussion Leader: Tony George (University of Technology, Sydney, AU) and Susan Michaelis (Johns Hopkins University, Baltimore, USA)
9:10 am - 9:30 am Maria Baer (School of Medicine, University of Maryland, USA)
"Expression of MDR efflux pumps in cancer: Mediators of resistance or of the malignant phenotype"
9:30 am - 9:40 am Discussion
9:40 am - 10:00 am Igor Stagljar (Department of Biochemistry, University of Toronto, Canada)
"A global analysis of the S. cerevisiae ABC transporter interaction newtork: towards a greater understanding of membrane transport"
10:00 am - 10:10 am Discussion
10:10 am - 10:40 am Coffee Break
10:40 am - 11:00 am Karl Kuchler (Christian Doppler Laboratory for Infection Biology, Vienna, Austria)
"Multidrug resistance and genetic diseases"
11:00 am - 11:10 am Discussion
11:10 am - 11:30 am Balasz Sarkadi (Hungarian Academy of Sciences, Budapest, Hungary)
"Complex regulation of ABCG2 expression and function"
11:30 am - 11:40 am Discussion
11:40 am - 12:00 pm Bob Austin (Princeton University, USA)
"The positioning logic and copy number control of genes in bacteria under stress"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Short Talk: Agnes Basseville (Center for Cancer Research, National Cancer Institute, USA)
"ABCG2 polymorphic variants of proven impact in gout and xenobiotic protection: structure and trafficking"
12:25 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 pmApproaches to Control Multidrug Resistance - in Man and Bacteria
7:30 pm - 7:40 pm Discussion Leader: Bill Shafer (Emory University School of Medicine, Georgia, USA)
7:40 pm - 8:00 pm Kim Lewis (Northeastern University, Boston, USA)
"Persistence responsible for relapsing chronic infections caused by biofilms"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:30 pm George Tegos (University of New Mexico, Albuquerque, USA)
"Efflux Inhibition: Tactics and Strategies"
8:30 pm - 8:40 pm Discussion
8:40 pm - 9:00 pm Attilio Di Pietro (Institute of Protein Biology and Chemistry, Lyon, France)
"Targeting multidrug ABC transporters in resistant cancer cells by drug-efflux inhibitors and apoptosis inducers"
9:00 pm - 9:10 pm Discussion
9:10 pm - 9:25 pm Jean-Michel Bolla (Aix-Marseille University, France)
"How to determine the mode of action of MDR blockers in bacteria?"
9:25 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmSignificance of Efflux Pumps in Health and Disease - II
9:00 am - 9:10 am Discussion Leader: Toshi Ishikawa (RIKEN Omics Science Center, JP) and Helen Zgurskaya (University of Oklahoma, Norman, USA)
9:10 am - 9:30 am Herbert Schweizer (Colorado State University, Fort Collins, USA)
"Efflux pumps in Burkholderia"
9:30 am - 9:40 am Discussion
9:40 am - 10:00 am Jürg Dreier (Basilea, Basel, Switzerland)
"Mechanism of action studies with bacterial efflux-pump inhibitors found by whole-cell screening"
10:00 am - 10:10 am Discussion
10:10 am - 10:40 am Coffee Break
10:40 am - 11:00 am Anna Siewierska (University of Lodz, Poland)
"Polymorphisms in the ABCC2 Gene and Their Influence on Melanin Synthesis Pathway - a New Approach for Understanding the Genetic Hair Color Determination"
11:00 am - 11:10 am Discussion
11:10 am - 11:30 am Hiroyuki Kusuhara (University of Tokyo, Japan)
"Identification of major substrates of efflux transporters in vivo by metabolomic analysis"
11:30 am - 11:40 am Discussion
11:40 am - 12:00 pm Annika Hartz (National Institute of Environmental Health Services, Research Triangle Park, USA)
"Role of ABC Transporters in Blood-Brain Barrier and Alzheimer's Disease"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Short Talk: Jean-Pierre Gillet (Center for Cancer Research, National Cancer Institute, Bethesda, MD)
"ABCB5: a polyspecific efflux transporter localized to the mitochondria that doubles as a melanoma tumor suppressor gene"
12:25 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 pmLatest News on Drug Efflux Pumps
7:30 pm - 7:40 pm Discussion Leader: Rik van Veen (Cambridge University, UK)
7:40 pm - 8:00 pm Jose Faraldo Gomez (Max-Planck Institute of Biophysics, Frankfurt, Germany)
"The coupling mechanism of multidrug efflux proteins"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:30 pm Satoshi Murakami (Tokyo Institute of Technology, Japan)
"Studies on beta-lactam selectivity of the multidrug transporters AcrB and AcrD"
8:30 pm - 8:40 pm Discussion
8:40 pm - 9:00 pm Olga Lomovskaya (Rempex Pharmaceuticals, San Diego, USA)
"Inhibitors of multidrug efflux pumps in bacteria: Circumventing antibacterial resistance"
9:00 pm - 9:10 pm Discussion
9:10 pm - 9:20 pm Alice Verchere (Paris Descartes University, France)
"Functional investigation of the MexA - MexB - OprM efflux pump of Pseudomonas aeruginosa"
9:20 pm - 9:25 pm Discussion
9:25 pm - 9:30 pm Concluding Remarks
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible (in part) by 1R13AI106179-01from the National Institutes of Allergy and Infectious Diseases and National Center for Advancing Translational Sciences. 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.

Last Updated: June 5, 2013
 
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