{ "types" : { "Bookmark" : { "pluralLabel" : "Bookmarks" }, "Publication" : { "pluralLabel" : "Publications" }, "GoldStandardPublication" : { "pluralLabel" : "GoldStandardPublications" }, "GoldStandardBookmark" : { "pluralLabel" : "GoldStandardBookmarks" }, "Tag" : { "pluralLabel" : "Tags" }, "User" : { "pluralLabel" : "Users" }, "Group" : { "pluralLabel" : "Groups" }, "Sphere" : { "pluralLabel" : "Spheres" } }, "properties" : { "count" : { "valueType" : "number" }, "date" : { "valueType" : "date" }, "changeDate" : { "valueType" : "date" }, "url" : { "valueType" : "url" }, "id" : { "valueType" : "url" }, "tags" : { "valueType" : "item" }, "user" : { "valueType" : "item" } }, "items" : [ { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2bae7aef327212f16fc0b0d659ffbcec7/pumaizi", "tags" : [ "2016","izi","morrison" ], "intraHash" : "bae7aef327212f16fc0b0d659ffbcec7", "interHash" : "da95808414f82d619138fcd51a287578", "label" : "FRET-Based Measurement of Apoptotic Caspase Activities by High-Throughput Screening Flow Cytometry", "user" : "pumaizi", "description" : "", "date" : "2026-04-01 10:46:46", "changeDate" : "2026-04-01 10:46:46", "count" : 1, "pub-type": "inbook", "booktitle": "Apoptosis Methods in Toxicology","publisher":"Springer New York","address":"New York, NY", "year": "2016", "url": "https://doi.org/10.1007/978-1-4939-3588-8_7", "author": [ "Christian T. Hellwig","Agnieszka H. Ludwig-Galezowska","Markus Rehm" ], "authors": [ {"first" : "Christian T.", "last" : "Hellwig"}, {"first" : "Agnieszka H.", "last" : "Ludwig-Galezowska"}, {"first" : "Markus", "last" : "Rehm"} ], "editor": [ "Perpetua M. Muganda" ], "editors": [ {"first" : "Perpetua M.", "last" : "Muganda"} ], "pages": "109--130","abstract": "Unwanted and excessive apoptosis contributes to various degenerative diseases, and apoptosis-inducing drugs are a mainstay of anticancer treatment regimens. The fields of pharmacology and toxicology consequently have a long history of investigating apoptotic cell death in the context of drug safety and efficacy studies. Canonical apoptotic cell death is crucially dependent on type II cysteinyl aspartate-specific proteases (caspases), and their activation is therefore widely used as a marker for this cell death modality. Here we describe a flow cytometric method for noninvasive, highly sensitive and reproducible FRET-based measurements of caspase activation. Compared to other flow cytometric techniques for apoptosis detection, this approach requires only minimal sample handling steps and provides a highly cost efficient option for large scale drug interaction studies and screens of compound libraries.", "isbn" : "978-1-4939-3588-8", "doi" : "10.1007/978-1-4939-3588-8_7", "bibtexKey": "Hellwig2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2f2513daff2164b815cfa4126e0473b11/pumaizi", "tags" : [ "2016","izi","pfizenmaier","kontermann" ], "intraHash" : "f2513daff2164b815cfa4126e0473b11", "interHash" : "9fe3241c0493c72d66015bee8c52efbd", "label" : "Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Proceedings of the National Academy of Sciences","publisher":"National Academy of Sciences", "year": "2016", "url": "http://www.pnas.org/lookup/doi/10.1073/pnas.1605195113", "author": [ "Yun Dong","Roman Fischer","Petrus J. W. Naudé","Olaf Maier","Csaba Nyakas","Maëlle Duffey","Eddy A. Van der Zee","Doortje Dekens","Wanda Douwenga","Andreas Herrmann","Eric Guenzi","Roland E. Kontermann","Klaus Pfizenmaier","Ulrich L. M. Eisel" ], "authors": [ {"first" : "Yun", "last" : "Dong"}, {"first" : "Roman", "last" : "Fischer"}, {"first" : "Petrus J. W.", "last" : "Naudé"}, {"first" : "Olaf", "last" : "Maier"}, {"first" : "Csaba", "last" : "Nyakas"}, {"first" : "Maëlle", "last" : "Duffey"}, {"first" : "Eddy A.", "last" : "Van der Zee"}, {"first" : "Doortje", "last" : "Dekens"}, {"first" : "Wanda", "last" : "Douwenga"}, {"first" : "Andreas", "last" : "Herrmann"}, {"first" : "Eric", "last" : "Guenzi"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Ulrich L. M.", "last" : "Eisel"} ], "volume": "113","number": "43","pages": "12304--12309","abstract": "huTNFR2 mice in supplement/methods", "isbn" : "1091-6490 (Electronic)$\\backslash$r0027-8424 (Linking)", "pmid" : "27791020", "issn" : "0027-8424", "doi" : "10.1073/pnas.1605195113", "bibtexKey": "Dong2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/283845f5fc2deb95a410a819781d32cf2/pumaizi", "tags" : [ "olayioye","2016","izi" ], "intraHash" : "83845f5fc2deb95a410a819781d32cf2", "interHash" : "d3f6fd4fedcb0c5489c2cde41332f8bb", "label" : "Spatial Rho regulation: Molecular mechanisms controlling the GAP protein DLC3", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Small GTPases","publisher":"Taylor & Francis", "year": "2016", "url": "https://www.tandfonline.com/doi/full/10.1080/21541248.2016.1260673", "author": [ "Janina Hendrick","Monilola A. Olayioye" ], "authors": [ {"first" : "Janina", "last" : "Hendrick"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "pages": "1--7","abstract": "ABSTRACTThe spatial regulation of cellular Rho signaling by GEF and GAP proteins and the molecular mechanisms controlling the Rho regulators themselves are still incompletely understood. We previously reported that the poorly characterized RhoGAP protein DLC3 localizes to cell-cell adhesions and Rab8-positive membrane tubules. However, it was unclear how DLC3 is targeted to these subcellular sites to execute its functions. In our recent work, protein partners of DLC3 were identified by mass spectrometry, identifying the basolateral polarity protein Scribble as a scaffold for DLC3 at cell-cell contacts. We found that the PDZ-mediated interaction of DLC3 and Scribble is essential for junctional DLC3 recruitment and its role as a local regulator of RhoA-ROCK signaling controlling adherens junction integrity and Scribble localization. Furthermore, DLC3 and Scribble depletion interfered with polarized lumen formation in a 3D model of cyst morphogenesis, emphasizing the relevance of both proteins in epithelial ...", "issn" : "21541256", "doi" : "10.1080/21541248.2016.1260673", "bibtexKey": "Hendrick2016a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/290b0319e32a9e0ba019cc416dd1ce10f/pumaizi", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "90b0319e32a9e0ba019cc416dd1ce10f", "interHash" : "dfbb566cca0bc7a52c0fed97637ad90c", "label" : "Advancing targeted co-stimulation with antibody-fusion proteins by introducing TNF superfamily members in a single-chain format", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "OncoImmunology","publisher":"Taylor & Francis", "year": "2016", "url": "https://www.tandfonline.com/doi/full/10.1080/2162402X.2016.1238540", "author": [ "Sina Fellermeier","Nadine Beha","Jan Erik Meyer","Sarah Ring","Stefan Bader","Roland E. Kontermann","Dafne Müller" ], "authors": [ {"first" : "Sina", "last" : "Fellermeier"}, {"first" : "Nadine", "last" : "Beha"}, {"first" : "Jan Erik", "last" : "Meyer"}, {"first" : "Sarah", "last" : "Ring"}, {"first" : "Stefan", "last" : "Bader"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Dafne", "last" : "Müller"} ], "volume": "5","number": "11","pages": "e1238540","abstract": "© 2016 Taylor & Francis Group, LLCCo-stimulation via receptors of the tumor necrosis factor superfamily (TNFSF) emerges as promising strategy to support antitumor immune responses. Targeted strategies with antibody-fusion proteins composed of a tumor-directed antibody part and the extracellular domain of a co-stimulatory ligand of the TNFSF constitute an attractive option to focus the co-stimulatory activity to the tumor site. Since TNFSF members intrinsically form functional units of non-covalently linked homotrimers, the protein engineering of suitable antibody-fusion proteins is challenging. Aiming for molecules of simple and stable configuration, we used TNFSF ligands in a single-chain format (scTNFSF), i.e., three units of the ectodomain connected by polypeptide linkers, folding into an intramolecular trimer. By fusing tumor-directed scFv antibody fragments directed against EpCAM or FAP to co-stimulatory scTNFSF molecules (sc4-1BBL, scOX40L, scGITRL or scLIGHT), a set of monomeric scFv-scTNFSF fusion proteins was generated. In comparison to the scFv-TNFSF format, defined by intermolecular homotrimerization via the TNFSF part, scFv-scTNFSF showed equal or enhanced co-stimulatory activity despite reduced avidity in antibody binding. In addition, enhanced serum stability and improved bioavailability in mice were observed. We show that the scFv-scTNFSF format can be applied to various members of the TNFSF, presenting targeting-dependent co-stimulatory activity. Hence, this format exhibits favorable properties that make it a promising choice for further therapeutic fusion protein development.", "pmid" : "27999756", "issn" : "2162402X", "doi" : "10.1080/2162402X.2016.1238540", "bibtexKey": "Fellermeier2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2c7c5e4d7d8f4dacf0df6dc24d7b0a37c/pumaizi", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "c7c5e4d7d8f4dacf0df6dc24d7b0a37c", "interHash" : "f772d5ca910c32c1a772dfcb6a3b3643", "label" : "Half-life extended biotherapeutics", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 4, "pub-type": "article", "journal": "Expert Opinion on Biological Therapy", "year": "2016", "url": "http://www.tandfonline.com/doi/full/10.1517/14712598.2016.1165661", "author": [ "Roland E. Kontermann" ], "authors": [ {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "16","number": "7","pages": "903--915","abstract": "INTRODUCTION: Many of the biotherapeutics approved or under development suffer from a short half-life necessitating frequent applications in order to maintain a therapeutic concentration over an extended period of time. The implementation of half-life extension strategies allows the generation of long-lasting therapeutics with improved pharmacokinetic and pharmacodynamic properties. Areas covered: This review gives an overview of the different half-life extension strategies developed over the past years and their application to generate next-generation biotherapeutics. It focuses on srategies already used in approved drugs and drugs that are in clinical development. These strategies include those aimed at increasing the hydrodynamic radius of the biotherapeutic and strategies which further implement recycling by the neonatal Fc receptor (FcRn). Expert opinion: Half-life extension strategies have become an integral part of development for many biotherapeutics. A diverse set of these strategies is available for the fine-tuning of half-life and adaption to the intended treatment modality and disease. Currently, half-life extension is dominated by strategies utilizing albumin binding or fusion, fusion to an immunoglobulin Fc$\\gamma$ region and PEGylation. However, a variety of alternative strategies, such as fusion of flexible polypeptide chains as PEG mimetic substitute, have reached advanced stages and offer further alternatives for half-life extension.", "pmid" : "26967759", "issn" : "1471-2598", "doi" : "10.1517/14712598.2016.1165661", "bibtexKey": "Kontermann2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/26e8e9d0d60fc2f7b3abb6d72a8fbc808/pumaizi", "tags" : [ "2016","izi","pfizenmaier","kontermann" ], "intraHash" : "6e8e9d0d60fc2f7b3abb6d72a8fbc808", "interHash" : "f056a5d46efc82c9bab50d147a6d12ea", "label" : "An optimized antibody-single-chain TRAIL fusion protein for cancer therapy", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "mAbs", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27064440", "author": [ "Martin Siegemund","Oliver Seifert","Maria Zarani","Tamara Dzinić","Valentino De Leo","Doris Göttsch","Sabine Münkel","Meike Hutt","Klaus Pfizenmaier","Roland E. Kontermann" ], "authors": [ {"first" : "Martin", "last" : "Siegemund"}, {"first" : "Oliver", "last" : "Seifert"}, {"first" : "Maria", "last" : "Zarani"}, {"first" : "Tamara", "last" : "Dzinić"}, {"first" : "Valentino", "last" : "De Leo"}, {"first" : "Doris", "last" : "Göttsch"}, {"first" : "Sabine", "last" : "Münkel"}, {"first" : "Meike", "last" : "Hutt"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "8","number": "5","pages": "879--891","abstract": "Fusion proteins combining oligomeric assemblies of a genetically obtained single-chain (sc) variant of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with antibodies directed against tumor-associated antigens represent a promising strategy to overcome the limited therapeutic activity of conventional soluble TRAIL. To further improve the scTRAIL module in order to obtain a robust, thermostable molecule of high activity, we performed a comprehensive analysis of the minimal TNF homology domain (THD) and optimized linkers between the three TRAIL subunits constituting a scTRAIL. Through a stepwise mutagenesis of the N- and C-terminal region and the joining linker sequences, we generated bioactive scTRAIL molecules comprising a covalent linkage of the C-terminal Val280 and the N-terminal position 122 by only two amino acid residues in combination with conservative exchanges at positions 122 and 279. The increased thermal stability and solubility of such optimized scTRAIL molecules translated into increased bioactivity in the diabody-scTRAIL (Db-scTRAIL) format, exemplified here for an epidermal growth factor receptor-specific Db-scTRAIL. Additional modifications within the diabody linkers resulted in a fusion protein exerting high, target-dependent apoptosis induction in tumor cell lines in vitro and potent antitumor activity in vivo. Our results illustrate that protein engineering of scTRAIL and associated peptide linkers provides a promising strategy to develop antibody-scTRAIL fusion proteins as effective antitumor therapeutics.", "isbn" : "19420862 (ISSN)", "pmid" : "27064440", "issn" : "19420870", "doi" : "10.1080/19420862.2016.1172163", "bibtexKey": "Siegemund2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2dc9fefa46171f6a7b04f991818195b71/pumaizi", "tags" : [ "olayioye","2016","izi","kontermann" ], "intraHash" : "dc9fefa46171f6a7b04f991818195b71", "interHash" : "32db979427f22ab19dfeac3d2a551809", "label" : "Oncogenic Ras triggers hyperproliferation and impairs polarized colonic morphogenesis by autocrine ErbB3 signaling.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Oncotarget", "year": "2016", "url": "https://doi.org/10.18632/oncotarget.10658", "author": [ "Yvonne Möller","Markus Morkel","Jens Schmid","Sven Beyes","Janina Hendrick","Michaela Strotbek","Pamela Riemer","Simone Schmid","Lisa C Schmitt","Roland Kontermann","Thomas Mürdter","Matthias Schwab","Christine Sers","Monilola a Olayioye" ], "authors": [ {"first" : "Yvonne", "last" : "Möller"}, {"first" : "Markus", "last" : "Morkel"}, {"first" : "Jens", "last" : "Schmid"}, {"first" : "Sven", "last" : "Beyes"}, {"first" : "Janina", "last" : "Hendrick"}, {"first" : "Michaela", "last" : "Strotbek"}, {"first" : "Pamela", "last" : "Riemer"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Lisa C", "last" : "Schmitt"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Thomas", "last" : "Mürdter"}, {"first" : "Matthias", "last" : "Schwab"}, {"first" : "Christine", "last" : "Sers"}, {"first" : "Monilola a", "last" : "Olayioye"} ], "volume": "7","number": "33","pages": "53526--53539","abstract": "Here we study the effects of inducible oncogenic K-Ras (G12V) expression on the polarized morphogenesis of colonic epithelial cells. We provide evidence that the autocrine production of heregulins, ligands for the ErbB3 receptor tyrosine kinase, is responsible for the hyperproliferation and aberrant 3D morphogenesis upon oncogenic K-Ras expression. This is in line with results obtained in primary intestinal organoid cultures, in which exogenous heregulin is shown to interfere with normal tissue architecture. Importantly, ErbB3 inhibition and heregulin gene silencing rescued K-RasG12V-induced features of cell transformation. Together with the increased ErbB3 positivity detected in human high-grade primary colorectal cancers, our findings provide support for an autocrine signaling loop engaged by oncogenic K-Ras involving ErbB3 that contributes to the dedifferentiation of the intestinal epithelium during tumor initiation and progression.", "pmid" : "27447549", "issn" : "19492553", "doi" : "10.18632/oncotarget.10658", "bibtexKey": "Moller2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e07db93d2ada433ceee859333e9eba07/pumaizi", "tags" : [ "olayioye","2016","izi" ], "intraHash" : "e07db93d2ada433ceee859333e9eba07", "interHash" : "25f0dd78fc11f653a76167af453717b1", "label" : "The polarity protein Scribble positions DLC3 at adherens junctions to regulate Rho signaling", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Cell Science", "year": "2016", "url": "http://jcs.biologists.org/lookup/doi/10.1242/jcs.190074", "author": [ "Janina Hendrick","Mirita Franz-Wachtel","Yvonne Moeller","Simone Schmid","Boris Macek","Monilola A. Olayioye" ], "authors": [ {"first" : "Janina", "last" : "Hendrick"}, {"first" : "Mirita", "last" : "Franz-Wachtel"}, {"first" : "Yvonne", "last" : "Moeller"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Boris", "last" : "Macek"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "129","number": "19","pages": "3583--3596","abstract": "The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By mass spectrometry we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 at cell-cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZL motif in DLC3. Both Scribble depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions and is required for their functional integrity. In a 3D model of cyst development, we furthermore show that DLC3 depletion impairs polarized morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus propose a novel function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells.", "isbn" : "0000000310932", "pmid" : "27505894", "issn" : "0021-9533", "doi" : "10.1242/jcs.190074", "bibtexKey": "Hendrick2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e53aaf6430f32ed2b065308cc0750330/pumaizi", "tags" : [ "2016","izi","morrison" ], "intraHash" : "e53aaf6430f32ed2b065308cc0750330", "interHash" : "bce326be35cafbe22dbb155b419602b4", "label" : "Predicting the cell death responsiveness and sensitization of glioma cells to TRAIL and temozolomide.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 4, "pub-type": "article", "journal": "Oncotarget","publisher":"Impact Journals", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27494880", "author": [ "Birgit C. Weyhenmeyer","Janis Noonan","Maximilian L. Würstle","Frank A. Lincoln","Grainne Johnston","Markus Rehm","Brona M. Murphy" ], "authors": [ {"first" : "Birgit C.", "last" : "Weyhenmeyer"}, {"first" : "Janis", "last" : "Noonan"}, {"first" : "Maximilian L.", "last" : "Würstle"}, {"first" : "Frank A.", "last" : "Lincoln"}, {"first" : "Grainne", "last" : "Johnston"}, {"first" : "Markus", "last" : "Rehm"}, {"first" : "Brona M.", "last" : "Murphy"} ], "volume": "7","number": "38","pages": "61295--61311","abstract": "Genotoxic chemotherapy with temozolomide (TMZ) is a mainstay of treatment for glioblastoma (GBM); however, at best, TMZ provides only modest survival benefit to a subset of patients. Recent insight into the heterogeneous nature of GBM suggests a more personalized approach to treatment may be necessary to overcome cancer drug resistance and improve patient care. These include novel therapies that can be used both alone and with TMZ to selectively reactivate apoptosis within malignant cells. For this approach to work, reliable molecular signatures that can accurately predict treatment responsiveness need to be identified first. Here, we describe the first proof-of-principle study that merges quantitative protein-based analysis of apoptosis signaling networks with data- and knowledge-driven mathematical systems modeling to predict treatment responsiveness of GBM cell lines to various apoptosis-inducing stimuli. These include monotherapies with TMZ and TRAIL, which activate the intrinsic and extrinsic apoptosis pathways, respectively, as well as combination therapies of TMZ+TRAIL. We also successfully employed this approach to predict whether individual GBM cell lines could be sensitized to TMZ or TRAIL via the selective targeting of Bcl-2/Bcl-xL proteins with ABT-737. Our findings suggest that systems biology-based approaches could assist in personalizing treatment decisions in GBM to optimize cell death induction.", "pmid" : "27494880", "issn" : "1949-2553", "doi" : "10.18632/oncotarget.10973", "bibtexKey": "Weyhenmeyer2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2eec3e9687bcd8ef549eb0bf368b90d53/pumaizi", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "eec3e9687bcd8ef549eb0bf368b90d53", "interHash" : "5a50969ed2a48b6910c786232b1f77d9", "label" : "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Biomaterials", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/26945457", "author": [ "Felista L. Tansi","Ronny Rüger","Claudia Böhm","Roland E. Kontermann","Ulf K. Teichgraeber","Alfred Fahr","Ingrid Hilger" ], "authors": [ {"first" : "Felista L.", "last" : "Tansi"}, {"first" : "Ronny", "last" : "Rüger"}, {"first" : "Claudia", "last" : "Böhm"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Ulf K.", "last" : "Teichgraeber"}, {"first" : "Alfred", "last" : "Fahr"}, {"first" : "Ingrid", "last" : "Hilger"} ], "volume": "88","pages": "70--82","abstract": "Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery.In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.", "isbn" : "4936419324993", "pmid" : "26945457", "issn" : "18785905", "doi" : "10.1016/j.biomaterials.2016.02.028", "bibtexKey": "Tansi2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/21da96a0410f3c67bba6353e604a18356/pumaizi", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "1da96a0410f3c67bba6353e604a18356", "interHash" : "70fdf76fa0d5ca7fd29b253248343567", "label" : "Pharmacokinetic properties of IgG and various Fc fusion proteins in mice", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 4, "pub-type": "article", "journal": "mAbs", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/26514880", "author": [ "Felix Unverdorben","Fabian Richter","Meike Hutt","Oliver Seifert","Pauline Malinge","Nicolas Fischer","Roland E. Kontermann" ], "authors": [ {"first" : "Felix", "last" : "Unverdorben"}, {"first" : "Fabian", "last" : "Richter"}, {"first" : "Meike", "last" : "Hutt"}, {"first" : "Oliver", "last" : "Seifert"}, {"first" : "Pauline", "last" : "Malinge"}, {"first" : "Nicolas", "last" : "Fischer"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "8","number": "1","pages": "120--128","abstract": "Fusion to an IgG Fc region is an established strategy to extend the half-life of therapeutic proteins. Most Fc fusion proteins, however, do not achieve the long half-life of IgGs. Based on findings that scFv-Fc fusion proteins exhibit a shorter half-life than the corresponding IgG molecules, we performed a comparative study of different antibody-derived Fc fusion proteins. We could confirm that fusion of single-chain Fv (scFv) and single-chain diabody (scDb) molecules to an Fc region yields in fusion proteins with substantially extended half-lives compared with the single-chain versions. However, even fusion proteins with a size similar to that of IgG, e.g., scDb-Fc, did not have a half-life as long as an IgG molecule. Binding to the neonatal Fc receptor (FcRn) under acidic and neutral conditions was similar for IgG and all Fc fusion proteins. However, we observed differences between IgG and the Fc fusion proteins for dissociation of FcRn-bound proteins induced by shifting from acidic to neutral pH, reflecting the physiological release mechanism, further supporting a contribution of the kinetics of pH-dependent release from FcRn to the pharmacokinetic properties of IgG and Fc fusion proteins.", "isbn" : "1942-0870 (Electronic)$\\backslash$r1942-0862 (Linking)", "pmid" : "26514880", "issn" : "19420870", "doi" : "10.1080/19420862.2015.1113360", "bibtexKey": "Unverdorben2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2018ee1a5b580532df9212cba805a67b5/pumaizi", "tags" : [ "2016","izi","hausser" ], "intraHash" : "018ee1a5b580532df9212cba805a67b5", "interHash" : "85ff8031f26f58308383fe6043da795a", "label" : "Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Molecular biology of the cell","publisher":"American Society for Cell Biology", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27852895", "author": [ "Zsófia Szíber","Hanna Liliom","Carlos O Oueslati Morales","Attila Ignácz","Anikó Erika Rátkai","Kornelia Ellwanger","Gisela Link","Attila Szűcs","Angelika Hausser","Katalin Schlett" ], "authors": [ {"first" : "Zsófia", "last" : "Szíber"}, {"first" : "Hanna", "last" : "Liliom"}, {"first" : "Carlos O Oueslati", "last" : "Morales"}, {"first" : "Attila", "last" : "Ignácz"}, {"first" : "Anikó Erika", "last" : "Rátkai"}, {"first" : "Kornelia", "last" : "Ellwanger"}, {"first" : "Gisela", "last" : "Link"}, {"first" : "Attila", "last" : "Szűcs"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Katalin", "last" : "Schlett"} ], "volume": "28","number": "2","pages": "mbc.E16--07--0526","abstract": "Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1 knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl non-receptor tyrosine kinases that participate in actin cytoskeleton remodelling.Here, we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons. Our results show that RIN1 affects the morphology of dendritic protrusions and accelerates dendritic filopodial motility through an Abl kinase dependent pathway. Lack of RIN1 results in enhanced mEPSC amplitudes indicating an increase in surface AMPA receptor levels compared to wild type neurons. We further provide evidence that the Rab5 GEF activity of RIN1 regulates surface GluA1 subunit endocytosis. Consequently, loss of RIN1 blocks surface AMPA receptor downregulation evoked by chemically induced long-term depression.Our findings indicate that RIN1 destabilizes synaptic connections and is a key player in postsynaptic AMPA receptor endocytosis, providing multiple ways of negatively regulating memory stabilisation during neuronal plasticity.", "pmid" : "27852895", "issn" : "1939-4586", "doi" : "10.1091/mbc.E16-07-0526", "bibtexKey": "Sziber2017" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2286199973920f9dfec7bc1cd2d605655/pumaizi", "tags" : [ "2016","izi","pfizenmaier" ], "intraHash" : "286199973920f9dfec7bc1cd2d605655", "interHash" : "eac7d7da3d700814c3b9c2de7e4f66e2", "label" : "Selective blocking of TNF receptor 1 attenuates peritoneal dialysis fluid induced inflammation of the peritoneum in mice", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "PLoS ONE", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27755542", "author": [ "Florian Kälble","Janine Damaske","Danijela Heide","Iris Arnold","Fabian Richter","Olaf Maier","Ulrich Eisel","Peter Scheurich","Klaus Pfizenmaier","Martin Zeier","Vedat Schwenger","Julia Ranzinger" ], "authors": [ {"first" : "Florian", "last" : "Kälble"}, {"first" : "Janine", "last" : "Damaske"}, {"first" : "Danijela", "last" : "Heide"}, {"first" : "Iris", "last" : "Arnold"}, {"first" : "Fabian", "last" : "Richter"}, {"first" : "Olaf", "last" : "Maier"}, {"first" : "Ulrich", "last" : "Eisel"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Martin", "last" : "Zeier"}, {"first" : "Vedat", "last" : "Schwenger"}, {"first" : "Julia", "last" : "Ranzinger"} ], "editor": [ "Gautam Sethi" ], "editors": [ {"first" : "Gautam", "last" : "Sethi"} ], "volume": "11","number": "10","pages": "e0163314","abstract": "Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects.", "pmid" : "27755542", "issn" : "19326203", "doi" : "10.1371/journal.pone.0163314", "bibtexKey": "Kalble2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2397cf6d7c3ca520210b818d8a3a28b0e/pumaizi", "tags" : [ "2016","izi","hausser" ], "intraHash" : "397cf6d7c3ca520210b818d8a3a28b0e", "interHash" : "b18c243e82bf272cb219a2627452c7f0", "label" : "Tailored parameter optimization methods for ordinary differential equation models with steady-state constraints", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 5, "pub-type": "article", "journal": "BMC Systems Biology", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27549154", "author": [ "Anna Fiedler","Sebastian Raeth","Fabian J. Theis","Angelika Hausser","Jan Hasenauer" ], "authors": [ {"first" : "Anna", "last" : "Fiedler"}, {"first" : "Sebastian", "last" : "Raeth"}, {"first" : "Fabian J.", "last" : "Theis"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Jan", "last" : "Hasenauer"} ], "volume": "10","number": "1","pages": "80","abstract": "Ordinary differential equation (ODE) models are widely used to describe (bio-)chemical and biological processes. To enhance the predictive power of these models, their unknown parameters are estimated from experimental data. These experimental data are mostly collected in perturbation experiments, in which the processes are pushed out of steady state by applying a stimulus. The information that the initial condition is a steady state of the unperturbed process provides valuable information, as it restricts the dynamics of the process and thereby the parameters. However, implementing steady-state constraints in the optimization often results in convergence problems. In this manuscript, we propose two new methods for solving optimization problems with steady-state constraints. The first method exploits ideas from optimization algorithms on manifolds and introduces a retraction operator, essentially reducing the dimension of the optimization problem. The second method is based on the continuous analogue of the optimization problem. This continuous analogue is an ODE whose equilibrium points are the optima of the constrained optimization problem. This equivalence enables the use of adaptive numerical methods for solving optimization problems with steady-state constraints. Both methods are tailored to the problem structure and exploit the local geometry of the steady-state manifold and its stability properties. A parameterization of the steady-state manifold is not required. The efficiency and reliability of the proposed methods is evaluated using one toy example and two applications. The first application example uses published data while the second uses a novel dataset for Raf/MEK/ERK signaling. The proposed methods demonstrated better convergence properties than state-of-the-art methods employed in systems and computational biology. Furthermore, the average computation time per converged start is significantly lower. In addition to the theoretical results, the analysis of the dataset for Raf/MEK/ERK signaling provides novel biological insights regarding the existence of feedback regulation. Many optimization problems considered in systems and computational biology are subject to steady-state constraints. While most optimization methods have convergence problems if these steady-state constraints are highly nonlinear, the methods presented recover the convergence properties of optimizers which can exploit an analytical expression for the parameter-dependent steady state. This renders them an excellent alternative to methods which are currently employed in systems and computational biology.", "isbn" : "1291801603197", "pmid" : "27549154", "issn" : "17520509", "doi" : "10.1186/s12918-016-0319-7", "bibtexKey": "Fiedler2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2c7c5e4d7d8f4dacf0df6dc24d7b0a37c/fabian", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "c7c5e4d7d8f4dacf0df6dc24d7b0a37c", "interHash" : "f772d5ca910c32c1a772dfcb6a3b3643", "label" : "Half-life extended biotherapeutics", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 4, "pub-type": "article", "journal": "Expert Opinion on Biological Therapy", "year": "2016", "url": "http://www.tandfonline.com/doi/full/10.1517/14712598.2016.1165661", "author": [ "Roland E. Kontermann" ], "authors": [ {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "16","number": "7","pages": "903--915","abstract": "INTRODUCTION: Many of the biotherapeutics approved or under development suffer from a short half-life necessitating frequent applications in order to maintain a therapeutic concentration over an extended period of time. The implementation of half-life extension strategies allows the generation of long-lasting therapeutics with improved pharmacokinetic and pharmacodynamic properties. Areas covered: This review gives an overview of the different half-life extension strategies developed over the past years and their application to generate next-generation biotherapeutics. It focuses on srategies already used in approved drugs and drugs that are in clinical development. These strategies include those aimed at increasing the hydrodynamic radius of the biotherapeutic and strategies which further implement recycling by the neonatal Fc receptor (FcRn). Expert opinion: Half-life extension strategies have become an integral part of development for many biotherapeutics. A diverse set of these strategies is available for the fine-tuning of half-life and adaption to the intended treatment modality and disease. Currently, half-life extension is dominated by strategies utilizing albumin binding or fusion, fusion to an immunoglobulin Fc$\\gamma$ region and PEGylation. However, a variety of alternative strategies, such as fusion of flexible polypeptide chains as PEG mimetic substitute, have reached advanced stages and offer further alternatives for half-life extension.", "pmid" : "26967759", "issn" : "1471-2598", "doi" : "10.1517/14712598.2016.1165661", "bibtexKey": "Kontermann2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/26e8e9d0d60fc2f7b3abb6d72a8fbc808/fabian", "tags" : [ "2016","izi","pfizenmaier","kontermann" ], "intraHash" : "6e8e9d0d60fc2f7b3abb6d72a8fbc808", "interHash" : "f056a5d46efc82c9bab50d147a6d12ea", "label" : "An optimized antibody-single-chain TRAIL fusion protein for cancer therapy", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "mAbs", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/27064440", "author": [ "Martin Siegemund","Oliver Seifert","Maria Zarani","Tamara Dzinić","Valentino De Leo","Doris Göttsch","Sabine Münkel","Meike Hutt","Klaus Pfizenmaier","Roland E. Kontermann" ], "authors": [ {"first" : "Martin", "last" : "Siegemund"}, {"first" : "Oliver", "last" : "Seifert"}, {"first" : "Maria", "last" : "Zarani"}, {"first" : "Tamara", "last" : "Dzinić"}, {"first" : "Valentino", "last" : "De Leo"}, {"first" : "Doris", "last" : "Göttsch"}, {"first" : "Sabine", "last" : "Münkel"}, {"first" : "Meike", "last" : "Hutt"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "8","number": "5","pages": "879--891","abstract": "Fusion proteins combining oligomeric assemblies of a genetically obtained single-chain (sc) variant of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with antibodies directed against tumor-associated antigens represent a promising strategy to overcome the limited therapeutic activity of conventional soluble TRAIL. To further improve the scTRAIL module in order to obtain a robust, thermostable molecule of high activity, we performed a comprehensive analysis of the minimal TNF homology domain (THD) and optimized linkers between the three TRAIL subunits constituting a scTRAIL. Through a stepwise mutagenesis of the N- and C-terminal region and the joining linker sequences, we generated bioactive scTRAIL molecules comprising a covalent linkage of the C-terminal Val280 and the N-terminal position 122 by only two amino acid residues in combination with conservative exchanges at positions 122 and 279. The increased thermal stability and solubility of such optimized scTRAIL molecules translated into increased bioactivity in the diabody-scTRAIL (Db-scTRAIL) format, exemplified here for an epidermal growth factor receptor-specific Db-scTRAIL. Additional modifications within the diabody linkers resulted in a fusion protein exerting high, target-dependent apoptosis induction in tumor cell lines in vitro and potent antitumor activity in vivo. Our results illustrate that protein engineering of scTRAIL and associated peptide linkers provides a promising strategy to develop antibody-scTRAIL fusion proteins as effective antitumor therapeutics.", "isbn" : "19420862 (ISSN)", "pmid" : "27064440", "issn" : "19420870", "doi" : "10.1080/19420862.2016.1172163", "bibtexKey": "Siegemund2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2dc9fefa46171f6a7b04f991818195b71/fabian", "tags" : [ "olayioye","2016","izi","kontermann" ], "intraHash" : "dc9fefa46171f6a7b04f991818195b71", "interHash" : "32db979427f22ab19dfeac3d2a551809", "label" : "Oncogenic Ras triggers hyperproliferation and impairs polarized colonic morphogenesis by autocrine ErbB3 signaling.", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Oncotarget", "year": "2016", "url": "https://doi.org/10.18632/oncotarget.10658", "author": [ "Yvonne Möller","Markus Morkel","Jens Schmid","Sven Beyes","Janina Hendrick","Michaela Strotbek","Pamela Riemer","Simone Schmid","Lisa C Schmitt","Roland Kontermann","Thomas Mürdter","Matthias Schwab","Christine Sers","Monilola a Olayioye" ], "authors": [ {"first" : "Yvonne", "last" : "Möller"}, {"first" : "Markus", "last" : "Morkel"}, {"first" : "Jens", "last" : "Schmid"}, {"first" : "Sven", "last" : "Beyes"}, {"first" : "Janina", "last" : "Hendrick"}, {"first" : "Michaela", "last" : "Strotbek"}, {"first" : "Pamela", "last" : "Riemer"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Lisa C", "last" : "Schmitt"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Thomas", "last" : "Mürdter"}, {"first" : "Matthias", "last" : "Schwab"}, {"first" : "Christine", "last" : "Sers"}, {"first" : "Monilola a", "last" : "Olayioye"} ], "volume": "7","number": "33","pages": "53526--53539","abstract": "Here we study the effects of inducible oncogenic K-Ras (G12V) expression on the polarized morphogenesis of colonic epithelial cells. We provide evidence that the autocrine production of heregulins, ligands for the ErbB3 receptor tyrosine kinase, is responsible for the hyperproliferation and aberrant 3D morphogenesis upon oncogenic K-Ras expression. This is in line with results obtained in primary intestinal organoid cultures, in which exogenous heregulin is shown to interfere with normal tissue architecture. Importantly, ErbB3 inhibition and heregulin gene silencing rescued K-RasG12V-induced features of cell transformation. Together with the increased ErbB3 positivity detected in human high-grade primary colorectal cancers, our findings provide support for an autocrine signaling loop engaged by oncogenic K-Ras involving ErbB3 that contributes to the dedifferentiation of the intestinal epithelium during tumor initiation and progression.", "pmid" : "27447549", "issn" : "19492553", "doi" : "10.18632/oncotarget.10658", "bibtexKey": "Moller2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e07db93d2ada433ceee859333e9eba07/fabian", "tags" : [ "olayioye","2016","izi" ], "intraHash" : "e07db93d2ada433ceee859333e9eba07", "interHash" : "25f0dd78fc11f653a76167af453717b1", "label" : "The polarity protein Scribble positions DLC3 at adherens junctions to regulate Rho signaling", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Journal of Cell Science", "year": "2016", "url": "http://jcs.biologists.org/lookup/doi/10.1242/jcs.190074", "author": [ "Janina Hendrick","Mirita Franz-Wachtel","Yvonne Moeller","Simone Schmid","Boris Macek","Monilola A. Olayioye" ], "authors": [ {"first" : "Janina", "last" : "Hendrick"}, {"first" : "Mirita", "last" : "Franz-Wachtel"}, {"first" : "Yvonne", "last" : "Moeller"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Boris", "last" : "Macek"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "129","number": "19","pages": "3583--3596","abstract": "The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By mass spectrometry we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 at cell-cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZL motif in DLC3. Both Scribble depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions and is required for their functional integrity. In a 3D model of cyst development, we furthermore show that DLC3 depletion impairs polarized morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus propose a novel function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells.", "isbn" : "0000000310932", "pmid" : "27505894", "issn" : "0021-9533", "doi" : "10.1242/jcs.190074", "bibtexKey": "Hendrick2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2eec3e9687bcd8ef549eb0bf368b90d53/fabian", "tags" : [ "2016","izi","kontermann" ], "intraHash" : "eec3e9687bcd8ef549eb0bf368b90d53", "interHash" : "5a50969ed2a48b6910c786232b1f77d9", "label" : "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Biomaterials", "year": "2016", "url": "http://www.ncbi.nlm.nih.gov/pubmed/26945457", "author": [ "Felista L. Tansi","Ronny Rüger","Claudia Böhm","Roland E. Kontermann","Ulf K. Teichgraeber","Alfred Fahr","Ingrid Hilger" ], "authors": [ {"first" : "Felista L.", "last" : "Tansi"}, {"first" : "Ronny", "last" : "Rüger"}, {"first" : "Claudia", "last" : "Böhm"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Ulf K.", "last" : "Teichgraeber"}, {"first" : "Alfred", "last" : "Fahr"}, {"first" : "Ingrid", "last" : "Hilger"} ], "volume": "88","pages": "70--82","abstract": "Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery.In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.", "isbn" : "4936419324993", "pmid" : "26945457", "issn" : "18785905", "doi" : "10.1016/j.biomaterials.2016.02.028", "bibtexKey": "Tansi2016" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2f2513daff2164b815cfa4126e0473b11/fabian", "tags" : [ "2016","izi","pfizenmaier","kontermann" ], "intraHash" : "f2513daff2164b815cfa4126e0473b11", "interHash" : "9fe3241c0493c72d66015bee8c52efbd", "label" : "Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Proceedings of the National Academy of Sciences","publisher":"National Academy of Sciences", "year": "2016", "url": "http://www.pnas.org/lookup/doi/10.1073/pnas.1605195113", "author": [ "Yun Dong","Roman Fischer","Petrus J. W. Naudé","Olaf Maier","Csaba Nyakas","Maëlle Duffey","Eddy A. Van der Zee","Doortje Dekens","Wanda Douwenga","Andreas Herrmann","Eric Guenzi","Roland E. Kontermann","Klaus Pfizenmaier","Ulrich L. M. Eisel" ], "authors": [ {"first" : "Yun", "last" : "Dong"}, {"first" : "Roman", "last" : "Fischer"}, {"first" : "Petrus J. W.", "last" : "Naudé"}, {"first" : "Olaf", "last" : "Maier"}, {"first" : "Csaba", "last" : "Nyakas"}, {"first" : "Maëlle", "last" : "Duffey"}, {"first" : "Eddy A.", "last" : "Van der Zee"}, {"first" : "Doortje", "last" : "Dekens"}, {"first" : "Wanda", "last" : "Douwenga"}, {"first" : "Andreas", "last" : "Herrmann"}, {"first" : "Eric", "last" : "Guenzi"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Ulrich L. M.", "last" : "Eisel"} ], "volume": "113","number": "43","pages": "12304--12309","abstract": "huTNFR2 mice in supplement/methods", "isbn" : "1091-6490 (Electronic)$\\backslash$r0027-8424 (Linking)", "pmid" : "27791020", "issn" : "0027-8424", "doi" : "10.1073/pnas.1605195113", "bibtexKey": "Dong2016" } ] }