Special Research Program 35 (SFB 35)
"Transmembrane Transporters in Health and Disease"
The SFB 35 project was funded by the FWF from
February 01, 2008 - September 30, 2018.
Speaker of SFB35: Prof. Dr. Harald H. Sitte
Deputy Speaker of SFB35: Prof. Dr. Michael Freissmuth
Seminar series "Colloquia in membrane transport"
General information
Transporters play a pivotal role in the translocation of molecules across biological membranes. Almost 400 different families of transport systems exist, which determine the fate of a plethora of different substrates. Accordingly, transporters regulate essentially all fundamental biological processes, including metabolism and energy supply, cytoplasmic concentrations of physiologically important ions, signal transduction and defense against potentially toxic agents. Transporter biology has attracted a steadily increasing interest and it is among the most rapidly growing fields. There are several reasons for this surge in popularity, not the least of which are that insights are of clinical relevance and that increased mechanistic understanding translates into therapeutic benefit (e.g. selective antidepressant drugs, psychostimulant therapy of attention-deficit hyperactivity disorder (ADHD), resistance to chemotherapy, drug-resistant epilepsy and many more).
This consortium focuses on two medically relevant transport systems, neurotransmitter transporters and ABC-transporters and proposes to address three areas of enquiry:
- study the structure-function relationship of these transporters and bacterial homologues thereof (suitable for structural approaches) by employing computational approaches (QSAR and pharmacophore modelling, computational structural biology), biochemical and biophysical techniques including atomic force microscopy, crystallography, electrophysiology, fluorescence correlation spectroscopy and related techniques.
- analyse by using cell biology, biochemistry and mouse genetics how expression of transporters is regulated by physiological stimuli, by the action of pharmacochaperones and by regulated export from the ER
- translate these insights into clinical paradigms by developing PET-ligands to study drug-resistant epilepsy by correlating clinical data with transporter expression (NaPi-, serotonin-, dopamine transporters, P-glycoprotein) to understand the pathophysiology of variations in transporter expression and function; identify genetic polymorphisms accounting for phenotypic differences in drug response and disease susceptibility.
The current consortium has been assembled under the assumption that there are several Austrian research groups whose interests are aligned under this common theme. We anticipate that this consortium has both, a critical mass and a unique combination of conceptual and technical know-how, to occupy a unique position, because we cover the range from bacteria to man, from structural analysis to understanding complex disease entities, from visualizing single molecules to functional imaging of transporters in the most complex tissue, the living brain. We thus bridge the gap between basic biology and clinical medicine. It is evident that the flow of information is not unidirectional in this consortium; disease-susceptibility or drug resistance may result from transporter gene polymorphisms and these may be identified in selected patients. Mechanistic insights on the effect of the mutation, however, require an understanding on how this alteration affects transporter structure, function and surface expression.
Members
Alphabetical listing of all participating researchers:
Univ.-Prof. DI Dr. Christoph Baumgartner, 2008 – 2012 (to project)
2nd Neurological Department, General Hospital Hietzing with Neurological Center Rosenhügel,
Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology
christoph.baumgartner@wienkav.at
Univ.-Prof. Dr. med. Peter Chiba, 2008 – 2018 (to project)
Institute of Medical Chemistry Medical University of Vienna
peter.chiba@meduniwien.ac.at
Univ.-Prof. Dr. Gerhard F. Ecker, 2008 – 2018 (to project)
University of Vienna Dept. of Pharm. Chemistry
Pharmacoinformatics Research Group
gerhard.f.ecker@univie.ac.at
Univ.-Prof. Dr. med. Michael Freissmuth, 2008 – 2018 (to project)
Deputy Speaker of SFB35 Institute of Pharmacology
Medical University of Vienna
michael.freissmuth@meduniwien.ac.at
Univ.-Prof. DI Dr. Peter Hinterdorfer, 2008 – 2018 (to project)
Institute of Biophysics Johannes Kepler University Linz
peter.hinterdorfer@jku.at
Univ.-Prof. Dr. Karl Kuchler, 2008 – 2018 (to projects)
Center for Medical Biochemistry
Max F. Perutz Laboratories
Medical University of Vienna
karl.kuchler@medukniwien.ac.at
Univ.-Prof. Dr. med. Markus Müller, 2008 – 2015 (to project)
Department of Clinical Pharmacology
Medical University of Vienna
markus.mueller@meduniwien.ac.at
Ass. Prof. Dr. Gaia Novarino, 2015 – 2018 (to project)
Institute of Science and Technology (IST)Klosterneuburg
gaia.novarino@ist.ac.at
Assoc. Prof. Priv. Doz. Dr. med. Univ. Lukas Pezawas, 2008 – 2012 (to project)
Department of Psychiatry and Psychotherapy
Medical University of Vienna
lukas.pezawas@meduniwien.ac.at
Univ.-Prof. Dr. med. Daniela Pollak, 2012 – 2015 (to project)
Department of Neurophysiology and Neuropharmacology
Medical University of Vienna
daniela.pollak@meduniwien.ac.at
Univ.-Prof. Dipl.-Ing. Dr. Gerhard J. Schuetz, 2012 – 2018 (to project)
Institute of Applied Physics TU Vienna
schuetz@iap.tuwien.ac.at
Univ.-Prof. Mag. Dr. Maria Sibilia, 2012 – 2017 (to project)
Institute of Cancer Research Medical University of Vienna
maria.sibilia@meduniwien.ac.at
Univ.-Prof. Dr. med. Harald H. Sitte, 2008 – 2018 (to project)
Speaker of the SFB35 Institute of Pharmacology
Medical University of Vienna
harald.sitte@meduniwien.ac.at
Ass. Prof. Dr. Thomas Stockner, 2015 – 2018 (to project)
Institute of Pharmacology Medical University of Vienna
thomas.stockner@meduniwien.ac.at
Dr. Peggy Stolt-Bergner, 2008 – 2012 (to project)
IMP – Research Institute of Molecular Pathology Vienna
stolt@imp.ac.at
Univ.Prof. Dr. med. Gergely Szakács, 2015 – 2018 (to project)
Institute of Cancer Research
Medical University of Vienna
gergely.szakacs@meduniwien.ac.at
Univ.-Prof. Dr. Michael Trauner, 2012 – 2018 (to project)
Hans Popper Laboratory of Molecular Hepatology
Division of Gastroenterology and Hepatology
Department of Internal Medicine III
Medical University of Vienna
michael.trauner@meduniwien.ac.at
Projects
Membrane transporters in drug refractory epilepsy
Christoph Baumgartner
Epilepsy is a chronic neurological disorder that affects 0.5 to 1% of the population. 30 to 40% of patients are medically refractory to antiepileptic drugs and thus represent a major health care problem. According to the World Health Organization, disability due to epilepsy accounts for approximately 1% of the global burden of disease, which ranks epilepsy just after major affective disorders, dementias, and alcohol dependence among primary disorders of the nervous system, and comparable to the worldwide burden due to breast and lung cancer. Thus, research on the mechanisms underlying medically refractory epilepsy is one of the hot topics in epilepsy research. One promising hypothesis has been the so-called transport hypothesis which states that multidrug transporters are over-expressed in the seizure focus of patients with medically refractory seizures. This hypothesis is supported by the results of clinical and genetic studies in humans as well as by animal research. Human epilepsy offers the unique opportunity to investigate human brain tissue which has been removed during epilepsy surgery in vitro and therefore to elucidate further the mechanisms underlying medically refractory epilepsy.
Interaction of TMTs with low molecular weight ligands
Peter Chiba
Pharmacotherapy of human diseases relies on the ability of drugs to specifically interact with macromolecular target structures. The majority of drugs in the market are small molecules, which in more than half of all cases target membrane proteins. The latter frequently function as receptors, ion channels or transmembrane transporters. The overall aim of this project part is an improved understanding of the interaction of drugs and drug-like molecules with prototypic ABC-transporters. This is important for three reasons: (i) those members of the human ABC family, which are involved in drug transport, play a key role for pharmacokinetics of systemically administered drugs; (ii) malfunction of ABC proteins is causally related to more than 25 human disease entities and examples of successful pharmacotherapy with small molecules have been established; (iii) several systemically administered drugs interfere with the function of the human bile salt export pump, a subfamily B ABC transporter, which results in adverse and sometimes life threatening drug side effects. Our experiments focus on two members of the human ABC protein family, the multidrug transporter P-glycoprotein (ABCB1) and the bile salt transporter BSEP (ABCB11). Our studies promote a conceptual understanding of how drugs and drug-like molecules interact with ABC transporters of the ABCB subfamily and how protein domains communicate to bring about cargo transport. They also identified chemical starting points for small molecule correctors of mutation induced misfolding of model ABC transporters.
Molecular basis of drug-transporter interaction
Gerhard F. Ecker
The overall objective of the project was to explore the interaction of small molecules with transmembrane transporters on the molecular level using a panel of computational methods. Subsequently, utilising the broad experimental expertise in the consortium, the models should be validated and refined. In particular, we aimed at (i) creating a set of protein homology models of selected ABC- and SLC-transporter and use these models for docking of small molecules, (ii) use the validated models for in silico screening and identification of new ligands, (iii) develop large scale classification models for transporter ligands, (iv) link predicted transporter interaction profiles to in vivo effects, and (v) establish sustainable web-platforms for models and data.
In line with these aims, we developed an experimental data guided docking protocol, which allowed to postulate and validate binding modes of propafenones and analogs in P-glycoprotein, tricyclic antidepressants in SERT, cathinones in SERT and DAT, and tiagabine in GAT1. The latter served also as template for a structure-based pharmacophore model, which allowed to identify liothyronine as GAT1 inhibitor. Furthermore, exploiting the validated docking protocol enabled us to develop – for the first time – large scale structure-based classification models for P-gp, BSEP, and BCRP. These models were complemented by ligand-based machine learning classification models for inhibitors and substrates of P-gp, BSEP, BCRP, MRP2, MRP3, and MRP4. In light of aim (v), these models were implemented in a web-platform, which is free for academic use (http://livertox.univie.ac.at). The models served also for our attempts to translate predicted transporter interaction profiles to in vivo hepatotoxicity, such as hyperbilirubinemia, cholestasis, and drug induced liver injury. An analogous approach allowed to link cns-transporter and receptor profiles to side effects of a panel of antidepressant drugs. Finally, we gained first evidence, that the concept of drug residence time might also be applicable in the field of transmembrane transporter.
ER export of neurotransmitter transporters
Michael Freissmuth
The original proposal focused on the C-terminus of SLC-family members. The working hypothesis postulated that (i) the recruitment of SEC24 to the C-terminus was not only required for ER export but also specified axonal targeting; (ii) that – because of its divergent C-terminus – SERT (= the serotonin transporter) differed from its close relatives (DAT = the dopamine transporter, NET = the norepinephrine transporter, GAT1 = the GABA-transporter-1) by requiring a SEC24-isoform for export from the endoplasmic reticulum (ER) other than SEC24D; (iii) that the C-terminus of SERT was required for folding of the transporter. Over the three funding periods we confirmed several of these conjectures. Based on our observations, we developed a chaperone COPII-exchange model. This model posits that the folding trajectory of SERT is monitored by a heat-shock protein relay. Recruitment of the COPII machinery is contingent on prior release of the heat-shock proteins, because the binding sites for the cognate SEC24-isoform and the heat-shock protein overlap. This precludes premature export of partially folded transporter molecules. This model has both, explanatory and predictive power and provides a framework to develop pharmacochaperones suitable to rescue folding deficient mutants. The model can, for instance, explain why the folding deficiency can be transmitted as both, a recessive and an autosomal dominant trait. The model also predicts that HSP-inhibitors rescue cell surface expression and function of mutant transporters, a prediction, which was verified in flies. Our collaborative work within the consortium has shed light on oligomeric assembly, on the conformational changes in the N-terminus, on the binding mode of ligands etc. and thereby also informed our search for additional pharmacochaperones.
Single molecular forces in recognition and transport of TMTs
Peter Hinterdorfer
The major part of our studies was focused on mapping the molecular interaction energy landscapes involved in ligand (citalopram, MFZ2-12, MDMA, dopamine) recognition and probing the conformational transport cycle during ligand binding to the serotonin transporter (SERT). We thus studied the interaction forces that occur during transport cycles of a series of substrates and inhibitors with SERT and dopamine transporter (DAT) wild types and selected mutants in cellular membranes. To attach the ligands to AFM tips, different crosslinking methods were elaborated. Force spectroscopy (FS) studies demonstrated that there are two allosterically coupled binding sites in SERT for citalopram (Zhu R et al., Angewandte Chemie International Edition, 2016) This finding was subsequently confirmed by X-ray structure studies (Coleman JA et al., Nature 2016). Two binding sites in DAT were also revealed by using AFM tips functionalized with MFZ2-12 or dopamine. The FS results show that MDMA can interact with both SERT and DAT as well as with cell membrane not expressing these transporters, thus indicating that MDMA can enter the cell either through the transporters or via direct diffusion across the plasma membrane (Sandtner W et al., British Journal of Pharmacology, 2014; Crowe A et al., European Journal of Pharmacology, 2008). Force data collected on SERT with bi- and tetra-valent crosslinkers carrying citalopram and MFZ2-12 showed both simultaneous and sequential ruptures of multi-valent bindings, indicating that SERT organizes in oligomers in the plasma membrane. This was further supported by TREC data revealing DAT and SERT nanodomains (~ 10 to 100 nm in diameter) in the cell membrane. In an additional study, we aimed to evaluate the binding mechanism of ABCB1 transporter (P-glycoprotein, P-gp) with a propafenone analogue. Two different disc-forming techniques, namely styrene maleic acid lipid particles (SMALPs) and nanodiscs (NDs) were used to reconstitute P-gp in its active form and an alkyne-functionalized propafenone derivative was bound onto AFM tips via a poly ethylene glycol (PEG) linker. Both SMALPs and nanodiscs represent attractive systems for studying P-gp because they are simple, controlled nano-environments in which P-gp is reconstituted in its active form. Overall, our studies emphasize the potential of single molecule force spectroscopy and recognition imaging for the investigation of structure and function of transmembrane transporters at the single molecule level in cell membranes and model nano-systems (SMALPs and nanodiscs).
The molecular mechanism of drug transport mediated by fungal ABC transporter
Karl Kuchler
The subproject dissected the molecular mechanisms of drug transport mediated by yeast ABC transporters, to better understand the molecular basis of multidrug resistance development and drug substrate specificity of eukaryotic ABC transporters. ATP-binding cassette (ABC) proteins form one of the largest protein families with several 1000 genes operating in all living cells from bacteria to yeast, as well as man. Notably, eukaryotic ABC transporters mediate anticancer resistance, limit efficacies of anti-infective therapies, and several human genes are implicated in prominent genetic diseases. Although the domain organization of ABC proteins is conserved in evolution, the molecular mechanism of function has remained an unsolved mystery. We even have a limited molecular understanding of their transport mechanisms, which is, however, a mandatory prerequisite to combat drug resistance phenomena. Hence, the aim of subproject F3504 was to dissect the molecular mechanisms of ABC transporters from the fungal pleiotropic drug resistance (PDR) family, to decipher the molecular basis of drug substrate specificity. Thus, we delineated possible mechanisms of fungal PDR transporters, and analyzed their expression regulation under normal growth and in response to adverse conditions. We combined molecular-genetic structure-function analysis with approaches such as biochemical purification, mutagenesis and functional reconstitution. We also studied the intracellular trafficking and targeting of some PDR transporters. Finally, the coordinates of high resolution ABC protein structures, and elaborate homology comparisons with eukaryotic ABCs, enabled us to generate a structural model of the prototypic Pdr5 efflux pump, including the experimental validation of model predictions.
Molecular structure-function analysis of eukaryotic ABC Transporters
Karl Kuchler
The main aim of the final phase of SFB3520 was to delineate the mechanism of the mammalian ABCG2 transporter in drug efflux. Based on our validated structural homology models for yeast PDR transporters, we propose a mechanism whereby the transmission interface connects the force from the catalytic cycle with the membrane regions for substrate translocation. The PDR model facilitated a first version of a new ABCG2 homology model, which will be extensively scrutinized, refined and validated in phase 3, which will focus our work on advancing our understanding of mammalian ABCG family transporters. First, we will validate the new ABCG2 homology model by extensive site-directed mutagenesis and expression in a polarized cell system established in phase 2. The transfected polarized system is also suitable to study inhibition / docking for ABCB/ABCG transporters using novel corrector / inhibitor compounds, as well as to study ABCG2 assembly, dimerization, folding and intracellular targeting. Further, we will address (i) how model-based mutations control NBD dimerization or domain interactions in ABCG2, (ii) how mutations alter the transmission interface interaction with membrane regions and impact susceptibility to pharmaco-chaperones. Furthermore, we wish to answer two additional major questions concerning ABCG2 function. First, how is ABCG2 assembled and delivered to membranes. Second, how is the function of ABCG2 regulated at the transcriptional and post-translational levels. Finally, we will attempt to establish the membrane two-hybrid interaction system MaMTH and the proteomics-based M-Track protein interaction system to identify novel interaction partners controlling ABCG2 function. We expect that our strategies will contribute to a better understanding of the transport mechanisms shared by two evolutionary conserved orthologous families, the eukaryotic PDR and ABCG2 transporter families in fungi and mammalian cells, respectively.
Imaging the distribution of cerebral multidrug transporters in epilepsy patients with PET
Markus Müller
Adenosine triphosphate-binding cassette (ABC) transporters expressed in the luminal membrane of brain capillary endothelial cells, such as P-glycoprotein (Pgp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), restrict brain distribution of many drugs. A seizure-induced up-regulation of ABCB1 at the BBB is discussed as a factor contributing to drug resistance in epilepsy. Positron emission tomography (PET) imaging with suitable radiotracers offers the perspective to non-invasively study transporter function and expression in vivo in order to elucidate the role of ABC transporters in the pathogenesis of neurological disease. In the present project we developed novel PET protocols to measure ABCB1 and ABCG2 function at the BBB and successfully applied these protocols to study transporter function in animal models as well as in human patients.
LAT1 transporter in autism spectrum disorders
Gaia Novarino
Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.
Multimodal Imaging of human Brain Monamine Transporters
Lukas Pezawas
Over the last three years we have been able to establish an Imaging Genetics database of 150 remitted Major Depressive Disorder (MDD) patients and 150 healthy subjects, which comprises extensive clinical and psychometric information, DNA, functional as well as structural MRI data, and is in place now since June 2011. All genotypes of interest within this study have been associated with MDD and are related to the monoamine, neurotrophin, stress, and glutamate system. Most genetic variants have already been genotyped and all will be by the end of this year. Since Imaging Genetics studies require large sample sizes to study subtle effects and further challenge analysts in the context of data processing, we have successfully succeeded to develop several techniques in order to provide a fast data processing pipeline as well as to implement sophisticated methods that enable us to study neuronal effects on a brain systems level. Because the collection of such a large data set is time consuming, we focused within this funding period predominantly on neuroscientific questions requiring smaller sample sizes. We have achieved one of our major goals that are to relate platelet 5-HT uptake to neural functionality of emotion brain regions, which is a novel approach and demonstrates the feasibility to utilize peripheral biomarkers as predictors of neural function. Secondly, we have addressed an unresolved clinical question, namely, how the brain is able to maintain remission after successful antidepressive therapy. We have been able to demonstrate that emotion brain centers exhibit an active counter-regulation in order to maintain remission. Furthermore, we have been interested in the level of cognitive functioning of remitted MDD patients, which has turned out to be affected by this illness. Similarly, we have been interested, which medial prefrontal brain region is orchestrating the interplay between emotion and cognition domains, which are both affected in MDD patients. These purely clinical questions are currently under investigation with regard to their genetic regulation by genes affecting the monoaminergic system. Additionally, we recently started the exploitation of our imaging genetics database putting specific emphasis on epistasis between monoaminergic genotypes and gene candidates related to MDD in order to facilitate the understanding of the complex neurobiology of MDD. Finally, we initiated several side-projects such as a pharmacogenetic project that is capable to relate antidepressant side effects to specific receptor systems providing information on drug targets that increase risk for or protection against side effects. Moreover, we are currently waiting for the results of a biomarker analysis of our database that will enable us to relate potential diagnostic biomarkers for MDD to neural activity thereby providing further evidence of their specificity.
Neurotransmitter transporters in mouse models of psychiatric disorders
Daniela Pollak
The overall aim of the project as described in the application in 2011 was to link environmental depressiogenic conditions to alterations in SERT levels and function and to define some of the molecular elements mediating their impact on depression-like behavior. Using the maternal immune activation model (MIA), we identified alterations in hippocampal SERT levels resulting from early life stress, which are associated with depression-like behavior. An involvement of chromatin remodeling process as potential underlying molecular mechanism is suggested. Given the relevance of IL-6 for mediating the effects of MIA on depression-like behavior we went on to further characterize a potential direct regulation of SERT function and depression-like behavior by IL-6 (with Freissmuth). We were able to demonstrate that IL6 directly controls SERT levels and consequently serotonin reuptake through the canonical IL6 -receptor-dependent signaling pathway leading to an increased association of phosphorylated STAT3 with the SLC6A4/SERT promoter. Aiming to further elucidate the intracellular signaling pathway through which STAT3 mediates the IL-6 induced effect on SERT transcription, we examined the relevance of plasma membrane rafts for IL-6 dependent STAT signaling. Here, we obtained preliminary evidence for a direct interaction between SERT and the lipid raft protein Flotillin-1. We further confirmed this initial finding by several independent methods and continued to examine the functional relevance of the physical interaction between Flotillin-1 and SERT both in-vitro and in-vivo using Flotillin-1 knock-out mice (with Sitte).
Supermolecular organization of transmembrane transporter
Gerhard J. Schütz
We explored the nanoscopic organization of serotonin transporter (SERT) in the live cell plasma membrane using advanced single molecule microscopy tools, in close collaboration with Sitte, Freissmuth, and Stockner. Based on previous FRET experiments from the Sitte lab, we expected homo-oligomerization of SERT, however, stoichiometry, distribution of oligomeric states, interaction kinetics, and protein mobility was unknown. Using single molecule approach, we could extract this information. We observed that a broad distribution of stoichiometry of SERT exists in transfected CHO or HEK cells, ranging from monomers (~35%) up to pentamers (~10%), but no clear preference for one particular state. Our data agrees with a linear aggregation model, in which the addition of every new SERT subunit to an existing complex follows identical binding kinetics (Anderluh et al., J Biol Chem 2014). We further applied a new single molecule microscopy modality developed in our lab, which allowed us to monitor the integration rate of photobleached SERT monomers into SERT oligomers directly in the live cell plasma membrane. Within a minute’s time window, no such integration was observed (Anderluh et al., J Biol Chem 2014). We found no correlation between cluster stoichiometry and surface density of SERT, indicating that the oligomeric state is adjusted in subcellular organelles prior to SERT transport to the plasma membrane (Anderluh et al., J Biol Chem 2014); at the plasma membrane, SERT oligomers are kinetically trapped. We used single molecule tracking to determine SERT mobility and found that the mobility is high both at the plasma membrane and at the endoplasmic reticulum (ER) (Anderluh et al., Biophys. J. 2014). We found that SERT oligomer assembly at the ER membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization. After trafficking to the plasma membrane, however, the SERT stoichiometry is fixed. Stabilization of the oligomeric SERT complexes is mediated by the direct binding to phosphoinositide phosphatidylinositol-4,5-biphosphate (PIP2). (Anderluh et al., Nat Commun. 2017). Also, we used single molecule methods to obtain the mobility, interaction kinetics and oligomerization state of dopamine transporter (DAT). Our results suggest that the oligomerization of DAT is different from that of SERT. DAT shows a major dimeric fraction as opposed to multimers (up to pentamers) as seen with SERT. We are now investigating the factors, which modulate the oligomerization behavior of DAT. Additionally; we are probing the spatial organization of SERT in its native form in the axonal plasma membrane of serotonergic neurons.
EGFR-mediated regulation of transmembrane transporters
Maria Sibilia
Loss of EGFR in murine brains results in a neurodegenerative phenotype in the neocortex with defective astrocytes while the midbrain astrocytes are normal. In addition, EGFR deficient mice are more susceptible to kainic acid (KA)-induced epileptic seizures. We identified that the two major astroglial glutamate transporters GLAST and Glt1 are downregulated in EGFR deficient cortical astrocytes but not midbrain astrocytes. Together with the group of Sitte we could demonstrate that the uptake of glutamate is indeed impaired in cortical but not in midbrain astrocytes. Moreover, injection of Glut-R antagonists into newborn EGFR knock-out mice are able to delay the development of neurodegeneration suggesting that impaired glutamate transporter expression and glutamate uptake might be at the basis of the observed neurodegeneration and KA sensitivity. We have also found that EGFR signalling regulates the expression of the ABC transporters ABCG2 and ABCB1 in the liver. This occurred not only in hepatocytes but also in myeloid cells. Together with the group of Trauner and Langer (cooperation partner and former SFB member) we investigated whether the aberrant expression of these ABC transporters in mice lacking the EGFR in various liver cells affected the development of inflammatory liver diseases and cancer. We found that the EGFR protects hepatocytes from DEN-induced damage. Surprisingly, we discovered that EGFR plays a tumor-promoting function in Kupffer cells/liver macrophages and not as anticipated in tumor cells. Expression analysis of all ABC transporters in hepatocytes and Kupffer cells revealed that ABCG2 protein levels were lower in mice lacking EGFR in hepatocytes, whereas the cholesterol transporters ABCA1, A9 and D2 were downregulated in Kupffer cells. However, feeding Western diet to mice lacking the EGFR in myeloid cells did not reveal any differences in atherosclerosis development compared to wild-type controls. Moreover, in vivo imaging studies (MR imaging, PET Scan analysis) demonstrated that the biliary efflux clearance of Erlotinib, a substrate for both ABCB1 and ABCG2 in HCC, is reduced in EGFR deficient livers providing the first demonstration that EGFR signaling can regulate in vivo ABCG2 transport activity in the liver. These findings suggest that EGFR deficient livers are more sensitive to chemotherapy and thus anti-cancer drugs, which are substrates of ABC.
Structure/function relationships of bacterial and human transporter orthologues
Harald H. Sitte
In aim 1, we explored bacterial orthologues of SERT and DAT in a comparative approach. During the entire funding period, we established the purification and reconstitution of LeuTAa and assessed conformational equilibria in detergent micelles and proteoliposomes using the Lanthanide resonance energy transfer technique (with Stolt-Bergner, Freissmuth and Stockner). We resolved a discrepancy between the published crystallized structures in micellar environment and membrane-embedded LeuTAa. Furthermore, we developed several homology models various SLC6 members (with Ecker, Freissmuth and Stockner). In aim 2, we explored the nature of the conducting state in SERT by applying electrophysiological and fluorescence spectroscopical techniques; we explored the conformational cycling of SERT in detail and examined the ionic dependence of transported substrates (with Freissmuth). We tested several psychostimulant drugs and defined their mode of action: In detail, we defined the fine line between compounds acting as substrates which are able to elicit reverse transport and compounds behaving as inhibitors (with Ecker, Freissmuth). Together with Ecker and Schütz, we examined the structural importance of phosphoinositides (PIP2) on the function and quaternary arrangement of SERT. Furthermore, we examined the phosphorylation status of DAT and SERT and assessed the influence of αCamKII on amphetamine effects (with Freissmuth, Pollak). In aim 3, we used a number of different psychostimulant drugs, such as various methcathinone and amphetamine derivatives, which serve to assess the specificity of NSS members (with Ecker, Freissmuth, Stockner).
Free energy profile of membrane transporter
Thomas Stockner
The mechanism of transport can be predicted from simulations at the atomic level, if all relevant conformations can be sampled properly. This was possible by identifying the low energy paths and quantifying the associated energies. Therefore, biochemical experiments were combined with advanced simulations methods, using steered molecular dynamics simulations, potential of mean force calculations, metadynamics and enforced rotations in all aims to obtain, and importantly, to verify the results. In the focus of this project part were the prototypic members of the SLC6 and ABC transporter families: SERT, ABCB1 and ABCB11. The main goal of aim 1 and 2 was to investigate underlying principles, which allow for the discrimination between substrates and inhibitors by SERT. The series of methylene-dioxy-methamphetamine compounds (including 'ecstasy') changed from substrate to inhibitor as the number of methyl-substitutions at the nitrogen atom increased. By a combination of biochemical experiments with advanced simulations methods were molecular size and especially the electrostatic properties (surface potential and dipole moment) of the substrate identified as the dominant interactions responsible for the change in behaviour. The transport cycle of ABC exporters was the focus of aim 3 and 4. Combining experiments with advanced simulation techniques and comparing ABCB1 with ABCB11 allowed for characterization of the common denominator and also the differences of canonical versus degenerate ATP binding site. Free energy calculations of isolated nucleotide binding domains allowed for quantification of forces, conformation, interactions and energies through which ABC transporters harvest the energy of ATP and use it for directional substrate transport.
Selection of Stable Transporters to Facilitate their Structural Characterisation
Peggy Stolt-Bergner
Crystallization of integral membrane proteins is difficult due to their instability when outside of the native membrane environment. One approach to facilitate the crystallization of membrane proteins for structure determination is to utilize more stable forms of the protein of interest, an approach that has led to several new crystal structures of membrane proteins (Abramson et al., Science. 2003; Warne et al., Nature. 2008; Standfuss et al., J Mol Biol, 2007). However, no high-throughput and generally applicable method for identifying stabilizing mutations has yet been developed.
We have chosen the peptide transporter (PTR) family as a model system to develop techniques for identification of thermostable transporter mutants. Unlike many other transporter families, which have very specific substrates, PTRs transport a wide array of di- or tri-peptides and peptidomimetics. Therefore, the human orthologues of this family play an important role in drug metabolism. We are interested in structural and functional characterization of this family, to learn more about these proteins’ substrate specificity and mechanism of transport, as well as transport mechanisms in general.
Structure-function studies of ABCB6 and ABCB1
Gergely Szakács
The purpose of this project part was to elucidate the molecular mechanism of ABCB1 and the intracellular trafficking of ABCB6. The interest in these two transporters stems from their involvement in multidrug resistance of cancer and a hereditary disease affecting pigmentation, respectively. During the reporting period, we have established a comprehensive experimental system to characterize the catalytic and transport activity of ABCB1, and established methods to concomitantly monitor drug binding and conformational changes. By measuring drug binding affinity and conformational flexibility in live cells we have shown that nucleotide binding drives Pgp from a high to a low substrate-affinity state and this switch coincides with the flip from the inward-to the outward-facing conformation. We found that the catalytically inactive double Walker A mutant is stabilized in a high substrate affinity inward-open conformation, but mutants with one intact catalytic center preserve their ability to hydrolyze ATP and to promote drug transport, suggesting that the two catalytic sites are randomly recruited for ATP hydrolysis. The intracellular localization of ABCB6 has been a matter of debate, as it has been suggested to reside in the mitochondria and the endo-lysosomal system. Using a variety of imaging modalities, including confocal microscopy and EM, we confirmed the endo-lysosomal localization of ABCB6 and showed that the protein is internalized from the plasma membrane through endocytosis, to be distributed to multivesicular bodies and lysosomes. We found that the folding, dimerization, membrane insertion and ATP binding/hydrolysis of the core–ABCB6 complex devoid of the N-terminal transmembrane domain (TMD0) are preserved. Collectively, our results reveal that TMD0 represents an independently folding unit, which is dispensable for catalysis, but has a crucial role in the lysosomal targeting of ABCB6.
Molecular regulation of hepatobiliary ABC transporters in cholestatic liver diseases
Michael Trauner
Within the SFB35 we investigated the key role of canalicular ABC transporters for cholestatic liver and downstream bile duct injury. We could show that genetic modulation of ABCB11 (major determinant of bile acid (BA) excretion), protected from acquired cholestatic liver and bile duct injury. In line, double knock out mice lacking both ABCB4 (model of sclerosing cholangitis) and ABCB11 were protected from BA induced cholestatic liver injury. However, mice lacking ABCB4 and the BA receptor FXR (which also have reduced ABCB11 expression) were protected from BA-induced bile duct injury while showing aggravation of hepatocellular injury. Notably absence or pharmacological inhibition of ABCB1 and ABCG2 in mice had no impact on BA excretion and cholestatic liver injury. Using 18[F]ciprofloxacin as PET tracer in ABCB4 KO mice we characterized the impact of norUDCA (a drug in phase III clinical trial for PSC) on ABC transporter function by demonstrating reduced hepatic tracer retention which correlated with induction of basolateral ABC transporters. These finding may indicate that PET tracer studies may help to functionally visualize/assess the therapeutic adaptive basolateral ABC transporter response in cholestasis. Furthermore, in vitro we identified the thyroid hormone receptor (THR) ligand triiodothyronine (T3) as important modulator of ABCB4 gene expression potentially protecting against BA toxicity.
SFB35 Symposia
In nearly eleven years of being conducted, the Annual SFB35 Symposium welcomed almost 1.600 participants from 33 countries all over the world. Interestingly, participation from our neighbouring countries Germany and Hungary was the strongest, but we also attracted participation from Chile, India, Australia, Japan and Canada. Other frequent nationalities to be seen at the symposium are American and Danish, apart from the obvious most frequent Austrian nationality.
Symposium 2018 "The Transporter Transition"
Jenny Aguilar, USA
Susan G. Amara, USA
Ivet Bahar, USA
Selva Baltan, USA
Andre Bazzone, Germany
Shreyas Bhat, Austria
Laura Bianchi, USA
Elizabeth Bilsland, Brazil
Irina Borodina, Denmark
Olga Boudker, USA
Roch-Philippe Charles, Switzerland
Roberta de Ceglia, Switzerland
Eric Delpire, USA
Mauricio Di Fulvio, USA
David Dickens, United Kingdom
Daniela Digles, Austria
Katharina Duerr, United Kingdom
Tanja Dujic, Bosnia and Herzegovina
Lena Eliasson, Sweden
Rita Fagan, USA
Louise Fets, United Kingdom
Ulrik Gether, Denmark
Freja Herborg, Denmark
Scott Jackson, Switzerland
Thomas Jentsch, Germany
Baruch Kanner, Israel
Douglas Kell, United Kingdom
Habibeh Khoshbouei, USA
David Krantz, USA
Daniel Lackner, Austria
Kenneth Lindegaard Madsen, Denmark
Claus Loland, Denmark
Cristina Manatschal, Switzerland
Felix Mayer, USA
Laura F. McNair, Denmark
Ahmad Reza Mehdipour, Germany
Haley Melikian, USA
Satoshi Murakami, Japan
Caroline Neumann, Denmark
Anne Nies, Germany
Bala Krishna Prabhala, Denmark
Manuele Rebsamen, Austria
Nicolas Reyes, France
Claudio Rivera, Finnland
Paul Rosenberg, USA
Renae Ryan, Australia
Lei Shi, USA
Claire Steppan, USA
Sonja Sucic, Austria
Giulio Superti-Furga, Austria
Dániel Szöllősi, Austria
Mladen Tzvetkov, Germany
Suzanne Underhill, USA
Don Van Meyel, Canada
Alyssa West, USA
Yun Zhou, Norway
Christine Ziegler, Germany
Symposium 2017
Speakers:
Walter Berger, Austria
Joseph Bryan, USA
Paul Gasser, USA
Ulrik Gether, Denmark
Joachim Geyer, Germany
L. Keith Henry, USA
Peter Hinterdorfer, Austria
Saul Karpen, USA
Oliver Langer, Austria
Paul Lockman, USA
Hassane S. Mchaourab, USA
Joseph Mindell, USA
Sven Rottenberg, Switzerland
Gary Rudnick, USA
Renae Ryan, Australia
Balázs Sarkadi, Hungary
Lutz Schmitt, Germany
Gerhard Schütz, Austria
Satinder K. Singh, USA
Bruno Stieger, Switzerland
Sonja Sucic, Austria
Giulio Superti-Furga, Austria
Stina Syvänen, Sweden
Gergely Szakacs, Austria
Robert Tampé, Germany
Michael Trauner, Austria
Andras Varadi, Hungary
Matthäus Willeit, Austria
Short talks - Poster Award Winners:
Eric R. Geertsma (Goethe University Frankfurt, Germany)
Javier Koh (Duke NUS Medical School, Singapore)
Lisa Konrad (University of Copenhagen, Denmark)
Julia Preobraschenski (Max Planck Institute for Biophysical Chemistry, Germany)
Alice Verchere (Weill Cornell Medicine, USA)
Symposium 2016
Speakers:
Randy Blakely, USA
Piet Borst, The Netherlands
Olga Boudker, USA
Ellen Closs, Germany
Gerhard Ecker, Austria
Michael Freissmuth, Austria
Bruno Giros, Canada
Michael Gottesman, USA
Peter Hasenhütl, Austria
Baruch Kanner, Israel
Karl Kuchler, Austria
Claus Loland, Denmark
Hartmut Luecke, USA
Haley Melikian, USA
Gary W. Miller, USA
Amy Newman, USA
Poul Nissen, Denmark
Gaia Novarino, Austria
Manuel Palacin, Spain
Christian Pifl, Austria
Harald Sitte, Austria
Dirk Slotboom, The Netherlands
Thomas Stockner, Austria
Kristian Strømgaard, Denmark
Kazumitsu Ueda, Japan
Robert Vandenberg, Australia
Roxanne Vaughan, USA
Francois Verrey, Switzerland
Harel Weinstein, USA
Mark H. Wightman, USA
Symposium 2015
Speakers:
Suresh Ambudkar, USA
Ivet Bahar, USA
Scott C. Blanchard, USA
Michael H. Baumann, USA
Liz Carpenter, United Kingdom
Peter Chiba, Austria
Thorben Cordes, The Netherlands
Raul R. Gainetdinov, Italy
Margaret Gnegy, USA
Peter Hinterdorfer, Austria
Edmund Kunji, United Kingdom
Hassane Mchaourab, USA
Joseph Mindell, USA
Sergei Noskov, Canada
Martin Pos, Germany
Rajini Rao, USA
Nico Reyes, France
Jeffrey D. Rothstein, USA
Avner Schlessinger, USA
Gerhard Schütz, Austria
Maria Sibilia, Austria
Gergely Szakacs, Austria
Bruno Stieger, Switzerland
Dirk Trauner, Germany
Michael Trauner, Austria
Hendrik van Veen, United Kingdom
Symposium 2014
Speakers:
Lucia Carvelli, USA
Farrukh A. Chaudhry, Norway
Gerhard Ecker, Austria
Volker Eulenburg, Germany
Michael Freissmuth, Austria
Aurelio Galli, USA
Ulrik Gether, Denmark
Ronald H. Kaback, USA
Mike Kavanaugh, USA
Ralf Kubitz, Germany
Manju Kurian, United Kingdom
Hiroyuki Kusuhara, Japan
Oliver Langer, Austria
Gaia Novarino, Austria
Daniela Pollak, Austria
Maarten Reith, USA
Jean-Louis Reymond, Switzerland
Rebecca Seal, USA
Igor Stagljar, Canada
Thomas Stockner, Austria
Yuichi Sugiyama, Japan
Giulio Superti-Furga, Austria
Stephan Urban, Germany
Ai Yamamoto, USA
Christine Ziegler, Germany
Symposium 2013
Speakers:
Konstantinos Beis, United Kingdom
Randy Blakely, USA
Peter Chiba, Austria
Susan P.C. Cole, Canada
Lynette C. Daws, USA
Raimund Dutzler, Switzerland
Keith Henry, USA
Jonathan Javitch, USA
Oliver Kudlacek, Austria
Karl Kuchler, Austria
Claus Juul Loland, Denmark
Poul Nissen, Denmark
Michael Robinson, USA
Gary Rudnick, USA
Erin Schuetz, USA
John Schuetz, USA
Gerhard Schuetz, Austria
Maria Sibilia, Austria
Steffen Sinning, Denmark
Harald Sitte, Austria
Emad Tajkhorshid, USA
Robert Tampé, Germany
Michael Trauner, Austria
Roxanne Vaughan, USA
Da-Neng Wang, US A
Klaus Wanner, Germany
Symposium 2012
Susan G. Amara, Pittsburgh, USA
Marc G. Caron, Durham, USA
Gerhard Ecker, Vienna, Austria
Ian Forster, Zürich, Switzerland
Michael Freissmuth, Vienna, Austria
Jana Haase, Dublin, Ireland
Peter Hinterdorfer, Linz, Austria
Habibeh Khoshbouei, Gainesville, USA
Michael Köttgen, Freiburg, Germany
Donald Miller, Seattle, USA
Oliver Langer, Vienna, Austria
Amy Hauck Newman, Baltimore, USA
Jeffrey Rothstein, Baltimore, USA
Balazs Sarkadi, Budapest, Hungary
Gergely Szakacs, Budapest, Hungary
Alan Tall, New York, USA
Kazumitsu Ueda, Kyoto, Japan
Symposium 2011
Speakers:
Jacob Andersen, Copenhagen, Denmark
Richard Callaghan, Oxford, United Kingdom
Peter Chiba, Vienna, Austria
Niels Christian Danbolt, Oslo, Norway
Aurelio Galli, Nashville, USA
Ulrik Gether, Copenhagen, Denmark
Baruch Kanner, Jerusalem, Israel
Haley Melikian, Worcester, USA
Manuel Palacin, Barcelona, Spain
Lukas Pezawas, Vienna, Austria
Hanne Poulsen, Aarhus, Denmark
Walter Sandtner, Vienna, Austria
Sander Smits, Düsseldorf, Germany
Bruno Stieger, Zürich, Switzerland
Tetsuya Terasaki, Sendai, Japan
Michael Trauner, Vienna, Austria
Symposium 2010
Speakers:
Elizabeth De Lange, Leiden, Netherland
Gerhard Ecker, Vienna, Austria
Michael Freissmuth, Vienna, Austria
Peter Hinterdorfer, Linz, Austria
Hermann Koepsell, Würzburg, Germany
Adriaan Lammertsma, Amsterdam, Netherland
Oliver Langer, Vienna, Austria
Peter Larsson, Miami, USA
Markus Müller, Vienna, Austria
Maarten E. Reith, New York, USA
Gary Rudnick, New Haven, USA
Kazumitsu Ueda, Kyoto, Japan
Harel Weinstein, New York, USA
Symposium 2009
Speakers:
Christoph Baumgartner, Vienna, Austria
Frank Bernhard, Frankfurt, Germany
Randy Blakely, Nashville, TN, USA
Peter Chiba, Vienna, Austria
Volker Doetsch, Frankfurt, Germany
Robert Edwards, San Francisco, California, USA
Alexander Gottschalk, Frankfurt, Germany
Jonathan Javitch, New York, USA
Karl Kuchler, Vienna, Austria
Werner Kühlbrandt, Frankfurt, Germany
Wolfgang Löscher, Hannover, Germany
Lukas Pezawas, Vienna, Austria
Bert Poolmann, Nijenborh, The Netherlands
Shimon Schuldiner, Jerusalem, Israel
Harald Sitte, Vienna, Austria
Alexander Sorkin, Aurora, Colorado, USA
Peggy Stolt-Bergner, Vienna, Austria
Graham Warren, Vienna, Austria
Christine Ziegler, Frankfurt, Germany
Symposium 2008
Speakers:
Jürgen Bereiter-Hahn, Frankfurt, Germany
Gerhard Ecker, Vienna, Austria
Volker Eulenburg, Frankfurt, Germany
Michael Freissmuth, Vienna, Austria
Aurelio Galli, Nashville, TN, USA
Clemens Gaubitz, Frankfurt, Germany
Ulrik Gether, Copenhagen, Denmark
Peter Hinterdorfer, Linz, Austria
Kaspar Hollenstein, Zürich, Switzerland
Baruch Kanner, Jerusalem, Israel
Karl Kuchler, Vienna, Austria
Adriaan A. Lammertsma, Amsterdam, The Netherlands
Oliver Langer, Vienna, Austria
Donald W. Miller, Winnipeg, MB, Canada
Lutz Schmitt, Frankfurt, Germany
Arne Schousboe, Copenhagen, Denmark
Mike Strauss, Frankfurt, Germany
Robert Tampé, Frankfurt, Germany
Christopher Tate, Cambridge, United Kingdom
Matthäus Willeit, Vienna, Austria
Seminar series "Colloquia in membrane transport"
"Colloquia in Transmembrane transport": a monthly seminar series of reputed, invited international speakers. In ten years of "Colloquia in Transmembrane Transport" we hosted in total 65 speakers from 13 countries:
- International speakers from United States of America (15) and Canada (1)
- European speakers from Austria (15, thereof 12 from fellow laboratories), Denmark (5), France (1), Germany (12), Hungary (4), Italy (1), The Netherlands (4), Portugal (1), Sweden (1), Switzerland (3), United Kingdom (2)
A detailed overview of all speakers and their lectures can be found here.
Publications
Original papers 2019
Adler P, Teskey CJ, Kaiser D, Holy M, Sitte HH, Maulide N.
α-Fluorination of carbonyls with nucleophilic fluorine.
Nat Chem. 2019 Apr;11(4):329-334. doi: 10.1038/s41557-019-0215-z. Epub 2019 Mar 4.
Das AK, Kudlacek O, Baumgart F, Jaentsch K, Stockner T, Sitte HH, Schütz GJ.
Dopamine transporter forms stable dimers in the live cell plasma membrane in a phosphatidylinositol 4,5-bisphosphate-independent manner.
J Biol Chem. 2019 Apr 5;294(14):5632-5642. doi: 10.1074/jbc.RA118.006178. Epub 2019 Jan 31.
Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner W.
A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2.
J Gen Physiol. 2019 Aug 5;151(8):1035-1050. doi: 10.1085/jgp.201912318. Epub 2019 Jul 3.
Kasture AS, Bartel D, Steinkellner T, Sucic S, Hummel T, Freissmuth M.
Distinct contribution of axonal and somatodendritic serotonin transporters in drosophila olfaction.
Neuropharmacology. 2019 Mar 6. pii: S0028-3908(19)30084-X. doi: 10.1016/j.neuropharm.2019.03.007. [Epub ahead of print]
Kovalchuk V, Samluk Ł, Juraszek B, Jurkiewicz-Trząska D, Sucic S, Freissmuth M, Nałęcz KA.
Trafficking of the amino acid transporter B0,+ (SLC6A14) to the plasma membrane involves an exclusive interaction with SEC24C for its exit from the endoplasmic reticulum.
Biochim Biophys Acta Mol Cell Res. 2019 Feb;1866(2):252-263. doi: 10.1016/j.bbamcr.2018.11.005. Epub 2018 Nov 14.
Mayer FP, Cintulova D, Pittrich DA, Wimmer L, Luethi D, Holy M, Jaentsch K, Tischberger S, Gmeiner G, Hoener MC, Liechti ME, Mihovilovic MD, Sitte HH.
Stereochemistry of phase-1 metabolites of mephedrone determines their effectiveness as releasers at the serotonin transporter.
Neuropharmacology. 2019 Apr;148:199-209. doi: 10.1016/j.neuropharm.2018.12.032. Epub 2019 Jan 2.
Niello M, Cintulova D, Hellsberg E, Jäntsch K, Holy M, Ayatollahi LH, Cozzi NV, Freissmuth M, Sandtner W, Ecker GF, Mihovilovic MD, Sitte HH.
para-Trifluoromethyl-methcathinone is an allosteric modulator of the serotonin transporter.
Neuropharmacology. 2019 Apr 24. pii: S0028-3908(19)30137-6. doi: 10.1016/j.neuropharm.2019.04.021. [Epub ahead of print]
Rakvács Z, Kucsma N, Gera M, Igriczi B, Kiss K, Barna J, Kovács D, Vellai T, Bencs L, Reisecker JM, Szoboszlai N, Szakács G.
The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification.
Cell Mol Life Sci. 2019 May 3. doi: 10.1007/s00018-019-03105-5. [Epub ahead of print]
Reisinger SN, Kong E, Molz B, Humberg T, Sideromenos S, Cicvaric A, Steinkellner T, Yang JW, Cabatic M, Monje FJ, Sitte HH, Nichols BJ, Pollak DD.
Flotillin-1 interacts with the serotonin transporter and modulates chronic corticosterone response.
Genes Brain Behav. 2019 Feb;18(2):e12482. doi: 10.1111/gbb.12482. Epub 2018 May 20.
Ropek N, Al-Serori H, Mišík M, Nersesyan A, Sitte HH, Collins AR, Shaposhnikov S, Knasmüller S, Kundi M, Ferk F.
Methamphetamine ("crystal meth") causes induction of DNA damage and chromosomal aberrations in human derived cells.
Food Chem Toxicol. 2019 Jun;128:1-7. doi: 10.1016/j.fct.2019.03.035. Epub 2019 Mar 22.
Saha K, Li Y, Holy M, Lehner KR, Bukhari MO, Partilla JS, Sandtner W, Sitte HH, Baumann MH.
The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.
Psychopharmacology (Berl). 2019 Mar;236(3):953-962. doi: 10.1007/s00213-018-5075-5. Epub 2018 Oct 22
Windt T, Tóth S, Patik I, Sessler J, Kucsma N, Szepesi Á, Zdrazil B, Özvegy-Laczka C, Szakács G.
Identification of anticancer OATP2B1 substrates by an in vitro triple-fluorescence-based cytotoxicity screen.
Arch Toxicol. 2019 Apr;93(4):953-964. doi: 10.1007/s00204-019-02417-6. Epub 2019 Mar 12.
Yang JW, Larson G, Konrad L, Shetty M, Holy M, Jäntsch K, Kastein M, Heo S, Erdem FA, Lubec G, Vaughan RA, Sitte HH, Foster JD.
Dephosphorylation of human dopamine transporter at threonine 48 by protein phosphatase PP1/2A up-regulates transport velocity.
J Biol Chem. 2019 Mar 8;294(10):3419-3431. doi: 10.1074/jbc.RA118.005251. Epub 2018 Dec 26.
Reviews/book chapters 2019
Jain S, Ecker GF.
In Silico Approaches to Predict Drug-Transporter Interaction Profiles: Data Mining, Model Generation, and Link to Cholestasis.
Part of the Methods in Molecular Biology book series (MIMB, volume 1981)
Methods Mol Biol. 2019;1981:383-396. doi: 10.1007/978-1-4939-9420-5_26.
Print ISBN 978-1-4939-9419-9; Online ISBN 978-1-4939-9420-5.
Original papers 2018
Bauer M, Matsuda A, Wulkersdorfer B, Philippe C, Traxl A, Özvegy-Laczka C, Stanek J, Nics L, Klebermass EM, Poschner S, Jäger W, Patik I, Bakos É, Szakács G, Wadsak W, Hacker M, Zeitlinger M, Langer O.
Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.
Clin Pharmacol Ther. 2018 Jul;104(1):139-147. doi: 10.1002/cpt.888.
Bergam P, Reisecker JM, Rakvács Z, Kucsma N, Raposo G, Szakacs G, van Niel G.
ABCB6 Resides in Melanosomes and Regulates Early Steps of Melanogenesis Required for PMEL Amyloid Matrix Formation.
J Mol Biol. 2018 Oct 12;430(20):3802-3818. doi: 10.1016/j.jmb.2018.06.033.
Burtscher V, Hotka M, Li Y, Freissmuth M, Sandtner W.
A label-free approach to detect ligand binding to cell surface proteins in real time.
Elife. 2018 Apr 26;7. pii: e34944. doi: 10.7554/eLife.34944.
Danzberger J, Donovan M, Rankl C, Zhu R, Vicic S, Baltenneck C, Enea R, Hinterdorfer P, Luengo GS.
Glycan distribution and density in native skin's stratum corneum.
Skin Res Technol. 2018 Aug;24(3):450-458. doi: 10.1111/srt.12453.
Dhar D, Antonucci L, Nakagawa H, Kim JY, Glitzner E, Caruso S, Shalapour S, Yang L, Valasek MA, Lee S, Minnich K, Seki E, Tuckermann J, Sibilia M, Zucman-Rossi J, Karin M.
Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling.
Cancer Cell. 2018 Jun 11;33(6):1061-1077.e6. doi: 10.1016/j.ccell.2018.05.003.
Estrada-Tejedor R, Ecker GF.
Predicting drug resistance related to ABC transporters using unsupervised Consensus Self-Organizing Maps.
Sci Rep. 2018 May 1;8(1):6803. doi: 10.1038/s41598-018-25235-9.
Fuchs CD, Paumgartner G, Mlitz V, Kunczer V, Halilbasic E, Leditznig N, Wahlström A, Ståhlman M, Thüringer A, Kashofer K, Stojakovic T, Marschall HU, Trauner M.
Colesevelam attenuates cholestatic liver and bile duct injury in Mdr2-/- mice by modulating composition, signalling and excretion of faecal bile acids.
Gut. 2018 Sep;67(9):1683-1691. doi: 10.1136/gutjnl-2017-314553.
Gautherot J, Claudel T, Cuperus F, Fuchs CD, Falguières T, Trauner M.
Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice.
J Lipid Res. 2018 Sep;59(9):1610-1619. doi: 10.1194/jlr.M084145.
Hasenhuetl PS, Bhat S, Mayer FP, Sitte HH, Freissmuth M, Sandtner W.
A kinetic account for amphetamine-induced monoamine release.
J Gen Physiol. 2018 Feb 9. pii: jgp.201711915. doi: 10.1085/jgp.201711915.
Jain S, Grandits M, Ecker GF.
Interspecies comparison of putative ligand binding sites of human, rat and mouse P-glycoprotein.
Eur J Pharm Sci. 2018 Sep 15;122:134-143. doi: 10.1016/j.ejps.2018.06.022. Epub 2018 Jun 22.
Jain S, Kotsampasakou E, Ecker GF.
Comparing the performance of meta-classifiers-a case study on selected imbalanced data sets relevant for prediction of liver toxicity.
J Comput Aided Mol Des. 2018 May;32(5):583-590. doi: 10.1007/s10822-018-0116-z.
Jayaraman K, Morley AN, Szöllősi D, Wassenaar TA, Sitte HH, Stockner T.
Dopamine transporter oligomerization involves the scaffold domain, but spares the bundle domain.
PLoS Comput Biol. 2018 Jun 6;14(6):e1006229. doi: 10.1371/journal.pcbi.1006229. eCollection 2018 Jun.
Lemberger UJ, Fuchs CD, Schöfer C, Bileck A, Gerner C, Stojakovic T, Taketo MM, Trauner M, Egger G, Österreicher CH.
Hepatocyte specific expression of an oncogenic variant of β-catenin results in lethal metabolic dysfunction in mice.
Oncotarget. 2018 Jan 30;9(13):11243-11257. doi: 10.18632/oncotarget.24346.
Lichtenegger M, Tiapko O, Svobodova B, Stockner T, Glasnov TN, Schreibmayer W, Platzer D, de la Cruz GG, Krenn S, Schober R, Shrestha N, Schindl R, Romanin C, Groschner K.
An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel.
Nat Chem Biol. 2018 Apr;14(4):396-404. doi: 10.1038/s41589-018-0015-6.
Linder M, Glitzner E, Srivatsa S, Bakiri L, Matsuoka K, Shahrouzi P, Dumanic M, Novoszel P, Mohr T, Langer O, Wanek T, Mitterhauser M, Wagner EF, Sibilia M.
EGFR is required for FOS-dependent bone tumor development via RSK2/CREB signaling.
EMBO Mol Med. 2018 Oct 25. pii: e9408. doi: 10.15252/emmm.201809408.
Maier J, Mayer FP, Luethi D, Holy M, Jäntsch K, Reither H, Hirtler L, Hoener MC, Liechti ME, Pifl C, Brandt SD, Sitte HH.
The psychostimulant (±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters.
Neuropharmacology. 2018 Aug;138:282-291. doi: 10.1016/j.neuropharm.2018.06.018.
Marsh APL, Novarino G, Lockhart PJ, Leventer RJ.
CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63.
Eur J Hum Genet. 2018 Aug 8. doi: 10.1038/s41431-018-0231-2.
Mayer FP, Burchardt NV, Decker AM, Partilla JS, Li Y, McLaughlin G, Kavanagh PV, Sandtner W, Blough BE, Brandt SD, Baumann MH, Sitte HH.
Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family.
Neuropharmacology. 2018 May 15;134(Pt A):149-157. doi: 10.1016/j.neuropharm.2017.10.006.
Mayer FP, Schmid D, Holy M, Daws LC, Sitte HH.
"Polytox" synthetic cathinone abuse: A potential role for organic cation transporter 3 in combined cathinone-induced efflux.
Neurochem Int. 2018 Sep 21. pii: S0197-0186(18)30343-7. doi: 10.1016/j.neuint.2018.09.008.
Mayer FP, Schmid D, Owens WA, Gould GG, Apuschkin M, Kudlacek O, Salzer I, Boehm S, Chiba P, Williams PH, Wu HH, Gether U, Koek W, Daws LC, Sitte HH.
An unsuspected role for organic cation transporter 3 in the actions of amphetamine.
Neuropsychopharmacology. 2018 Nov; 43(12):2408-2417. doi: 10.1038/s41386-018-0053-5.
Robson JP, Wagner B, Glitzner E, Heppner FL, Steinkellner T, Khan D, Petritsch C, Pollak DD, Sitte HH, Sibilia M.
Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain.
FEBS J. 2018 Sep;285(17):3175-3196. doi: 10.1111/febs.14603.
Silverstein N, Sliman A, Stockner T, Kanner BI.
Both reentrant loops of the sodium-coupled glutamate transporters contain molecular determinants of cation selectivity.
J Biol Chem. 2018 Sep 14;293(37):14200-14209. doi: 10.1074/jbc.RA118.003261.
Singh N, Scalise M, Galluccio M, Wieder M, Seidel T, Langer T, Indiveri C, Ecker GF.
Discovery of Potent Inhibitors for the Large Neutral Amino Acid Transporter 1 (LAT1) by Structure-Based Methods.
Int J Mol Sci. 2018 Dec 21;20(1). pii: E27. doi: 10.3390/ijms20010027.
Szöllősi D, Szakács G, Chiba P, Stockner T.
Dissecting the Forces that Dominate Dimerization of the Nucleotide Binding Domains of ABCB1.
Biophys J. 2018 Jan 23;114(2):331-342. doi: 10.1016/j.bpj.2017.11.022.
Reviews/book chapters 2018
Freissmuth M, Stockner T, Sucic S.
SLC6 Transporter Folding Diseases and Pharmacochaperoning.
Handb Exp Pharmacol. 2018;245:249-270. doi: 10.1007/164_2017_71. Review.
Kasture AS, Hummel T, Sucic S, Freissmuth M.
Big Lessons from Tiny Flies: Drosophila melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems.
Int J Mol Sci. 2018 Jun 16;19(6). pii: E1788. doi: 10.3390/ijms19061788. Review.
Maier J, Mayer FP, Brandt SD, Sitte HH.
DARK Classics in Chemical Neuroscience: Aminorex Analogues.
ACS Chem Neurosci. 2018 Oct 5. doi: 10.1021/acschemneuro.8b00415.
Singh N, Ecker GF.
Insights into the Structure, Function, and Ligand Discovery of the Large Neutral Amino Acid Transporter 1, LAT1.
Int J Mol Sci. 2018 Apr 24;19(5). pii: E1278. doi: 10.3390/ijms19051278. Review.
Szöllősi D, Rose-Sperling D, Hellmich UA, Stockner T.
Comparison of mechanistic transport cycle models of ABC exporters.
Biochim Biophys Acta Biomembr. 2018 Apr;1860(4):818-832. doi: 10.1016/j.bbamem.2017.10.028. Epub 2017 Oct 31. Review.
Zhu R, Gruber HJ, Hinterdorfer P.
Two Ligand Binding Sites in Serotonin Transporter Revealed by Nanopharmacological Force Sensing.
Methods Mol Biol. 2018;1814:19-33. doi: 10.1007/978-1-4939-8591-3_2.
Original papers 2017
Amberg N, Holcmann M, Stulnig G, Glitzner E, M. Sibilia.
Effects of Depilation Methods on Imiquimod-Induced Skin Inflammation in Mice.
J Invest Dermatol. 2017 Feb;137(2):528-531. doi: 10.1016/j.jid.2016.09.018.
Anderluh A, Hofmaier T, Klotzsch E, Kudlacek O, Stockner T, Sitte HH, Schütz GJ.
Direct PIP2 binding mediates stable oligomer formation of the serotonin transporter.
Nat Commun. 2017 Jan 19;8:14089. doi: 10.1038/ncomms14089.
Arab JP, Karpen SJ, Dawson PA, Arrese M, Trauner M.
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives.
Hepatology. 2017 Jan;65(1):350-362. doi: 10.1002/hep.28709.
Asjad HMM, Kasture A, El-Kasaby A, Sackel M, Hummel T, Freissmuth M, Sucic S.
Pharmacochaperoning in a Drosophila model system rescues human dopamine transporter variants associated with infantile/juvenile parkinsonism.
J Biol Chem. 2017 Nov 24;292(47):19250-19265. doi: 10.1074/jbc.M117.797092.
Bauer M, Karch R, Tournier N, Cisternino S, Wadsak W, Hacker M, Marhofer P, Zeitlinger M, Langer O.
Assessment of P-glycoprotein Transport Activity at the Human Blood-Retinal Barrier with (R)-11C-verapamil PET.
J Nucl Med. 2017 Apr;58(4):678-681. doi: 10.2967/jnumed.116.182147.
Bauer M, Wulkersdorfer B, Karch R, Philippe C, Jäger W, Stanek J, Wadsak W, Hacker M, Zeitlinger M, Langer O.
Effect of P-glycoprotein inhibition at the blood-brain barrier on brain distribution of (R)-[11 C]verapamil in elderly versus young subjects.
Br J Clin Pharmacol. 2017 Sep;83(9):1991-1999. doi: 10.1111/bcp.13301.
Bhat S, Hasenhuetl PS, Kasture A, El-Kasaby A, Baumann MH, Blough BE, Sucic S, Sandtner W, Freissmuth M.
Conformational state interactions provide clues to the pharmacochaperone potential of serotonin transporter partial substrates.
J Biol Chem. 2017 Oct 6;292(40):16773-16786. doi: 10.1074/jbc.M117.794081.
Fuchs CD, Claudel T, Scharnagl H, Stojakovic T, Trauner M.
FXR controls CHOP expression in steatohepatitis.
FEBS Lett. 2017 Oct;591(20):3360-3368. doi: 10.1002/1873-3468.12845.
Fuchs CD, Paumgartner G, Wahlström A, Schwabl P, Reiberger T, Leditznig N, Stojakovic T, Rohr-Udilova N, Chiba P, Marschall HU, Trauner M.
Metabolic preconditioning protects BSEP/ABCB11-/- mice against cholestatic liver injury.
J Hepatol. 2017 Jan;66(1):95-101. doi: 10.1016/j.jhep.2016.08.017.
Füredi A, Szebényi K, Tóth S, Cserepes M, Hámori L, Nagy V, Karai E, Vajdovich P, Imre T, Szabó P, Szüts D, Tóvári J, Szakács G.
Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer.
J Control Release. 2017 Sep 10;261:287-296. doi: 10.1016/j.jconrel.2017.07.010.
Jain S, Grandits M, Richter L, Ecker GF.
Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP.
J Comput Aided Mol Des. 2017 May 19. doi: 10.1007/s10822-017-0021-x
Jørgensen L, Al-Khawaja A, Kickinger S, Vogensen SB, Skovgaard-Petersen J, Rosenthal E, Borkar N, Löffler R, Madsen KK, Bräuner-Osborne H, Schousboe A, Ecker GF, Wellendorph P, Clausen RP.
Structure-Activity Relationship, Pharmacological Characterization, and Molecular Modeling of Noncompetitive Inhibitors of the Betaine/γ-Aminobutyric Acid Transporter 1 (BGT1).
J Med Chem. 2017 Nov 9;60(21):8834-8846. doi: 10.1021/acs.jmedchem.7b00924.
Kern C, Erdem FA, El-Kasaby A, Sandtner W, Freissmuth M, Sucic S.
The N-terminus specifies the switch between transport modes of the human serotonin transporter.
J Biol Chem.2017 Mar 3;292(9):3603-3613. doi: 10.1074/jbc.M116.771360.
Kotsampasakou E, Ecker GF.
Predicting Drug-Induced Cholestasis with the Help of Hepatic Transporters-An in Silico Modeling Approach.
J Chem Inf Model. 2017 Mar 27;57(3):608-615. doi: 10.1021/acs.jcim.6b00518.
Kotsampasakou E, Escher SE, Ecker GF.
Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions.
Data Brief. 2017 Feb 10;11:204-207. doi: 10.1016/j.dib.2017.02.009.
Kotsampasakou E, Escher SE, Ecker GF.
Linking organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3) interaction profiles to hepatotoxicity - The hyperbilirubinemia use case.
Eur J Pharm Sci. 2017 Jan 4;100:9-16. doi: 10.1016/j.ejps.2017.01.002.
Kotsampasakou E, Montanari F, Ecker GF.
Predicting drug-induced liver injury: The importance of data curation.
Toxicology. 2017 Aug 15;389:139-145. doi: 10.1016/j.tox.2017.06.003.
Khunweeraphong N, Stockner T, Kuchler K.
The structure of the human ABC transporter ABCG2 reveals a novel mechanism for drug extrusion.
Sci Rep. 2017 Oct 23;7(1):13767. doi: 10.1038/s41598-017-11794-w.
Li Y, Mayer FP, Hasenhuetl PS, Burtscher V, Schicker K, Sitte HH, Freissmuth M, Sandtner W.
Occupancy of the Zinc Binding-site by Transition Metals decreases the Substrate Affinity of the Human Dopamine Transporter by an Allosteric Mechanism.
J Biol Chem. 2017 Mar 10;292(10):4235-4243. doi: 10.1074/jbc.M116.760140.
Minutti CM, Drube S, Blair N, Schwartz C, McCrae JC, McKenzie AN, Kamradt T, Mokry M, Coffer PJ, Sibilia M, Sijts AJ, Fallon PG, Maizels RM, Zaiss DM.
Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion.
Immunity. 2017 Oct 17;47(4):710-722.e6. doi: 10.1016/j.immuni.2017.09.013.
Montanari F, Zdrazil B.
How Open Data Shapes In Silico Transporter Modeling.
Molecules 2017, 22(3), 422; doi:10.3390/molecules22030422
Schwabl P, Hambruch E, Seeland BA, Hayden H, Wagner M, Garnys L, Strobel B, Schubert TL, Riedl F, Mittereger D, Burnet M, Starlinger P, Oberhuber G, Deuschle U, Rohr-Udilova N, Podesser BK, Peck-Radosavljevic M, Reiberger T, Kremoser C, Trauner M.
The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.
J Hepatol. 2017 Apr;66(4):724-733. doi: 10.1016/j.jhep.2016.12.005
Sohail MI, Schmid D, Wlcek K, Spork M, Szakács G, Trauner M, Stockner T, Chiba P.
Molecular Mechanism of Taurocholate Transport by the Bile Salt Export Pump, an ABC Transporter Associated with Intrahepatic Cholestasis.
Mol Pharmacol. 2017 Oct;92(4):401-413. doi: 10.1124/mol.117.108688.
Spork M, Sohail MI, Schmid D, Ecker GF, Chiba P, Stockner T.
Folding correction of ABC-transporter ABCB1 by pharmacological chaperones: a mechanistic concept.
Pharmacol Res Perspect. 2017 May 26;5(3):e00325. doi: 10.1002/prp2.325. eCollection 2017 Jun.
Tournier N, Goutal S, Auvity S, Traxl A, Mairinger S, Wanek T, Helal OB, Buvat I, Soussan M, Caillé F, Langer O.
Strategies to inhibit ABCB1- and ABCG2-mediated efflux transport of erlotinib at the blood-brain barrier: a PET study in non-human primates.
J Nucl Med. 2017 Jan;58(1):117-122. doi: 10.2967/jnumed.116.178665.
Seidel RA, Claudel T, Schleser FA, Ojha NK, Westerhausen M, Nietzsche S, Sponholz C, Cuperus F, Coldewey SM, Heinemann SH, Pohnert G, Trauner M, Bauer M.
Impact of higher-order heme degradation products on hepatic function and hemodynamics.
J Hepatol. 2017 Aug;67(2):272-281. doi: 10.1016/j.jhep.2017.03.037
Traxl A, Komposch K, Glitzner E, Wanek T, Mairinger S, Langer O, Sibilia M.
Hepatocyte-Specific Deletion of EGFR in Mice Reduces Hepatic Abcg2 Transport Activity Measured by [11C]erlotinib and Positron Emission Tomography.
Drug Metab Dispos. 2017 Oct;45(10):1093-1100. doi: 10.1124/dmd.117.077081.
Reviews/book chapters 2017
Asjad HMM, Nasrollahi-Shirazi S, Sucic S, Freissmuth M, Nanoff C.
Relax, Cool Down and Scaffold: How to Restore Surface Expression of Folding-Deficient Mutant GPCRs and SLC6 Transporters.
Int J Mol Sci. 2017 Nov 14;18(11). pii: E2416. doi: 10.3390/ijms18112416. Review.
Cuperus F, Gautherot J, Halilbasic E, Claudel T, Trauner M.
ABC Transporters Involved in Cholestasis,
in: Transporters as Drug Targets, Volume 70 - Methods and Principles in Medicinal Chemistry (2017).
Editors: Gerhard F. Ecker, Rasmus Clausen and Harald Sitte,
Wiley-VCH p119-166, ISBN: 978-3-527-33384-4
Ecker GF.
ABC Transporters: From Targets to Antitargets and Back,
in: Transporters as Drug Targets, Volume 70 - Methods and Principles in Medicinal Chemistry (2017).
Editors: Gerhard F. Ecker, Rasmus Clausen and Harald Sitte,
Wiley-VCH p107-118, ISBN: 978-3-527-33384-4
Haake D, Chiba P, Ecker GF.
Recent Advances in Structural Modeling of ABC Transporters,
in: Transporters as Drug Targets, Volume 70 - Methods and Principles in Medicinal Chemistry (2017).
Editors: Gerhard F. Ecker, Rasmus Clausen and Harald Sitte,
Wiley-VCH p167-178, ISBN: 978-3-527-33384-4
Kasture A, Stockner T, Freissmuth M, Sucic S.
An unfolding story: Small molecules remedy misfolded monoamine transporters.
Int J Biochem Cell Biol. 2017 Nov;92:1-5. doi: 10.1016/j.biocel.2017.09.004. Epub 2017 Sep 7. Review.
Kudlacek O, Hofmaier T, Luf A, Mayer FP, Stockner T, Nagy C, Holy M, Freissmuth M, Schmid R, Sitte HH.
Cocaine adulteration.
J Chem Neuroanat. 2017 Oct;83-84:75-81. doi: 10.1016/j.jchemneu.2017.06.001. Epub 2017 Jun 12. Review.
Lamprecht C, Strasser J, Chtcheglova LA, Köhler M, Posch S, Oh YJ, Zhu R, Ebner A, Hinterdorfer P.
Biomedical Sensing with the Atomic Force Microscope; Book chapter in: Nanotribology and Nanomechanics: An Introduction,
Pages 135-173, Springer International Publishing 2017, ISBN: 978-3-319-51433-8, doi: 10.1007/978-3-319-51433-8_4
Langer O,
PET imaging of ABC transporters at the blood-brain barrier,
In: Transporters as Drug Targets, Volume 70 - Methods and Principles in Medicinal Chemistry (2017).
Editors: Gerhard F. Ecker, Rasmus Clausen and Harald Sitte,
Wiley-VCH p179-198, ISBN: 978-3-527-33384-4
Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak-Rieder N, Sitte H, Willeit M.
Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence.
Eur J Neurosci. 2017 Jan;45(1):45-57. doi: 10.1111/ejn.13418 Review
Schroeder JC, Deliu E, Novarino G, Schmeisser MJ.
Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.
Adv Anat Embryol Cell Biol. 2017;224:189-211. doi: 10.1007/978-3-319-52498-6_10. Review.
Sitte HH, Stockner T, Freissmuth M.
The molecular basis of the interaction between drugs and neurotransmitter transporters,
In: Transporters as Drug Targets, Volume 70 - Methods and Principles in Medicinal Chemistry (2017).
Editors: Gerhard F. Ecker, Rasmus Clausen and Harald Sitte,
Wiley-VCH p53-68, ISBN: 978-3-527-33384-4
Trauner M, Fuchs CD, Halilbasic E, Paumgartner G.
New therapeutic concepts in bile acid transport and signaling for management of cholestasis.
Hepatology. 2017 Apr;65(4):1393-1404. doi: 10.1002/hep.28991. Review.
Original papers 2016
Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, Graffner H, Krones E, Fickert P, Wahlström A, Ståhlman M, Paumgartner G, Marschall HU, Trauner M.
Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis.
J Hepatol. 2016 Mar;64(3):674-81. doi: 10.1016/j.jhep.2015.10.024.
Bársony O, Szalóki G, Türk D, Tarapcsák S, Gutay-Tóth Z, Bacsó Z, Holb IJ, Székvölgyi L, Szabó G, Csanády L, Szakács G, Goda K.
A single active catalytic site is sufficient to promote transport in P-glycoprotein.
Sci Rep. 2016 Apr 27;6:24810. doi: 10.1038/srep24810.
Bauer M, Blaickner M, Philippe C, Wadsak W, Hacker M, Zeitlinger M, Langer O.
Whole-body Distribution and Radiation Dosimetry of 11C-Elacridar and 11C-Tariquidar in Humans.
J Nucl Med. 2016 Aug;57(8):1265-8. doi: 10.2967/jnumed.116.175182.
Bauer M, Römermann K, Karch R, Wulkersdorfer B, Stanek J, Philippe C, Maier-Salamon A, Haslacher H, Jungbauer C, Wadsak W, Jäger W, Löscher W, Hacker M, Zeitlinger M, Langer O.
A pilot PET study to assess the functional interplay between ABCB1 and ABCG2 at the human blood-brain barrier.
Clin Pharmacol Ther. 2016 Aug;100(2):131-41. doi: 10.1002/cpt.362.
Billesbølle CB, Mortensen JS, Sohail A, Schmidt SG, Shi L, Sitte HH, Gether U, Loland CJ.
Transition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter.
Nat Commun. 2016 Sep 28;7:12755. doi: 10.1038/ncomms12755.
Dallas S, Salphati L, Gomez-Zepeda D, Wanek T, Chen L, Chu X, Kunta J, Mezler M, Menet MC, Chasseigneaux S, Decleves X, Langer O, Pierre E, DiLoreto K, Hoft C, Laplanche L, Pang J, Pereira T, Andonian C, Simic D, Rode A, Yabut J, Zhang X, Scheer N.
Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model.
Mol Pharmacol. 2016 May;89(5):492-504. doi: 10.1124/mol.115.102079.
Fuchs CD, Schwabl P, Reiberger T, Trauner M.
Liver Capsule: FXR agonists against liver disease.
Hepatology. 2016 Nov;64(5):1773. doi: 10.1002/hep.28836.
Hasenhuetl PS, Freissmuth M, Sandtner W.
Electrogenic Binding of Intracellular Cations Defines a Kinetic Decision Point in the Transport Cycle of the Human Serotonin Transporter.
J Biol Chem. 2016 Dec 9;291(50):25864-25876.
Kasture A, El-Kasaby A, Szöllősi D, Asjad HM, Grimm A, Stockner T, Hummel T, Freissmuth M, Sucic S.
Functional rescue of a misfolded Drosophila melanogaster dopamine transporter mutant associated with a sleepless phenotype by pharmacological chaperones.
J Biol Chem. 2016 Aug 1. pii: jbc.M116.737551.
Lemberger UJ, Fuchs CD, Karer M, Haas S, Stojakovic T, Schöfer C, Marschall HU, Wrba F, Taketo MM, Egger G, Trauner M, Österreicher CH.
Hepatocyte specific expression of an oncogenic variant of β-catenin results in cholestatic liver disease.
Oncotarget. 2016 Dec 27;7(52):86985-86998. doi: 10.18632/oncotarget.13521.
Mayer FP, Wimmer L, Dillon-Carter O, Partilla JS, Burchardt NV, Mihovilovic MD, Baumann MH, Sitte HH.
Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters.
Br J Pharmacol. 2016 Sep;173(17):2657-68. doi: 10.1111/bph.13547.
Meyer BM, Huemer J, Rabl U, Boubela RN, Kalcher K, Berger A, Banaschewski T, Barker G, Bokde A, Büchel C, Conrod P, Desrivières S, Flor H, Frouin V, Gallinat J, Garavan H, Heinz A, Ittermann B, Jia T, Lathrop M, Martinot JL, Nees F, Rietschel M, Smolka MN, Bartova L, Popovic A, Scharinger C, Sitte HH, Steiner H, Friedrich MH, Kasper S, Perkmann T, Praschak-Rieder N, Haslacher H, Esterbauer H, Moser E, Schumann G, Pezawas L.
Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.
Brain Struct Funct. 2016 Jan;221(1):103-14. doi: 10.1007/s00429-014-0895-5.
Montanari F, Cseke A, Wlcek K, Ecker GF.
Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors.
J Biomol Screen. 2016 Jul 8. pii: 1087057116657513.
Montanari F, Pinto M, Khunweeraphong N, Wlcek K, Sohail MI, Noeske T, Boyer S, Chiba P, Stieger B, Kuchler K, Ecker GF.
Flagging Drugs That Inhibit the Bile Salt Export Pump.
Mol Pharm. 2016 Jan 4;13(1):163-71. doi: 10.1021/acs.molpharmaceut.5b00594.
Montanari F, Zdrazil B, Digles D, Ecker GF.
Selectivity profiling of BCRP versus P-gp inhibition: from automated collection of polypharmacology data to multi-label learning.
J Cheminform. 2016 Feb 4;8:7. doi: 10.1186/s13321-016-0121-y.
Sandtner W, Stockner T, Hasenhuetl PS, Partilla JS, Seddik A, Zhang Y, Cao J, Holy M, Steinkellner T, Rudnick G, Baumann MH, Ecker GF, Newman AH, Sitte HH.
Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters.
Mol Pharmacol. 2016 Jan;89(1):165-75. doi: 10.1124/mol.115.101394.
Sase A, Aher YD, Saroja SR, Ganesan MK, Sase S, Holy M, Höger H, Bakulev V, Ecker GF, Langer T, Sitte HH, Leban J, Lubec G.
A heterocyclic compound CE-103 inhibits dopamine reuptake and modulates dopamine transporter and dopamine D1-D3 containing receptor complexes.
Neuropharmacology. 2016 Mar;102:186-96. doi: 10.1016/j.neuropharm.2015.07.039.
Schwarz T, Montanari F, Cseke A, Wlcek K, Visvader L, Palme S, Chiba P, Kuchler K, Urban E, Ecker GF.
Subtle Structural Differences Trigger Inhibitory Activity of Propafenone Analogues at the Two Polyspecific ABC Transporters: P-Glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP).
ChemMedChem. 2016 Jun 20;11(12):1380-94. doi: 10.1002/cmdc.201500592.
Seddik A, Geerke DP, Stockner T, Holy M, Kudlacek O, Cozzi NV, Ruoho AE, Sitte HH, Ecker GF.
Combined Simulation and Mutation Studies to Elucidate Selectivity of Unsubstituted Amphetamine-like Cathinones at the Dopamine Transporter.
Mol Inform. 2016 Nov 8. doi: 10.1002/minf.201600094.
Sohail A, Jayaraman K, Venkatesan S, Gotfryd K, Daerr M, Gether U, Loland CJ, Wanner KT, Freissmuth M, Sitte HH, Sandtner W, Stockner T.
The Environment Shapes the Inner Vestibule of LeuT.
PLoS Comput Biol. 2016 Nov 11;12(11):e1005197. doi: 10.1371/journal.pcbi.1005197.
Tărlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G.
Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.
Cell. 2016 Dec 1;167(6):1481-1494.e18. doi: 10.1016/j.cell.2016.11.013.
Wanek T, Halilbasic E, Visentin M, Mairinger S, Römermann K, Stieger B, Kuntner C, Müller M, Langer O, Trauner M.
Influence of 24-Nor-Ursodeoxycholic Acid on Hepatic Disposition of [(18)F]Ciprofloxacin, a Positron Emission Tomography Study in Mice.
J Pharm Sci. 2016 Jan;105(1):106-12. doi: 10.1016/j.xphs.2015.11.014.
Zdrazil B, Hellsberg E, Viereck M, Ecker GF.
From linked open data to molecular interaction: studying selectivity trends for ligands of the human serotonin and dopamine transporter.
Medchemcomm. 2016 Sep 14;7(9):1819-1831.
Zhu R, Sinwel D, Hasenhuetl PS, Saha K, Kumar V, Zhang P, Rankl C, Holy M, Sucic S, Kudlacek O, Karner A, Sandtner W, Stockner T, Gruber HJ, Freissmuth M, Hauck Newman A, Sitte HH, Hinterdorfer P.
Nanopharmacological Force Sensing to Reveal Allosteric Coupling in Transporter Binding Sites.
Angew Chem Int Ed Engl. 2016 Jan 26;55(5):1719-22. doi: 10.1002/anie.201508755.
Reviews/book chapters 2016
Fuchs CD, Traussnigg SA, Trauner M.
Nuclear Receptor Modulation for the Treatment of Nonalcoholic Fatty Liver Disease.
Semin Liver Dis. 2016 Feb;36(1):69-86. doi: 10.1055/s-0036-1571296. Review.
Halilbasic E, Fuchs C, Traussnigg S, Trauner M.
Farnesoid X Receptor Agonists and Other Bile Acid Signaling Strategies for Treatment of Liver Disease.
Dig Dis. 2016;34(5):580-8. doi: 10.1159/000445268. Review.
Jurik A, Seddik A, Ecker GF.
Experimental Data Guided Docking of Small Molecules into Homology Models of Neurotransmitter Transporters.
In: "Neurotransmitter Transporters - Investigative Methods" (2016), Series title: "Neuromethods" Vol 118, Springer Publishing group, Editors: Bönisch H. and Sitte H.H., pp 83-89, DOI10.1007/978-1-4939-3765-3_11, Print ISBN 978-1-4939-3763-9, Online ISBN 978-1-4939-3765-3
Khan D, Ronovsky M, Steinkellner T, Freissmuth M, Sitte HH, Pollak DD.
Animal models for depression and the mode of action of neurotransmitter transporter-blocking antidepressants.
In: "Neurotransmitter Transporters - Investigative Methods" (2016), Series title: "Neuromethods" Vol 118, Springer Publishing group, Editors: Bönisch H. and Sitte H.H., pp 189-202, DOI10.1007/978-1-4939-3765-3_11, Print ISBN 978-1-4939-3763-9, Online ISBN 978-1-4939-3765-3
Langer O.
Use of PET Imaging to Evaluate Transporter-Mediated Drug-Drug Interactions.
J Clin Pharmacol. 2016 Jul;56 Suppl 7:S143-56. doi: 10.1002/jcph.722.
Mayer FP, Luf A, Nagy C, Holy M, Schmid R, Freissmuth M, Sitte HH.
Application of a Combined Approach to Identify New Psychoactive Street Drugs and Decipher Their Mechanisms at Monoamine Transporters.
Curr Top Behav Neurosci. 2016 Dec 27. doi: 10.1007/7854_2016_63.
Steinkellner T, Mayer FP, Hofmaier T, Holy M, Montgomery T, Eisenrauch B, Freissmuth M, Sitte HH.
Tracer measurements to study outward transport by neurotransmitter transporters.
In: "Neurotransmitter Transporters - Investigative Methods" (2016), Series title: "Neuromethods" Vol 118, Springer Publishing group, Editors: Bönisch H. and Sitte H.H., pp 23-40, DOI10.1007/978-1-4939-3765-3_11, Print ISBN 978-1-4939-3763-9, Online ISBN 978-1-4939-3765-3
Sucic S, Kasture A, Mazhar Asjad HM, Kern C, El-Kasaby A, Freissmuth M.
When transporters fail to be transported: how to rescue folding-deficient SLC6 transporters.
J Neurol Neuromedicine. 2016 Dec 30;1(9):34-40.
Szöllősi D, Chiba P, Szakács G, Stockner T, Hegedűs T.
Mechanism of drug transport by ABC multidrug proteins in structural perspectives,
Royal Society Of Chemistry: Amino Acids, Peptides and Proteins, Volume 41, 2017, Pages 152-187;
Print ISBN: 978-1-78262-537-7; PDF eISBN: 978-1-78262-661-9; EPUB eISBN: 978-1-78801-081-8; DOI: 10.1039/9781782626619
Wagner M, Trauner M.
Recent advances in understanding and managing cholestasis.
F1000Res. 2016 Apr 19;5. pii: F1000 Faculty Rev-705. doi: 10.12688/f1000research.8012.1. Review.
Zhu C, Fuchs CD, Halilbasic E, Trauner M.
Bile acids in regulation of inflammation and immunity: friend or foe?
Clin Exp Rheumatol. 2016 Jul-Aug;34(4 Suppl 98):25-31. Review.
Original papers 2015
Amberg N, Holcmann M, Glitzner E, Novoszel P, Stulnig G, Sibilia M.
Mouse models of nonmelanoma skin cancer.
Methods Mol Biol. 2015;1267:217-50. doi: 10.1007/978-1-4939-2297-0_10.
Bartova L, Meyer BM, Diers K, Rabl U, Scharinger C, Popovic A, Pail G, Kalcher K, Boubela RN, Huemer J, Mandorfer D, Windischberger C, Sitte HH, Kasper S, Praschak-Rieder N, Moser E, Brocke B, Pezawas L,
Reduced default mode network suppression during a working memory task in remitted major depression.
J Psychiatr Res. 2015 May;64:9-18. doi: 10.1016/j.jpsychires.2015.02.025.
Bauer M, Karch R, Zeitlinger M, Philippe C, Römermann K, Stanek J, Maier-Salamon A, Wadsak W, Jäger W, Hacker M, Müller M, Langer O.
Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.
J Cereb Blood Flow Metab. 2015 May;35(5):743-6. doi: 10.1038/jcbfm.2015.19.
Boubela RN, Kalcher K, Huf W, Seidel EM, Derntl B, Pezawas L, Našel C, Moser E.
fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions.
Sci Rep. 2015 May 21;5:10499. doi: 10.1038/srep10499.
Brunner PM, Glitzner E, Reininger B, Klein I, Stary G, Mildner M, Uhrin P, Sibilia M, Stingl G.
CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin.
Exp Dermatol. 2015 Jul;24(7):522-8. doi: 10.1111/exd.12709.
Hasenhuetl PS, Schicker K, Koenig X, Li Y, Sarker S, Stockner T, Sucic S, Sitte HH, Freissmuth M, Sandtner W,
Ligand Selectivity among the Dopamine and Serotonin Transporters Specified by the Forward Binding Reaction.
Mol Pharmacol. 2015 Jul;88(1):12-8. doi: 10.1124/mol.115.099036.
Jurik A, Zdrazil B, Holy M, Stockner T, Sitte HH, Ecker GF,
A Binding Mode Hypothesis of Tiagabine Confirms Liothyronine Effect on γ-Aminobutyric Acid Transporter 1 (GAT1).
J Med Chem. 2015 Mar 12;58(5):2149-58. doi: 10.1021/jm5015428.
Kiss K, Kucsma N, Brozik A, Tusnady GE, Bergam P, van Niel G, Szakacs G,
Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein.
Biochem J. 2015 Apr 1;467(1):127-39. doi: 10.1042/BJ20141085.
Klotzsch E, Smorodchenko A, Löfler L, Moldzio R, Parkinson E, Schütz GJ, Pohl EE,
Superresolution microscopy reveals spatial separation of UCP4 and F0F1-ATP synthase in neuronal mitochondria.
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):130-5. doi: 10.1073/pnas.1415261112.
Koban F, El-Kasaby A, Häusler C, Stockner T, Simbrunner BM, Sitte HH, Freissmuth M, Sucic S,
A salt bridge linking the first intracellular loop with the C terminus facilitates the folding of the serotonin transporter.
J Biol Chem. 2015 May 22;290(21):13263-78. doi: 10.1074/jbc.M115.641357.
Kong E, Sucic S, Monje FJ, Savalli G, Diao W, Khan D, Ronovsky M, Cabatic M, Koban F, Freissmuth M, Pollak DD.
STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior.
Sci Rep. 2015 Mar 11;5:9009. doi: 10.1038/srep09009. Erratum in: Sci Rep. 2015;5:11965.
Kotsampasakou E, Brenner S, Jäger W, Ecker GF.
Identification of Novel Inhibitors of Organic Anion Transporting Polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) Using a Consensus Vote of Six Classification Models.
Mol Pharm. 2015 Dec 7;12(12):4395-404. doi: 10.1021/acs.molpharmaceut.5b00583.
Li Y, Hasenhuetl PS, Schicker K, Sitte HH, Freissmuth M, Sandtner W.
Dual Action of Zn2+ on the Transport Cycle of the Dopamine Transporter.
J Biol Chem. 2015 Dec 25;290(52):31069-76. doi: 10.1074/jbc.M115.688275.
Mueller M, Thorell A, Claudel T, Jha P, Koefeler H, Lackner C, Hoesel B, Fauler G, Stojakovic T, Einarsson C, Marschall HU, Trauner M,
Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.
J Hepatol. 2015 Jun;62(6):1398-404. doi: 10.1016/j.jhep.2014.12.034.
Neudorfer C, Seddik A, Shanab K, Jurik A, Rami-Mark C, Holzer W, Ecker G, Mitterhauser M, Wadsak W, Spreitzer H,
Synthesis and in silico evaluation of novel compounds for PET-based investigations of the norepinephrine transporter.
Molecules. 2015 Jan 20;20(1):1712-30. doi: 10.3390/molecules20011712.
Saha K, Partilla JS, Lehner KR, Seddik A, Stockner T, Holy M, Sandtner W, Ecker GF, Sitte HH, Baumann MH,
'Second-Generation' Mephedrone Analogs, 4-MEC and 4-MePPP, Differentially Affect Monoamine Transporter Function.
Neuropsychopharmacology. 2015 May;40(6):1321-31. doi: 10.1038/npp.2014.325.
Schmid D, Koenig X, Bulusu S, Schicker K, Freissmuth M, Sitte HH, Sandtner W,
The conservative view: is it necessary to implant a stent into the dopamine transporter?
Br J Pharmacol. 2015 Oct;172(19):4775-8. doi: 10.1111/bph.12766.
Sombetzki M, Fuchs CD, Fickert P, Österreicher CH, Mueller M, Claudel T, Loebermann M, Engelmann R, Langner C, Sahin E, Schwinge D, Guenther ND, Schramm C, Mueller-Hilke B, Reisinger EC, Trauner M.
24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis.
J Hepatol. 2015 Apr;62(4):871-8. doi: 10.1016/j.jhep.2014.11.020.
Stanek J, Mairinger S, Wanek T, Kuntner C, Müller M, Langer O,
Automated radiosynthesis of [(18)F]ciprofloxacin.
Appl Radiat Isot. 2015 May;99:133-7. doi: 10.1016/j.apradiso.2015.02.024.
Steinkellner T, Montgomery TR, Hofmaier T, Kudlacek O, Yang JW, Rickhag M, Jung G, Lubec G, Gether U, Freissmuth M, Sitte HH,
Amphetamine action at the cocaine- and antidepressant-sensitive serotonin transporter is modulated by αCaMKII.
J Neurosci. 2015 May 27;35(21):8258-71. doi: 10.1523/JNEUROSCI.4034-14.2015.
Erratum in: J Neurosci. 2015 Aug 19;35(33):11762.
Stiedl P, McMahon R, Blaas L, Stanek V, Svinka J, Grabner B, Zollner G, Kessler SM, Claudel T, Müller M, Mikulits W, Bilban M, Esterbauer H, Eferl R, Haybaeck J, Trauner M, Casanova E.
Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis.
Hepatology. 2015 Feb;61(2):613-26. doi: 10.1002/hep.27408.
Traxl A, Wanek T, Mairinger S, Stanek J, Filip T, Sauberer M, Müller M, Kuntner C, Langer O.,
Breast Cancer Resistance Protein and P-glycoprotein Influence In Vivo Disposition of 11C-Erlotinib.
J Nucl Med. 2015 Dec;56(12):1930-6. doi: 10.2967/jnumed.115.161273.
Vogensen SB, Jørgensen L, Madsen KK, Jurik A, Borkar N, Rosatelli E, Nielsen B, Ecker GF, Schousboe A, Clausen RP.
Structure activity relationship of selective GABA uptake inhibitors.
Bioorg Med Chem. 2015 May 15;23(10):2480-8. doi: 10.1016/j.bmc.2015.03.060.
Venkatesan S, Saha K, Sohail A, Sandtner W, Freissmuth M, Ecker GF, Sitte HH, Stockner T.
Refinement of the Central Steps of Substrate Transport by the Aspartate Transporter GltPh: Elucidating the Role of the Na2 Sodium Binding Site.
PLoS Comput Biol. 2015 Oct 20;11(10):e1004551. doi: 10.1371/journal.pcbi.1004551.
Wanek T, Traxl A, Bankstahl JP, Bankstahl M, Sauberer M, Langer O, Kuntner C,
[18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood-brain barrier.
Nucl Med Biol. 2015 Jul;42(7):585-9. doi: 10.1016/j.nucmedbio.2015.03.004.
Wanek T, Römermann K, Mairinger S, Stanek J, Sauberer M, Filip T, Traxl A, Kuntner C, Pahnke J, Bauer F, Erker T, Löscher W, Müller M, Langer O,
Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood-Brain Barrier Measured with Positron Emission Tomography.
Mol Pharm. 2015 Sep 8;12(9):3214-25. doi: 10.1021/acs.molpharmaceut.5b00168.
Reviews/book chapters 2015
Beuers U, Trauner M, Jansen P, Poupon R,
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond.
J Hepatol. 2015 Apr;62(1 Suppl):S25-37. doi: 10.1016/j.jhep.2015.02.023.
Chiba P, Ecker GF, Nasim F, Dönmez-Cakil Y.
Interaction of ABC Transporters with drugs.
Springer International Publishing ABC Transporters - 40 Years on, Part II, pp 135-151,
ISBN: 978-3-319-23475-5 (Print), 978-3-319-23476-2 (Online), doi: 10.1007/978-3-319-23476-2_7, 2015 Dec 17
Halilbasic E, Fuchs C, Hofer H, Paumgartner G, Trauner M.
Therapy of Primary Sclerosing Cholangitis--Today and Tomorrow.
Dig Dis. 2015;33 Suppl 2:149-63. doi: 10.1159/000440827.
Hellsberg E, Montanari F, Ecker GF.
The ABC of Phytohormone Translocation.
Planta Med. 2015 Apr;81(6):474-87. doi: 10.1055/s-0035-1545880.
Holcmann M, Amberg N, Drobits B, Glitzner E, Komposch K, Robson J, Savarese F, Srivatsa S, Stulnig G, Sibilia M.
Mouse Models of Receptor Tyrosine Kinases.
In: Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease.
Wheeler, Deric L., Yarden, Yosef (Eds.) Springer Science+Business Media New York (2015) pp279-438, doi: 10.1007/978-1-4939-2053-2_11,
Print ISBN978-1-4939-2052-5, Online ISBN978-1-4939-2053-2
Komposch K, Sibilia M.
EGFR Signaling in Liver Diseases.
Int J Mol Sci. 2015 Dec 29;17(1). pii: E30. doi: 10.3390/ijms17010030.
Krones E, Wagner M, Eller K, Rosenkranz AR, Trauner M, Fickert P.
Bile acid-induced cholemic nephropathy.
Dig Dis. 2015;33(3):367-75. doi: 10.1159/000371689.
Montanari F, Ecker GF.
Prediction of drug-ABC-transporter interaction--Recent advances and future challenges.
Adv Drug Deliv Rev. 2015 Jun 23;86:17-26. doi: 10.1016/j.addr.2015.03.001.
Sitte HH, Freissmuth M.
Amphetamines, new psychoactive drugs and the monoamine transporter cycle.
Trends Pharmacol Sci. 2015 Jan;36(1):41-50. doi: 10.1016/j.tips.2014.11.006.
Stockner T, Mullen A, MacMillan F.
Investigating the dynamic nature of the ABC transporters: ABCB1 and MsbA as examples for the potential synergies of MD theory and EPR applications.
Biochem Soc Trans. 2015 Oct;43(5):1023-32. doi: 10.1042/BST20150138.
Szakács G, Hegedűs T, Sarkadi B.
Inborn Errors of the Cellular Expression and Localization of ABCG2 and ABCB6. A Database for ABC Transporter Mutations.
Springer International Publishing ABC Transporters - 40 Years on, Part II, pp 341-355,
ISBN: 978-3-319-23475-5 (Print), 978-3-319-23476-2 (Online), doi: 10.1007/978-3-319-23476-2_14, 2015 Dec 17
Trauner M, Halilbasic E, Claudel T, Steinacher D, Fuchs C, Moustafa T, Pollheimer M, Krones E, Kienbacher C, Traussnigg S, Kazemi-Shirazi L, Munda P, Hofer H, Fickert P, Paumgartner G.
Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders.
Dig Dis. 2015;33(3):433-9. doi: 10.1159/000371904.
Sitte HH, Schütz GJ, Freissmuth M.
Cooperativity between individual transporter protomers: new data fuelling old complexes.
J Neurochem. 2015 Apr;133(2):163-6. doi: 10.1111/jnc.13086.
Original papers 2014
Anderluh A, Klotzsch E, Reismann AW, Brameshuber M, Kudlacek O, Newman AH, Sitte HH, Schütz GJ.
Single Molecule Analysis Reveals Coexistence of Stable Serotonin Transporter Monomers and Oligomers in the Live Cell Plasma Membrane.
J Biol Chem. 2014 Feb 14;289(7):4387-94. doi: 10.1074/jbc.M113.531632.
Anderluh A, Klotzsch E, Ries J, Reismann AW, Weber S, Fölser M, Koban F, Freissmuth M, Sitte HH, Schütz GJ.
Tracking single serotonin transporter molecules at the endoplasmic reticulum and plasma membrane.
Biophys J. 2014 May 6;106(9):L33-5. doi: 10.1016/j.bpj.2014.03.019.
Bauer M, Karch R, Zeitlinger M, Liu J, Koepp MJ, Asselin M-C, Sisodiya SM, Hainfellner JA, Wadsak W, Mitterhauser M, Müller M, Pataraia E, Langer O.
In-vivo P-glycoprotein function before and after epilepsy surgery.
Neurology. 2014 Oct 7;83(15):1326-31. doi: 10.1212/WNL.0000000000000858.
Baumann MH, Bulling S, Benaderet TS, Saha K, Ayestas MA, Partilla JS, Ali SF, Stockner T, Rothman RB, Sandtner W, Sitte HH.
Evidence for a Role of Transporter-Mediated Currents in the Depletion of Brain Serotonin Induced by Serotonin Transporter Substrates.
Neuropsychopharmacology. 2014 May;39(6):1355-65. doi: 10.1038/npp.2013.331.
Demetz E, Schroll A, Auer K, Heim C, Patsch JR, Eller P, Theurl M, Theurl I, Theurl M, Seifert M, Lener D, Stanzl U, Haschka D, Asshoff M, Dichtl S, Nairz M, Huber E, Stadlinger M, Moschen AR, Li X, Pallweber P, Scharnagl H, Stojakovic T, März W, Kleber ME, Garlaschelli K, Uboldi P, Catapano AL, Stellaard F, Rudling M, Kuba K, Imai Y, Arita M, Schuetz JD, Pramstaller PP, Tietge UJ, Trauner M, Norata GD, Claudel T, Hicks AA, Weiss G, Tancevski I.
The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism.
Cell Metab. 2014 Nov 4;20(5):787-98.
Donmez Cakil Y, Khunweeraphong N, Parveen Z, Schmid D, Artaker M, Ecker GF, Sitte HH, Pusch O, Stockner T, Chiba P.
Pore Exposed Tyrosine Residues of P-glycoprotein are Important Hydrogen Bonding Partners for Drugs.
Mol Pharmacol. 2014 Mar;85(3):420-8. doi: 10.1124/mol.113.088526.
El-Kasaby A, Koban F, Sitte HH, Freissmuth M, Sucic S.
A cytosolic relay of heat shock proteins HSP70-1A and HSP90β monitors the folding trajectory of the serotonin transporter.
J Biol Chem. 2014 Oct 17;289(42):28987-9000. doi: 10.1074/jbc.M114.595090.
Felts B, Pramod AB, Sandtner W, Burbach N, Bulling S, Sitte HH, Henry LK.
The two Na+ sites in the human serotonin transporter play distinct roles in the ion coupling and electrogenicity of transport.
J Biol Chem. 2014 Jan 17;289(3):1825-40. doi: 10.1074/jbc.M113.504654
Fenollar-Ferrer C, Stockner T, Schwarz TC, Pal A, Gotovina J, Hofmaier T, Jayaraman K, Adhikary S, Kudlacek O, Mehdipour AR, Tavoulari S, Rudnick G, Singh SK, Konrat R, Sitte HH, Forrest LR.
Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter.
Biochemistry. 2014 Aug 26;53(33):5444-60. doi: 10.1021/bi500637f.
Goldmann D, Montanari F, Richter L, Zdrazil B, Ecker GF.
Exploiting open data:a new era in pharmacoinformatics.
Future Med Chem. 2014 Apr;6(5):503-14. doi: 10.4155/fmc.14.13.
Griesauer I, Diao W, Ronovsky M, Elbau I, Sartori S, Singewald N, Pollak DD.
Circadian abnormalities in a mouse model of high trait anxiety and depression.
Ann Med. 2014 May;46(3):148-54. doi: 10.3109/07853890.2013.866440.
Hansen FH, Skjørringe T, Yasmeen S, Arends NV, Sahai MA, Erreger K, Andreassen TF, Holy M, Hamilton PJ, Neergheen V, Karlsborg M, Newman AH, Pope S, Heales SJ, Friberg L, Law I, Pinborg LH, Sitte HH, Loland C, Shi L, Weinstein H, Galli A, Hjermind LE, Møller LB, Gether U.
Missense dopamine transporter mutations associate with adult parkinsonism and ADHD.
J Clin Invest. 2014 Jul;124(7):3107-20. doi: 10.1172/JCI73778.
Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, Ecker GF, Schmid R, Sitte HH, Kudlacek O.
Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters.
Neurochem Int. 2014 Jul;73:32-41. doi: 10.1016/j.neuint.2013.11.010
Kalcher K, Boubela RN, Huf W, Bartova L, Kronnerwetter C, Derntl B, Pezawas L, Filzmoser P, Nasel C, Moser E.
The spectral diversity of resting-state fluctuations in the human brain.
PLoS One. 2014 Apr 11;9(4):e93375. doi: 10.1371/journal.pone.0093375.
Khan D, Fernando P, Cicvaric A, Berger A, Pollak A, Monje FJ, Hirsch J, Pollak DD.
Long-term effects of maternal immune activation on depression-like behavior in the mouse.
Transl Psychiatry. 2014 Feb 18;4:e363. doi: 10.1038/tp.2013.132.
Klepsch F, Poongavanam V, Ecker GF.
Ligand and structure-based classification models for Prediction of P-glycoprotein inhibitors.
J Chem Inf Model. 2014 Jan 27;54(1):218-29. doi: 10.1021/ci400289j.
Lanaya H, Natarajan A, Komposch K, Li L, Amberg N, Chen L, Wculek SK, Hammer M, Zenz R, Peck-Radosavljevic M, Sieghart W, Trauner M, Wang H, Sibilia M.
EGFR has a tumour-promoting role in liver macrophages during hepatocellular carcinoma formation.
Nat Cell Biol. 2014 Oct;16(10):972-81, 1-7. doi: 10.1038/ncb3031.
Michl J, Scharinger C, Zauner M, Kasper S, Freissmuth M, Sitte HH, Ecker GF, Pezawas L.
A multivariate approach linking reported side effects of clinical antidepressant and antipsychotic trials to in vitro binding affinities.
Eur Neuropsychopharmacol. 2014 Sep;24(9):1463-74. doi: 10.1016/j.euroneuro.2014.06.013.
Montanari F, Ecker GF.
BCRP inhibition - from data collection to ligand-based modeling.
Mol Inform. 2014 May;33(5):322-31. doi: 10.1002/minf.201400012.
Montgomery TR, Steinkellner T, Sucic S, Koban F, Schüchner S, Ogris E, Sitte HH, Freissmuth M.
Axonal Targeting of the Serotonin Transporter in Cultured Rat Dorsal Raphe Neurons Is Specified by SEC24C-Dependent Export from the Endoplasmic Reticulum.
J Neurosci. 2014 Apr 30;34(18):6344-51. doi: 10.1523/JNEUROSCI.2991-13.2014.
Parveen Z, Brunhofer G, Jabeen I, Erker T, Chiba P, Ecker GF.
Synthesis, biological evaluation and 3D-QSAR studies of new chalcone derivatives as inhibitors of human P-glycoprotein.
Bioorg Med Chem. 2014 Apr 1;22(7):2311-9. doi: 10.1016/j.bmc.2014.02.005.
Pollak DD, Minh BQ, Cicvaric A, Monje FJ.
A novel fibroblast growth factor receptor family member promotes neuronal outgrowth and synaptic plasticity in aplysia.
Amino Acids. 2014 Nov;46(11):2477-88. doi: 10.1007/s00726-014-1803-2.
Rabl U, Meyer B, Diers K, Bartova L, Berger A, Mandorfer D, Popovic A, Scharinger C, Huemer J, Kalcher K, Pail G, Haslacher H, Perkmann T, Windischberger C, Brocke B, Sitte HH, Pollak DD, Dreher JC, Kasper S, Praschak-Rieder N, Moser E, Esterbauer H, Pezawas L.
Additive Gene-Environment Effects on Hippocampal Structure in Healthy Humans.
J Neurosci. 2014 Jul 23;34(30):9917-26. doi: 10.1523/JNEUROSCI.3113-13.2014.
Rudashevskaya EL, Stockner T, Trauner M, Freissmuth M, Chiba P.
Pharmacological correction of misfolding of ABC proteins.
Drug Discov Today Technol. 2014 Jun;12:e87-94. doi: 10.1016/j.ddtec.2014.03.009
Sandtner W, Schmid D, Schicker K, Gerstbrein K, Koenig X, Mayer F, Boehm S, Freissmuth M, Sitte HH.
A Quantitative Model of Amphetamine Action on the Serotonin Transporter.
Br J Pharmacol. 2014 Feb;171(4):1007-18. doi: 10.1111/bph.12520.
Savalli G, Diao W, Schulz S, Todtova K, Pollak DD.
Diurnal oscillation of amygdala clock gene expression and loss of synchrony in a mouse model of depression.
Int J Neuropsychopharmacol. 2014 Dec 11;18(5). pii: pyu095. doi: 10.1093/ijnp/pyu095.
Scharinger C, Rabl U, Kasess CH, Meyer BM, Hofmaier T, Diers K, Bartova L, Pail G, Huf W, Uzelac Z, Hartiner B, Kalcher K, Perkmann T, Haslacher H, Meyer-Lindenberg A, Kasper S, Freissmuth M, Windischberger C, Willeit M, Lanzenberger R, Esterbauer H, Brocke B, Moser E, Sitte HH, Pezawas L.
Platelet serotonin transporter function predicts default-mode network activity.
PLoS One. 2014 Mar 25;9(3):e92543. doi: 10.1371/journal.pone.0092543.
Steinkellner T, Mus L, Eisenrauch B, Constantinescu A, Leo D, Konrad L, Rickhag M, Sørensen G, Efimova EV, Kong E, Willeit M, Sotnikova TD, Kudlacek O, Gether U, Freissmuth M, Pollak DD, Gainetdinov RR, Sitte HH.
In vivo Amphetamine Action is Contingent on αCaMKII.
Neuropsychopharmacology. 2014 Oct;39(11):2681-93. doi: 10.1038/npp.2014.124.
Viereck M, Gaulton A, Digles D, Ecker GF,
Transporter taxonomy – a comparison of different transport protein classification schemes.
Drug Discov Today Technol. 2014 Jun;12:e37-46. doi: 10.1016/j.ddtec.2014.03.004.
Woolbright BL, Li F, Xie Y, Farhood A, Fickert P, Trauner M, Jaeschke H.,
Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice.
Toxicol Lett. 2014 Jul 3;228(1):56-66. doi: 10.1016/j.toxlet.2014.04.001.
Zdrazil B, Chichester C, Zander Balderud L, Engkvist O, Gaulton A, Overington JP,
Transporter assays and assay ontologies: useful tools for drug discovery.
Drug Discov Today Technol. 2014 Jun;12:e47-54. doi: 10.1016/j.ddtec.2014.03.005.
Zhang J, Chtcheglova LA, Zhu R, Hinterdorfer P, Tang J, Zhang B,
Nano-scale Organization of Human GnRH-R on Human Bladder Cancer Cells.
Anal Chem. 2014 Mar 4;86(5):2458-64. doi: 10.1021/ac403304g.
Reviews/book chapters 2014
Baghdasaryan A, Chiba P, Trauner M.
Clinical application of transcriptional activators of bile salt transporters.
Mol Aspects Med. 2014 Jun;37:57-76. doi: 10.1016/j.mam.2013.12.001. Review
Bankstahl JP,
What does a picture tell? In vivo imaging of ABC transporter function.
Drug Discov Today Technol. 2014 Jun;12:e113-9. doi: 10.1016/j.ddtec.2014.03.014.
Chiba P, Freissmuth M, Stockner T.
Defining the blanks – Pharmacochaperoning of SLC6 transporters and ABC transporters.
Pharmacol Res. 2014 May;83:63-73. doi: 10.1016/j.phrs.2013.11.009.
Cuperus FJC, Claudel T, Gautherot J, Halilbasic E, Trauner M.
The role of canalicular ABC transporters in cholestasis.
Drug Metab Dispos. 2014 Apr;42(4):546-60. doi: 10.1124/dmd.113.056358.
Fuchs CD, Claudel T, Trauner M.
Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD.
Trends Endocrinol Metab. 2014 Nov;25(11):576-85. doi: 10.1016/j.tem.2014.08.001.
Kong E, Monje FJ, Hirsch J, Pollak DD.
Learning not to Fear: Neural Correlates of Learned Safety.
Neuropsychopharmacology. 2014 Feb;39(3):515-27. doi: 10.1038/npp.2013.191.
Pinto M, Digles D, Ecker GF.
Computational Models for predicting the interaction with ABC-transporter.
Drug Discov Today Technol. 2014 Jun;12:e69-77. doi: 10.1016/j.ddtec.2014.03.007.
Schaap FG, Trauner M, Jansen PL.
Bile acid receptors as targets for drug development.
Nat Rev Gastroenterol Hepatol. 2014 Jan;11(1):55-67. doi: 10.1038/nrgastro.2013.151
Stieger B, Unadkat JD, Prasad B, Langer O, Gali H.
Role of (drug) transporters in imaging in health and disease.
Drug Metab Dispos. 2014 Dec;42(12):2007-15. doi: 10.1124/dmd.114.059873.
Stockner T, Jurik A, Weissensteiner R, Freissmuth M, Ecker GF, Sitte HH.
Development of refined homology models: Adding the missing information to the medically relevant neurotransmitter transporters.
In: "Membrane Transporter Mechanism: 3D structure and beyond", pp 99-120,
Springer Series in Biophysics: Transporters. Eds.: Krämer R., Ziegler C., 2014, ISBN 978-3-642-53839-1
Trauner M, Halilbasic E, Kazemi-Shirazi L, Kienbacher C, Staufer K, Traussnigg S, Hofer H.
Therapeutic role of bile acids and nuclear receptor agonists in fibrosing cholangiopathies.
Dig Dis. 2014;32(5):631-6. doi: 10.1159/000360517.
Wulkersdorfer B, Wanek T, Bauer M, Zeitlinger M, Müller M, Langer O.
Using positron emission tomography to study transporter-mediated drug-drug interactions in tissues.
Clinical Pharmacology and Therapeutics, Clin Pharmacol Ther. 2014 Aug;96(2):206-13. doi: 10.1038/clpt.2014.70.
Zhu R, Duman M, Madl J, Schütz GJ, Hinterdorfer P.
Combined Topography, Recognition, and Fluorescence Measurements on Cells;
Cell Membrane Nanodomains: from Biochemistry to Nanoscopy, Chapter 16, Pages 367-390,
CRC Press 2014, Print ISBN: 978-1-4822-0989-1, eBook ISBN: 978-1-4822-0991-4, doi: 10.1201/b17634-21
Original papers 2013
Bankstahl JP, Bankstahl M, Römermann K, Wanek T, Stanek J, Windhorst AD, Fedrowitz M, Erker T, Müller M, Löscher W, Langer O, Kuntner C,
Tariquidar and elacridar are dose-dependently transported by P-glycoprotein and Bcrp at the blood-brain barrier: a small-animal positron emission tomography and in vitro study.
Drug Metab Dispos. 2013 Apr;41(4):754-62. doi: 10.1124/dmd.112.049148
Bauer M, Karch R, Zeitlinger M, Stanek J, Philippe C, Wadsak W, Markus Mitterhauser, Walter Jäger, Helmuth Haslacher, Müller M, Langer O.
Interaction of 11C-tariquidar and 11C-elacridar with P-glycoprotein and breast cancer resistance protein at the human blood-brain barrier.
J Nucl Med. 2013 Aug;54(8):1181-7. doi: 10.2967/jnumed.112.118232
Bauer M, Zeitlinger M, Todorut D, Böhmdorfer M, Müller M, Langer O, Jäger W.
Pharmacokinetics of single ascending doses of the P-glycoprotein inhibitor tariquidar in healthy subjects.
Pharmacology, 2013;91(1-2):12-9. doi: 10.1159/000343243
Baumann MH, Partilla JS, Lehner KR, Throndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW
Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive 'Bath Salts' Products.
Neuropsychopharmacology. 2013 Mar;38(4):552-62. doi: 10.1038/npp.2012.204. Epub 2012 Oct 17.
Buchmayer F, Schicker K, Steinkellner T, Geier P, Stübiger G, Hamilton PJ, Jurik A, Stockner T, Yang JW, Montgomery T, Holy M, Hofmaier T, Kudlacek O, Matthies HJ, Ecker GF, Bochkov V, Galli A, Boehm S, Sitte HH.
Amphetamine actions at the serotonin transporter rely on the availability of phosphatidylinositol-4,5-bisphosphate.
Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11642-7. doi: 10.1073/pnas.1220552110
Cozzi NV, Brandt SD, Daley PF, Partilla JS, Rothman RB, Tulzer A, Sitte HH, Baumann MH.
Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs.
Eur J Pharmacol 2013 Jan 15;699(1-3): 180-7. doi: 10.1016/j.ejphar.2012.11.008 Epub 2012 Nov. 21
Duman M, Chtcheglova LA, Zhu R, Bozna BL, Polzella P, Cerundolo V, Hinterdorfer P.
Nanomapping of CD1d–glycolipid complexes on THP1 cells by using simultaneous topography and recognition imaging.
J Mol Recognit, 2013 Sep;26(9):408-14. doi: 10.1002/jmr.2282
Fickert P, Krones E, Pollheimer MJ, Thueringer A, Moustafa T, Silbert D, Halilbasic E, Yang M, Jaeschke H, Stokman G, Wells RG, Eller K, Rosenkranz AR, Eggertsen G, Wagner CA, Langner C, Denk H, Trauner M.
Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice.
Hepatology, 2013 Dec;58(6):2056-69. doi: 10.1002/hep.26599
Fickert P, Pollheimer MJ, Silbert D, Moustafa T, Halilbasic E, Krones E, Durchschein F, Thüringer A, Zollner G, Denk H, Trauner M.
Differential effects of norUDCA and UDCA in obstructive cholestasis in mice.
J Hepatol 2013 Jun;58(6):1201-8. doi: 10.1016/j.jhep.2013.01.026
Jabeen I, Wetwitayaklung P, Chiba P, Pastor M, Ecker GF.
2D- and 3D-QSAR studies of a series of benzopyranes and benzopyrano[3,4b][1,4]-oxazines as inhibitors of the multidrug transporter P-glycoprotein.
J Comput Aided Mol Des. 2013 Feb;27(2):161-71. doi: 10.1007/s10822-013-9635-9
Jurik A, Reicherstorfer R, Zdrazil B, Ecker GF.
Classification of High-Activity Tiagabine Analogs by Binary QSAR Modeling.
Mol Inform. 2013 Jun;32(5-6):415-419
Kannan P, Pike VW, Halldin C, Langer O, Gottesman MM, Innis RB, Hall MD.
Factors that limit positron emission tomography imaging of p-glycoprotein density at the blood-brain barrier.
Mol Pharm 2013 Jun 3;10(6):2222-9. doi: 10.1021/mp400011g
Marzioni M, Saccomanno S, Agostinelli L, Rychlicki C, De Minicis S, Pierantonelli I, Trauner M, Fickert P, Müller T, Shanmukhappa K, Trozzi L, Candelaresi C, Baroni GS, Benedetti A.
PDX-1/Hes-1 interactions determine cholangiocyte proliferative response to injury in rodents: possible implications for sclerosing cholangitis.
J Hepatol. 2013 Apr;58(4):750-6. doi: 10.1016/j.jhep.2012.11.033
Monje FJ, Divisch I, Demit M, Lubec G, Pollak DD.
Flotillin-1 is an evolutionary-conserved memory-related protein up-regulated in implicit and explicit learning paradigms.
Ann Med. 2013 Jun;45(4):301-7. doi: 10.3109/07853890.2013.77063
Moritz AE, Foster JD, Gorentla BK, Mazei-Robison MS, Yang JW, Sitte HH, Blakely RD, Vaughan RA.
Phosphorylation of dopamine transporter serine 7 modulates cocaine analog binding.
J Biol Chem. 2013 Jan 4;288(1):20-32. doi: 10.1074/jbc.M112.407874 Epub 2012 Nov. 16
Müllauer J, Karch R, Bankstahl JP, Bankstahl M, Stanek J, Wanek T, Mairinger S, Müller M, Löscher W, Langer O, Kuntner C.
Assessment of cerebral P-glycoprotein expression and function with PET by combined [11C]inhibitor and [11C]substrate scans in rats.
Nucl Med Biol. 2013 Aug;40(6):755-63. doi: 10.1016/j.nucmedbio.2013.05.005
Müllauer J, Willimayer R, Goertzen AL, Wanek T, Langer O, Birkfellner W, Kuntner C,
18F, 11C and 68Ga in small animal PET imaging. Evaluation of partial volume correction methods.
Nuklearmedizin. 2013 Dec 13;52(6):250-61. doi: 10.3413/Nukmed-0578-13-04
Rainer PP, Primessnig U, Harenkamp S, Doleschal B, Wallner M, Fauler G, Stojakovic T, Wachter R, Yates A, Groschner K, Trauner M, Pieske BM, von Lewinski D,
Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.
Heart. 2013 Nov;99(22):1685-92. doi: 10.1136/heartjnl-2013-304163
Römermann K, Wanek T, Bankstahl M, Bankstahl JP, Fedrowitz M, Müller M, Löscher W, Kuntner C, Langer O.
(R)-[(11)C]verapamil is selectively transported by murine and human P-glycoprotein at the blood-brain barrier, and not by MRP1 and BCRP.
Nucl Med Biol. 2013 Oct;40(7):873-8. doi: 10.1016/j.nucmedbio.2013.05.012
Rosenauer R, Luf A, Holy M, Freissmuth M, Schmid R, Sitte HH,
A combined approach using transporter-flux assays and mass spectrometry to examine psychostimulant street drugs of unknown content.
ACS Chem Neurosci. 2013 Jan 16;4(1):182-90. doi: 10.1021/cn3001763
Seddik A, Holy M, Weissensteiner R, Zdrazil B, Sitte HH, Ecker GF.
Probing the Selectivity of Monoamine Transporter Substrates by Means of Molecular Modeling.
Mol Inform. 2013 Jun;32(5-6):409-413
Stockner T, Montgomery TR, Kudlacek O, Weissensteiner R, Ecker GF, Freissmuth M, Sitte HH.
Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model.
PLoS Comput Biol. 2013;9(2):e1002909. doi: 10.1371/journal.pcbi.1002909
Sucic S, Koban F, El-Kasaby A, Kudlacek O, Stockner T, Sitte HH, Freissmuth M.
Switching the clientele: a lysine residing in the C terminus of the serotonin transporter specifies its preference for the coat protein complex II component SEC24C.
J Biol Chem. 2013 Feb 22;288(8):5330-41. doi: 10.1074/jbc.M112.408237
Wanek T, Mairinger S, Langer O.
Radioligands targeting P-glycoprotein and other drug efflux proteins at the blood-brain barrier. Special issue: Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with PET.
J Labelled Comp Radiopharm. 2013 Mar-Apr;56(3-4):68-77. doi: 10.1002/jlcr.2993
Werner M, Atil B, Sieczkowski E, Chiba P, Hohenegger M.
Simvastatin-induced compartmentalisation of doxorubicin sharpens up nuclear topoisomerase II inhibition in human rhabdomyosarcoma cells.
Naunyn Schmiedebergs Arch Pharmacol. 2013 Jul;386(7):605-17. doi: 10.1007/s00210-013-0859-y
Zhang J, Liu H, Zhu R, Hinterdorfer P, Zhang B, Tang J.
Single molecular dissection of the ligand binding property of epidermal growth factor receptor.
Analyst. 2013 Sep 21;138(18):5325-31. doi: 10.1039/c3an00778b
Zhu R, Rupprecht A, Ebner A, Haselgrübler T, Gruber HJ, Hinterdorfer P, Pohl EE.
Mapping the nucleotide binding site of uncoupling protein 1 using atomic force microscopy.
J Am Chem Soc. 2013 Mar 6;135(9):3640-6. doi: 10.1021/ja312550k
Reviews/book chapters 2013
Claudel T, Trauner M.
Adiponectin, bile acids, and burnt-out nonalcoholic steatohepatitis: new light on an old paradox.
Hepatology. 2013 Jun;57(6):2106-9. doi: 10.1002/hep.26340
Fuchs C, Claudel T, Trauner M.
Bile acid-mediated control of liver triglycerides.
Semin Liver Dis. 2013 Nov;33(4):330-42. doi: 10.1055/s-0033-1358520.
Halilbasic E, Baghdasaryan A, Trauner M.
Nuclear receptors as drug targets in cholestatic liver diseases.
Clin Liver Dis. 2013 May;17(2):161-89. doi: 10.1016/j.cld.2012.12.001.
Halilbasic E, Claudel T, Trauner M.
Bile acid transporters and regulatory nuclear receptors in the liver and beyond.
J Hepatol. 2013 Jan;58(1):155-68. doi: 10.1016/j.jhep.2012.08.002. review
Müller M
Introduction to the Microdialysis Technology.
In "Microdialysis in Drug Development", Editor: Müller M. Series: AAPS Advances in the Pharmaceutical Sciences Series Vol. 4.
Springer-Verlag New York (2013) doi: 10.1007/978-1-4614-4815-0,
ISBN 978-1-4614-4815-0, eBook ISBN 978-1-4614-4815-0
Pezawas L, Santos A, Meyer-Lindenberg A.
Genetics and Emotion.
In: "The Oxford Handbook of Cognitive Neuroscience, Volume 2: The Cutting Edges" Editors: Ochnsern K, Kosslyn SM.
Oxford University Press (2013), doi: 10.1093/oxfordhb/9780199988709.013.0006,
ISBN-10: 0199988706, ISBN-13: 9780199988709
Original papers 2012
Bauer M, Zeitlinger M, Karch R, Matzneller P, Stanek J, Jäger W, Böhmdorfer M, Wadsak W, Mitterhauser M, Bankstahl JP, Löscher W, Koepp M, Müller M, Langer O.
Pgp-mediated interaction between (R)-[11C]verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data.
Clin Pharmacol Ther. 2012 Feb;91(2):227-33. doi: 10.1038/clpt.2011.217
Bauer F, Wanek T, Mairinger S, Stanek J, Sauberer M, Kuntner C, Parveen Z, Chiba P, Müller M, Langer O, Erker T.
Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography.
Eur J Pharmacol. 2012 Dec 5;696(1-3):18-27. doi: 10.1016/j.ejphar.2012.09.013
Boubela RN, Huf W, Kalcher K, Sladky R, Filzmoser P, Pezawas L, Kasper S, Windischberger C, Moser E.
A highly parallelized framework for computationally intensive MR data analysis.
MAGMA. 2012 Aug;25(4):313-20. doi: 10.1007/s10334-011-0290-7
Brast S, Grabner A, Sucic S, Sitte HH, Hermann E, Pavenstädt H, Schlatter E, Ciarimboli G.
The cysteines of the extracellular loop are crucial for trafficking of human organic cation transporter 2 to the plasma membrane and are involved in oligomerization.
FASEB J. 2012 Mar;26(3):976-86. doi: 10.1096/fj.11-180679
Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber C, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W.
The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters.
J Biol Chem. 2012 May 25;287(22):18524-34. doi: 10.1074/jbc.M112.343681
Foster JD, Yang JW, Moritz AE, Challasivakanaka S, Smith MA, Holy M, Wilebski K, Sitte HH, Vaughan RA.
Dopamine transporter phosphorylation site threonine 53 regulates substrate reuptake and amphetamine-stimulated efflux.
J Biol Chem 2012 Aug 24;287(35):29702-12. doi: 10.1074/jbc.M112.367706
Jabeen I, Pleban K, Rinner U, Chiba P, Ecker GF.
Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein.
J Med Chem. 2012 Apr 12;55(7):3261-73. doi: 10.1021/jm201705f
Kalcher K, Huf W, Boubela RN, Filzmoser P, Pezawas L, Biswal B, Kasper S, Moser E, Windischberger C.
Fully exploratory network independent component analysis of the 1000 functional connectomes database.
Front Hum Neurosci. 2012 Nov 6;6:301. doi: 10.3389/fnhum.2012.00301
Mairinger S, Bankstahl JP, Kuntner C, Römermann K, Bankstahl M, Wanek T, Stanek J, Löscher W, Müller M, Erker T, Langer O.
The antiepileptic drug mephobarbital is not transported by P-glycoprotein or multidrug resistance protein 1 at the blood-brain barrier: a positron emission tomography study.
Epilepsy Res 2012 Jun;100(1-2):93-103. doi: 10.1016/j.eplepsyres.2012.01.012
Mairinger S, Wanek T, Kuntner C, Doenmez Y, Strommer S, Stanek J, Capparelli E, Chiba P, Müller M, Colabufo NA, Langer O.
Synthesis and preclinical evaluation of the radiolabeled P-glycoprotein inhibitor [11C]MC113.
Nucl Med Biol 2012 Nov;39(8):1219-25. doi: 10.1016/j.nucmedbio.2012.08.005
Müllauer J, Kuntner C, Bauer M, Jens P, Bankstahl, Müller M, Langer O, Syvänen S.
Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood-brain barriers studied with (R)-[11C]verapamil positron emission tomography.
EJNMMI Res. 2012 Oct 16;2(1):58. doi: 10.1186/2191-219X-2-58
Pinto M, Trauner M, Ecker GF.
An In Silico Classification Model for Putative ABCC2 Substrates.
Mol Inform 2012 Aug;31(8):547-553
Poongavanam V, Haider N, Ecker GF.
Fingerprint-based in silico models for the prediction of P-glycoprotein substrates and inhibitors.
Bioorg Med Chem 2012 Sep 15;20(18):5388-95. doi: 10.1016/j.bmc.2012.03.045
Schicker K, Uzelac Z, Gesmonde J, Bulling S, Stockner T, Freissmuth M, Boehm S, Rudnick G, Sitte HH, Sandtner W.
Unifying concept of serotonin transporter-associated currents.
J Biol Chem. 2012 Jan 2;287(1):438-45. doi: 10.1074/jbc.M111.304261
Sieben C, Kappel C, Zhu R, Wozniak A, Rankl C, Hinterdorfer P, Grubmüller H, Herrmann A.
Influenza virus binds its host cell using multiple dynamic interactions.
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13626-31. doi: 10.1073/pnas.1120265109
Steinkellner T, Yang JW, Montgomery TR, Chen WQ, Winkler MT, Sucic S, Lubec G, Freissmuth M, Elgersma Y, Sitte HH, Kudlacek O.
Ca(2+)/calmodulin-dependent protein kinase IIα (αCaMKII) controls the activity of the dopamine transporter: implications for Angelman syndrome.
J Biol Chem. 2012 Aug 24;287(35):29627-35. doi: 10.1074/jbc.M112.367219
Wanek T, Kuntner C, Bankstahl JP, Mairinger S, Bankstahl M, Stanek J, Sauberer M, Filip T, Erker T, Müller M, Löscher W, Langer O.
A novel PET protocol for visualization of breast cancer resistance protein function at the blood-brain barrier.
J Cereb Blood Flow Metab 2012 Nov;32(11):2002-11. doi: 10.1038/jcbfm.2012.112
Wanek T, Kuntner C, Bankstahl JP, Bankstahl M, Stanek J, Sauberer M, Mairinger S, Strommer S, Wacheck V, Löscher W, Erker T, Müller M, Langer O.
A comparative small-animal PET evaluation of [(11)C]tariquidar, [ (11)C]elacridar and (R)-[(11)C]verapamil for detection of P-glycoprotein-expressing murine breast cancer.
Eur J Nucl Med Mol Imaging. 2012 Jan;39(1):149-59. doi: 10.1007/s00259-011-1941-7
Wildling L, Rankl C, Haselgruebler T, Gruber HJ, Holy M, Newman AH, Zou MF, Zhu R, Freissmuth M, Sitte HH, Hinterdorfer P.
Probing the binding pocket of the serotonin transporter by single molecular force spectroscopy on living cells.
J Biol Chem. 2012 Jan 2;287(1):105-13. doi: 10.1074/jbc.M111.304873
Reviews/book chapters 2012
Jurik A, Klepsch F, Zdrazil B.
Molecular Modeling and Simulation of Membrane Transport Proteins.
In "Medicinal Chemistry and Drug Design" Edited: Deniz Ekinci.
InTech under CC BY 3.0 license (2012), doi: 10.5772/2457, ISBN 978-953-51-0513-8
Weissensteiner R, Steinkellner T, Jurik A, Bulling S, Sandtner W, Kudlacek O, Freissmuth M, Ecker GF, Sitte HH.
Towards an understanding of the psychostimulant action of amphetamine and cocaine.
In: "Sensory Perception: Mind and Matter", pp183-203, Editors: Barth FG, Giamperi-Deutsch P, Klein HD.
Springer Verlag Vienna (2012), doi: 10.1007/978-3-211-99751-2, ISBN: 978-3-211-99750-5 (Print) 978-3-211-99751-2 (Online)
Original papers 2011
Bankstahl JP, Bankstahl M, Kuntner C, Stanek J, Wanek T, Meier M, Ding X-Q, Müller M, Langer O, Löscher W.
A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.
J Neurosci. 2011 Jun 15;31(24):8803-11. doi: 10.1523/JNEUROSCI.6616-10.2011
Borecká S, Pinjon E, Sullivan DJ, Kuchler K, Blaško J, Kulková N, Bujdáková H.
Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.
Can J Microbiol. 2011 May;57(5):416-26. doi: 10.1139/W11-025
Dörner B, Kuntner C, Bankstahl JP, Wanek T, Bankstahl M, Stanek J, Müllauer J, Bauer F, Mairinger S, Löscher W, Miller DW, Chiba P, Müller M, Erker T, Langer O.
Radiosynthesis and in vivo evaluation of 1-[(18)F]fluoroelacridar as a positron emission tomography tracer for P-glycoprotein and breast cancer resistance protein.
Bioorg Med Chem. 2011 Apr 1;19(7):2190-8. doi: 10.1016/j.bmc.2011.02.039
Jabeen I, Wetwitayaklung P, Klepsch F, Parveen Z, Chiba P, Ecker GF.
Probing the stereoselectivity of P-glycoprotein – synthesis, biological activity and preliminary docking studies of a set of enantiopure benzopyrano[3,4b][1,4]oxazines.
Chem Commun (Camb). 2011 Mar 7;47(9):2586-8. doi: 10.1039/c0cc03075a
Keller T, Egenberger B, Gorboulev V, Bernhard F, Uzelac Z, Gorbunov D, Wirth C, Koppatz S, Dötsch V, Hunte C, Sitte HH, Koepsell H.
The large extracellular loop of organic cation transporter 1 influences substrate affinity and is pivotal for oligomerization.
J Biol Chem. 2011 Oct 28;286(43):37874-86. doi: 10.1074/jbc.M111.289330
Klepsch F, Chiba P, Ecker GF.
Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein.
PLoS Comp Biol. 2011 May;7(5):e1002036. doi: 10.1371/journal.pcbi.1002036
Malle E, Zhou H, Neuhold J, Spitzenberger B, Klepsch F, Pollak T, Bergner O, Ecker GF, Stolt-Bergner PC.
Random mutagenesis of the prokaryotic peptide transporter YDGR identifies potential periplasmic gating residues.
J Biol Chem. 2011 Jul 1;286(26):23121-31. doi: 10.1074/jbc.M111.239657
Navaroli DM, Stevens ZH, Uzelac Z, Gabriel L, King MJ, Lifshitz LM, Sitte HH, Melikian HE.
The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking.
J Neurosci. 2011 Sep 28;31(39):13758-70. doi: 10.1523/JNEUROSCI.2649-11.2011
Parveen Z, Stockner T, Bentele C, Pferschy S, Kraupp M, Freissmuth M, Ecker GF, Chiba P.
Molecular dissection of dual pseudosymmetric solute translocation pathways in human P-glycoprotein.
Mol Pharmacol. 2011 Mar;79(3):443-52. doi: 10.1124/mol.110.067611
Sucic S, El-Kasaby A, Kudlacek O, Sarker S, Sitte HH, Marin P, Freissmuth M.
The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C.
J Biol Chem. 2011 May 6;286(18):16482-90. doi: 10.1074/jbc.M111.230037
Wagner CC, Simpson M, Zeitlinger M, Bauer M, Karch R, Abrahim A, Feurstein T, Schütz M, Kletter K, Müller M, Lappin G, Langer O
A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.
Clin Pharmacokinet. 2011 Feb;50(2):111-20. doi: 10.2165/11537250-000000000-00000
Wildling L, Unterauer B, Zhu R, Rupprecht A, Haselgrübler T, Rankl C, Ebner A, Vater D, Pollheimer P, Pohl EE, Hinterdorfer P, Gruber HJ.
Linking of sensor molecules with amino groups to amino-functionalized AFM tips.
Bioconjug Chem. 2011 Jun 15;22(6):1239-48. doi: 10.1021/bc200099t
Reviews/book chapters 2011
Klein C, Kuchler K, Valachovic M.
ABC proteins in yeast & fungal pathogens.
Essays Biochem. 2011 Sep 7;50(1):101-19. doi: 10.1042/bse0500101, review
Kuchler K.
The ABC of ABCs: multidrug resistance and genetic diseases.
FEBS J. 2011 Sep;278(18):3189. doi: 10.1111/j.1742-4658.2011.08234.x
Mairinger S, Erker T, Muller M, Langer O.
PET and SPECT radiotracers to assess function and expression of ABC transporters in vivo.
Curr Drug Metab. 2011 Oct;12(8):774-92. Review.
Rabl U, Scharinger C, Hofmaier T, Freissmuth M, Pezawas L.
Genetic regulation of emotion brain circuitries.
In: "Neurobiology of Depression" pp 75-95 Editors: López-Muñoz F, Álamo C.
CRC Press (2011) doi: 10.1201/b11232-5,
ISBN 978-1-4398-3849-5, eBook ISBN: 978-1-4398-3850-1
Scharinger C, Bartova L, Pezawas L.
Brain-derived neurotrophic factor: a peripheral biomarker for major depressive disorder and antidepressant efficacy?
Personalized Medicine March 2011 ,Vol. 8, No. 2, Pages 115-117 , doi:10.2217/pme.11.9
Scharinger C, Rabl U, Pezawas L, Kasper S.
The genetic blueprint of Major Depressive Disorder: contributions of imaging genetics studies.
World J Biol Psychiatry. 2011 Oct;12(7):474-88. doi: 10.3109/15622975.2011.596220.
Steinkellner T, Freissmuth M, Sitte HH, Montgomery T.
The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine.
Biol Chem. 2011 Jan;392(1-2):103-15. doi: 10.1515/BC.2011.016
Tscherner M., Schwarzmüller T, Kuchler K.
Pathogenesis and Antifungal Drug Resistance of the Human Fungal Pathogen Candida glabrata.
Pharmaceuticals (Basel). 2011 Jan; 4(1): 169–186, doi: 10.3390/ph4010169
Wagner CC, Langer O.
Approaches using molecular imaging technology - use of PET in clinical microdose studies.
Adv Drug Deliv Rev. 2011 Jun 19;63(7):539-46. doi: 10.1016/j.addr.2010.09.011 Review
Original papers 2010
Assem-Hilger E, Lanzenberger R, Savli M, Wadsak W, Mitterhauser M, Mien LK, Stögmann E, Baumgartner C, Kletter K, Asenbaum S.
Central serotonin 1A receptor binding in temporal lobe epilepsy: a [carbonyl-(11)C]WAY-100635 PET study.
Epilepsy Behav. 2010 Nov;19(3):467-73. doi: 10.1016/j.yebeh.2010.07.030
Bauer F, Kuntner C, Bankstahl JP, Wanek T, Bankstahl M, Stanek J, Mairinger S, Dörner B, Löscher W, Müller M, Erker T, Langer O.
Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor.
Bioorg Med Chem. 2010 Aug 1;18(15):5489-97. doi: 10.1016/j.bmc.2010.06.057
Bauer M, Karch R, Neumann F, Wagner CC, Kletter K, Müller M, Löscher W, Zeitlinger M, Langer O.
Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.
J Cereb Blood Flow Metab. 2010 Mar;30(3):510-5. doi: 10.1038/jcbfm.2009.265
Demel MA, Kraemer O, Ettmayer P, Haaksma E, Ecker GF.
Ensemble Rule-based classification of substrates of the human ABC-transporter ABCB1 using simple physicochemical descriptors.
Mol Inform. 2010 Mar 15;29(3):233-42. doi: 10.1002/minf.200900079
El-Kasaby A, Just H, Malle E, Stolt-Bergner PC, Sitte HH, Freissmuth M, Kudlacek O.
Mutations in the carboxyl-terminal SEC24 motif of the serotonin transporter impair folding of the transporter.
J Biol Chem. 2010 Dec 10;285(50):39201-10. doi: 10.1074/jbc.M110.118000
Ernst R, Kueppers P, Stindt J, Kuchler K, Schmitt L.
Multidrug efflux pumps: substrate selection in ATP-binding cassette multidrug efflux pumps--first come, first served?
FEBS J. 2010 Feb;277(3):540-9. doi: 10.1111/j.1742-4658.2009.07485.x
Frohner IE, Gregori C, Anrather D, Roitinger E, Schüller C, Ammerer G, Kuchler K.
Weak organic acid stress triggers hyperphosphorylation of the yeast zinc-finger transcription factor War1 and dampens stress adaptation.
OMICS. 2010 Oct;14(5):575-86. doi: 10.1089/omi.2010.0032
Janneh O, Bray PG, Jones E, Wyen C, Chiba P, Back DJ, Khoo SH.
Concentration-dependent effects and intracellular accumulation of HIV protease inhibitors in cultured CD4 T cells and primary human lymphocytes.
J Antimicrob Chemother. 2010 May;65(5):906-16. doi: 10.1093/jac/dkq082
Kasess CH, Stephan KE, Weissenbacher A, Pezawas L, Moser E, Windischberger C.
Multi-subject analyses with dynamic causal modeling.
Neuroimage. 2010 Feb 15;49(4):3065-74. doi: 10.1016/j.neuroimage.2009.11.037
Kienberger F, Zhu R, Rankl C, Gruber HJ, Blaas D, Hinterdorfer P.
Atomic force microscopy studies of human rhinovirus topology and molecular forces.
Methods Enzymol. 2010;475:515-39. doi: 10.1016/S0076-6879(10)75019-9.
Kohut P, Wüstner D, Hronska L, Kuchler K, Hapala I, Valachovic M.
The role of the ABC proteins Aus1 and Pdr11 in the uptake of external cholesterol in yeast: a dehydroergosterol fluourescence study.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):233-8. doi: 10.1016/j.bbrc.2010.11.099
Kuntner C, Bankstahl JP, Bankstahl M, Stanek J, Wanek T, Stundner G, Karch R, Brauner R, Meier M, Ding X, Müller M, Löscher W, Langer O.
Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[(11)C]verapamil PET.
Eur J Nucl Med Mol Imaging. 2010 May;37(5):942-53. doi: 10.1007/s00259-009-1332-5
Mairinger S, Langer O, Kuntner C, Wanek T, Bankstahl JP, Bankstahl M, Stanek J, Dörner B, Bauer F, Baumgartner C, Löscher W, Erker T, Müller M.
Synthesis and in vivo evaluation of the putative breast cancer resistance protein inhibitor [11C]methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl)phenyl)amino-carbonyl)-2-(quinoline-2-carbonylamino)benzoate.
Nucl Med Biol. 2010 Jul;37(5):637-44. doi: 10.1016/j.nucmedbio.2010.02.008
Sarker S, Weissensteiner R, Steiner I, Sitte HH, Ecker GF, Freissmuth M, Sucic S.
The high-affinity binding site for tricyclic antidepressants resides in the outer vestibule of the serotonin transporter.
Mol Pharmacol. 2010 Dec;78(6):1026-35. doi: 10.1124/mol.110.067538
Sucic S, Dallinger S, Zdrazil B, Weissensteiner R, Jorgensen TN, Holy M, Kudlacek O, Seidel S, Cha JH, Gether U, Newman AH, Ecker GF, Freissmuth M, Sitte HH.
The N terminus of monoamine transporters is a lever required for the action of amphetamines.
J Biol Chem. 2010 Apr 2;285(14):10924-38. doi: 10.1074/jbc.M109.08315
Zhu R, Howorka S, Pröll J, Kienberger F, Preiner J, Hesse J, Ebner A, Pastushenko VP, Gruber HJ, Hinterdorfer P.
Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns.
Nat Nanotechnol. 2010 Nov; 5(11):788-91. doi: 10.1038/nnano.2010.212 Epub 2010 Oct. 31.
Reviews/book chapters 2010
Bartova L, Berger A, Pezawas L.
Is there a personalized medicine for mood disorders?
Eur Arch Psychiatry Clin Neurosci. 2010 Nov;260 Suppl 2:S121-6. doi: 10.1007/s00406-010-0152-8
Klepsch F, Jabeen I, Chiba P, Ecker GF.
Pharmacoinformatic approaches to design natural product type ligands of ABC-transporters.
Curr Pharm Des. 2010 May;16(15):1742-52, review
Klepsch F, Ecker GF.
Impact of the recent mouse P-glycoprotein structure for structure-based ligand design.
Mol Inform. 2010 Apr 12;29(4):276-86. doi: 10.1002/minf.201000017. Review
Klepsch F, Stockner T, Erker T, Müller M, Chiba P, Ecker GF.
Using structural and mechanistic information to design novel inhibitors/substrates of P-glycoprotein.
Curr Top Med Chem. 2010;10(17):1769-74 Review
Löscher W, Langer O.
Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy.
Curr Top Med Chem. 2010;10(17):1785-91. Review.
Pezawas L, Meyer-Lindenberg A.
Imaging genetics: Progressing by leaps and bounds.
Neuroimage. 2010 Nov 15;53(3):801-3. doi: 10.1016/j.neuroimage.2010.08.001
Rabl U, Hartinger B, Pezawas L.
At a glance: The serotonin reuptake speed regulates the activity of cingulate cortex.
Journal für Neurologie, Neurochirurgie und Psychiatrie 2010; 11 (3): 84
Rabl U, Scharinger C, Müller M, Pezawas L.
Imaging genetics: Implications for research on variable antidepressant drug response.
Expert Rev Clin Pharmacol. 2010 Jul;3(4):471-89. doi: 10.1586/ecp.10.35
Scharinger C, Rabl U, Sitte HH, Pezawas L.
Imaging genetics of mood disorders.
Neuroimage. 2010 Nov 15;53(3):810-21. doi: 10.1016/j.neuroimage.2010.02.019
Sitte HH, Freissmuth M.
The reverse operation of Na(+)/Cl(-)-coupled neurotransmitter transporters--why amphetamines take two to tango.
J Neurochem. 2010 Jan;112(2):340-55. doi: 10.1111/j.1471-4159.2009.06474.x
Original papers 2009
Bankstahl JP, Kuntner C, Abrahim A, Karch R, Stanek J, Wanek T, Wadsak W, Kletter K, Müller M, Löscher W, Langer O.
Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.
J Nucl Med. 2008 Aug;49(8):1328-35. doi: 10.2967/jnumed.108.051235
Bauer M, Karch R, Neumann F, Abrahim A, Wagner CC, Kletter K, Müller M, Zeitlinger M, Langer O.
Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET.
Eur J Clin Pharmacol. 2009 Sep;65(9):941-6. doi: 10.1007/s00228-009-0709-5
Dörner B, Kuntner C, Bankstahl JP, Bankstahl M, Stanek J, Wanek T, Stundner G, Mairinger S, Löscher W, Müller M, Langer O, Erker T.
Synthesis and small-animal positron emission tomography evaluation of [11C]-elacridar as a radiotracer to assess the distribution of P-glycoprotein at the blood-brain barrier.
J Med Chem. 2009 Oct 8;52(19):6073-82. doi: 10.1021/jm900940f
Egaña LA, Cuevas RA, Baust TB, Parra LA, Leak RK, Hochendoner S, Peña K, Quiroz M, Hong WC, Dorostkar MM, Janz R, Sitte HH, Torres GE.
Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3.
J Neurosci. 2009 Apr 8;29(14):4592-604. doi: 10.1523/JNEUROSCI.4559-08.2009
Maier S, Reiterer V, Ruggiero AM, Rothstein JD, Thomas S, Dahm R, Sitte HH, Farhan H.
GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation.
J Cell Mol Med. 2009 Jan;13(1):114-24. doi: 10.1111/j.1582-4934.2008.00303.x
Pirker S, Gasser E, Czech T, Baumgartner C, Schuh E, Feucht M, Novak K, Zimprich F, Sperk G.
Dynamic up-regulation of prodynorphin transcription in temporal lobe epilepsy.
Hippocampus. 2009 Nov;19(11):1051-4. doi: 10.1002/hipo.20633
Rockwell NC, Wolfger H, Kuchler K, Thorner J.
ABC transporter Pdr10 regulates the membrane microenvironment of Pdr12 in Saccharomyces cerevisiae.
J Membr Biol. 2009 May;229(1):27-52. doi: 10.1007/s00232-009-9173-5
Schlachter K, Gruber-Sedlmayr U, Stogmann E, Lausecker M, Hotzy C, Balzar J, Schuh E, Baumgartner C, Mueller JC, Illig T, Wichmann HE, Lichtner P, Meitinger T, Strom TM, Zimprich A, Zimprich F.
A splice site variant in the sodium channel gene SCN1A confers risk of febrile seizures.
Neurology. 2009 Mar 17;72(11):974-8. doi: 10.1212/01.wnl.0000344401.02915.00
Stockner T, de Vries SJ, Bonvin AM, Ecker GF, Chiba P.
Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains.
FEBS J. 2009 Feb;276(4):964-72. doi: 10.1111/j.1742-4658.2008.06832.x
Wagner CC, Bauer M, Karch R, Feurstein T, Kopp S, Chiba P, Kletter K, Löscher W, Müller M, Zeitlinger M, Langer O.
A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET.
J Nucl Med. 2009 Dec;50(12):1954-61. doi: 10.2967/jnumed.109.06328
Zhu R, Ebner A, Kastner M, Preiner J, Howorka S, Hinterdorfer P.
Topography and recognition imaging of protein-patterned surfaces generated by AFM nanolithography.
Chemphyschem. 2009 Jul 13; 10(9-10):1478-81. doi: 10.1002/cphc.200900245.
Reviews/book chapters 2009
Demel MA, Krämer O, Ettmayer P, Haaksma EEJ, Ecker GF.
Predicting ligand-interaction with ABC-transporters in ADME.
Chem Biodivers. 2009 Nov;6(11):1960-9. doi: 10.1002/cbdv.200900138
Ecker GF.
QSAR studies on ABC-transporter – how to deal with polyspecificity. In: Ecker GF, Chiba P (editors) “Transporters as Drug Carriers: Structure, Function, Substrates” from the series “Methods and Principles in Medicinal Chemistry”, pp197-214,
Wiley-VCH (2009) doi: 10.1002/9783527627424.ch7, Print ISBN: 9783527316618, Online ISBN: 9783527627424
Ecker GF, Chiba P.
ABC-transporters – from target to antitarget? In: Ecker GF, Chiba P (editors) “Transporters as Drug Carriers: Structure, Function, Substrates” from the series “Methods and Principles in Medicinal Chemistry”, pp 349-362,
Wiley-VCH, Weinheim (2009) doi: 10.1002/9783527627424.ch13, Print ISBN: 9783527316618, Online ISBN: 9783527627424
Pezawas L, Weinberger DR.
Molecular Genetics.
In: The International Encyclopedia of Depression. Editor: Ingram RI.
Springer Publishing Company, pp396-9. (2009) ISBN13: 9780826137937, EISBN: 9780826137944
Pezawas L, Meyer-Lindenberg A.
Genetically Driven Interactions in the Brain: Lessons from Depression.
Chapter 21, pp453-464 in: "Functional Pain Syndromes: Presentation and Pathophysiology". Editors: Mayer EA, Bushnell MC.
IASP Press (2009), ISBN13: 978-0931092756, ISBN-10: 0931092752
Schwarzmüller T, Klein C, Valachovic M, Glaser W, Kuchler K.
Membrane transporters in pleiotropic drug resistance and stress response in yeast and fungal pathogens.
In: Ecker GF, Chiba P (editors) “Transporters as Drug Carriers: Structure, Function, Substrates” from the series “Methods and Principles in Medicinal Chemistry”, pp159-194,
WILEY-VCH, Weinheim (2009) doi: 10.1002/9783527627424.ch6, Print ISBN: 9783527316618, Online ISBN: 9783527627424
Sitte HH, Freissmuth M.
GAT1.
UCSD Nature Molecule Pages Published online: 22 Jul 2009 | doi:10.1038/mp.a002759.01
Original papers 2008
Abrahim A, Luurtsema G, Bauer M, Karch R, Lubberink M, Pataraia E, Joukhadar C, Kletter K, Lammertsma AA, Baumgartner C, Müller M, Langer O.
Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients.
Eur J Nucl Med Mol Imaging. 2008 Jan;35(1):116-23
Bankstahl JP, Kuntner C, Abrahim A, Karch R, Stanek J, Wanek T, Wadsak W, Kletter K, Müller M, Löscher W, Langer O.
Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-[11C]verapamil and PET.
J Nucl Med. 2008 Aug;49(8):1328-35. doi: 10.2967/jnumed.108.051235
Ernst R, Kueppers P, Klein CM, Schwarzmueller T, Kuchler K, Schmitt L.
A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5.
Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5069-74. doi: 10.1073/pnas.0800191105
Gregori C, Schüller C, Frohner IE, Ammerer G, Kuchler K.
Weak organic acids trigger conformational changes of the yeast transcription factor War1 in vivo to elicit stress adaptation.
J Biol Chem. 2008 Sep 12;283(37):25752-64. doi: 10.1074/jbc.M803095200
Jungwirth H, Ring J, Mayer T, ,Schauer A., Büttner S., Eisenberg G, Carmona-Gutierrez D, Kuchler K, Madeo F.
Loss of peroxisome function triggers necrosis.
FEBS Lett. 2008 Aug 20;582(19):2882-6. doi: 10.1016/j.febslet.2008.07.023
Kasess CH, Windischberger C, Cunnington R, Lanzenberger R, Pezawas L, Moser E.
The suppressive influence of SMA on M1 in motor imagery revealed by fMRI and dynamic causal modeling.
Neuroimage. 2008 Apr 1;40(2):828-37. doi: 10.1016/j.neuroimage.2007.11.040
Korkhov VM, Milan-Lobo, L, Zuber B, Farhan H, Schmid, JA, Freissmuth M, Sitte HH.
Peptide-based interactions with calnexin target misassembled membrane proteins into endoplasmic reticulum-derived multilamellar bodies.
J Mol Biol. 2008 Apr 25;378(2):337-52. doi: 10.1016/j.jmb.2008.02.056
Meißlitzer-Ruppitsch C, Vetterlein M, Stangl H, Maier S, Neumüller J, Freissmuth M, Pavelka M, Ellinger A.
Electron microscopic visualization of fluorescent signals in cellular compartments and organelles by means of DAB-photoconversion.
Histochem Cell Biol. 2008 Aug;130(2):407-19. doi: 10.1007/s00418-008-0429-4
Reiterer V, Maier S, Sitte HH, Kriz A, Rüegg MA, Hauri HP, Freissmuth M, Farhan H.
Sec24- and ARFGAP1-dependent trafficking of GABA transporter-1 is a prerequisite for correct axonal targeting.
J Neurosci. 2008 Nov 19;28(47):12453-64. doi: 10.1523/JNEUROSCI.3451-08.2008
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