Research Topics
| Volker BrinkmannSummaryAffiliation: Novartis Institutes for BioMedical Research Publications
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Detail Information
Publications
Pulmonary and vascular pharmacology of sphingosine 1-phosphateVolker Brinkmann
Autoimmunity and Transplantation, Novartis Institutes for BioMedical Research, WSJ 386 101, Lichtstrasse 35, CH 4002 Basel, Switzerland
Curr Opin Pharmacol 6:244-50. 2006....- The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivoYuk Yuen Lan
Thomas E Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Am J Transplant 5:2649-59. 2005..Transendothelial migration of FTY720-P-treated immature DCs to the CCR7 ligand CCL19 was reduced. These novel data suggest that modulation of DC trafficking by FTY720 may contribute to its immunosuppressive effects... 
Transgenic, fluorescent Leishmania mexicana allow direct analysis of the proteome of intracellular amastigotesDaniel Paape
Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, United Kingdom
Mol Cell Proteomics 7:1688-701. 2008..Last but not least, at 6% coverage the proteome identified all vaccine antigens tested to date. Thus, the present data set provides a valuable resource for selection of candidate vaccine antigens...- FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous systemVolker Brinkmann
Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland
Br J Pharmacol 158:1173-82. 2009..Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed... - Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacologyVolker Brinkmann
Autoimmunity and Transplantation, Novartis Institutes for BioMedical Research, Lichtstrasse 35, CH 4002 Basel, Switzerland
Pharmacol Ther 115:84-105. 2007..This review provides an overview on S1P activities and S1P receptor function in health and disease, and summarizes the clinical experience with FTY720 in transplantation and multiple sclerosis... 
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosisVolker Brinkmann
Department of Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Novartis Campus Forum 1, WSJ 386, CH 4056 Basel, Switzerland
Nat Rev Drug Discov 9:883-97. 2010....- Modulation of T cell homeostasis and alloreactivity under continuous FTY720 exposureBarbara Metzler
Department of Autoimmunity and Transplantation, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
Int Immunol 20:633-44. 2008.... - FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier functionVolker Brinkmann
Transplantation and Immunology, Novartis Institutes for BioMedical Research, Basel, Switzerland
Am J Transplant 4:1019-25. 2004..The available data establish S1P(1) as a key target for FTY720, and further point to therapeutically relevant effects of the drug on lymphocytes and vascular endothelium... - FTY720, an immunomodulatory sphingolipid mimetic: translation of a novel mechanism into clinical benefit in multiple sclerosisThomas Baumruker
Novartis Institutes for BioMedical Research, Autoimmunity and Transplantation, Brunner Strasse 59, A 1235 Vienna, Austria
Expert Opin Investig Drugs 16:283-9. 2007.... - FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunityVolker Brinkmann
Novartis Pharma AG Transplantation Research WSJ 386 101, CH 4002 Basel, Switzerland
Curr Opin Immunol 14:569-75. 2002..Stimulation of sphingosine 1-phosphate receptors leads to sequestration of lymphocytes in secondary lymphatic tissues and thus away from inflammatory lesions and graft sites... - FTY720: mechanism of action and potential benefit in organ transplantationVolker Brinkmann
Novartis Institutes for BioMedical Research, Auto Immunity and Transplantation, WSJ 386 101, CH 4002 Basel, Switzerland
Yonsei Med J 45:991-7. 2004..This review summarises the mechanism of action of FTY720, its effects in models of transplantation and autoimmunity, and results from clinical trials in humans... - FTY720 preferentially depletes naive T cells from peripheral and lymphoid organsMatthias Hofmann
Novartis Institutes for BioMedical Research, Transplantation Research, Autoimmunity Transplantation Disease Area, Novartis Pharma AG, Basel, Switzerland
Int Immunopharmacol 6:1902-10. 2006..This suggests that treatment with FTY720 may not interfere with immune functions mediated locally by tissue-resident peripheral effector/memory T cells... - Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomerRainer Albert
Novartis Institutes for BioMedical Research, Lichtstrasse 35, WSJ 507 3 02, CH 4056 Basel, Switzerland
J Med Chem 48:5373-7. 2005..Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction... - Impact of sphingosine 1-phosphate modulation on immune outcomesDaniel D Pinschewer
Department of Pathology and Immunology, University of Geneva, Geneva
Neurology 76:S15-9. 2011..However, in patients, long-term observation is important as both the risk of cancer and infection is potentially increased by the use of any immunomodulatory agent... - T-cell depletion and graft survival induced by anti-human CD3 immunotoxins in human CD3epsilon transgenic miceMarla Weetall
Novartis Pharmaceuticals, Summit, New Jersey 07901, USA
Transplantation 73:1658-66. 2002..However, the anti-CD3 immunotoxins used in animal studies do not cross-react with human T cells, limiting extrapolation to humans and hindering clinical development... - The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activationJean Pierre Evenou
Novartis Institute for Biomedical Research, WSJ 386 5 27, CH 4002 Basel, Switzerland
J Pharmacol Exp Ther 330:792-801. 2009..The mode of action of AEB071 is different from that of calcineurin inhibitors, and AEB071 and cyclosporine A seem to have complementary effects on T-cell signaling pathways... - Long-term islet graft survival in streptozotocin- and autoimmune-induced diabetes models by immunosuppressive and potential insulinotropic agent FTY720Fumin Fu
Novartis Institute for Biomedical Research, Summit, New Jersey; Novartis Pharma AG, Basel, Switzerland
Transplantation 73:1425-30. 2002..The effect is likely attributable to its action in preventing effector lymphocyte infiltration into the grafted tissue... - The immune modulator FTY720 targets sphingosine 1-phosphate receptorsVolker Brinkmann
Department of Transplantation, Novartis Pharma AG, Lichtstrasse 35, CH 4002 Basel, Switzerland
J Biol Chem 277:21453-7. 2002..Our results suggest that FTY720, after phosphorylation, acts through sphingosine 1-phosphate signaling pathways to modulate chemotactic responses and lymphocyte trafficking... - Efficacy and safety of ABI793, a novel human anti-human CD154 monoclonal antibody, in cynomolgus monkey renal allotransplantationWalter Schuler
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
Transplantation 77:717-26. 2004..This is the first report on the efficacy and safety of ABI793, a novel human anti-human CD154 mAb, in Cynomolgus renal transplant recipients... - A potent and selective S1P(1) antagonist with efficacy in experimental autoimmune encephalomyelitisJean Quancard
Novartis Institutes for BioMedical Research, CH 4056 Basel, Switzerland
Chem Biol 19:1142-51. 2012..In addition, the profile of NIBR-0213 makes it an attractive candidate to further study the consequences of S1P(1) receptor antagonism and to differentiate the effects from those of S1P(1) agonists... - Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesionsTimothy J Seabrook
Department of Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland
J Neuroinflammation 7:95. 2010..Therefore we examined angiogenic promoting factors in MS and EAE lesions to determine if there were changes in blood vessel density at different stages of EAE... - The sphingosine 1-phosphate receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cellsTakafumi Kimura
Department of Medicine II, University of Tubingen, Otfried Muller Strasse 10, 72076 Tubingen, Germany
Blood 103:4478-86. 2004..In the hematopoietic microenvironment, S1PRs are involved in migration and maintenance of HPCs by modulating the effects of SDF-1... - A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation modelShifeng Pan
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA
Chem Biol 13:1227-34. 2006..This demonstrates that a selective agonist of the S1P(1) receptor is sufficient to achieve efficacy in an animal model of transplantation... - Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptorDirk H Walter
Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Arterioscler Thromb Vasc Biol 27:275-82. 2007.... - FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient miceJerzy Roch Nofer
Institut fur Klinische Chemie und Laboratoriumsmedizin, Westfalische Wilhelms Universitat Munster, Albert Schweizer Str 33, D 48129 Munster, Germany
Circulation 115:501-8. 2007..The present study was undertaken to investigate whether modulation of S1P signaling would affect atherosclerosis in a murine model of disease... - Increased resistance of LFA-1-deficient mice to lipopolysaccharide-induced shock/liver injury in the presence of TNF-alpha and IL-12 is mediated by IL-10: a novel role for LFA-1 in the regulation of the proinflammatory and anti-inflammatory cytokine balanMasashi Emoto
Department of Immunology and Central Core Facility Microscopy, Max Planck Institute for Infection Biology, Berlin, Germany
J Immunol 171:584-93. 2003..Our data point to a novel role of LFA-1 in control of the proinflammatory/anti-inflammatory cytokine network... - The immune modulator FYT720 prevents autoimmune diabetes in nonobese diabetic mice small star, filledZandong Yang
Department of Internal Medicine, P O Box 801413, University of Virginia, Charlottesville, VA 22908, USA
Clin Immunol 107:30-5. 2003..These results suggest that FTY720 may be effective in prevention of autoimmune diabetes or in slowing its progression... - Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD)Patricia A Taylor
Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, 420 Delaware Street SE, Minneapolis, MN 55455, USA
Blood 110:3480-8. 2007..Our data further define the mechanisms of action and provide insight as to the potential clinical uses of FTY in allogeneic bone marrow transplant recipients... - Requirement of secondary lymphoid tissues for the induction of primary and secondary T cell responses against Listeria monocytogenesMischo Kursar
Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany
Eur J Immunol 38:127-38. 2008..Overall, these results indicate that not only primary T cell responses, but also secondary T cell responses, highly depend on the lymphoid environment for effective activation... - Neutrophilia in LFA-1-deficient mice confers resistance to listeriosis: possible contribution of granulocyte-colony-stimulating factor and IL-17Mamiko Miyamoto
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
J Immunol 170:5228-34. 2003..Consequently, we conclude that increased resistance of LFA-1(-/-) mice to listeriosis is due to neutrophilia facilitating liver infiltration by granulocytes promptly after L. monocytogenes infection, although it is LFA-1 independent... - Delay of phagosome maturation by a mycobacterial lipid is reversed by nitric oxideSofia Axelrod
Department of Immunology, Max Planck Institute for Infection Biology, D 10117 Berlin, Germany
Cell Microbiol 10:1530-45. 2008..Thus, specific host defence effectors of activated macrophages directly target a specific virulence function of mycobacteria... - FTY720 pretreatment reduces warm hepatic ischemia reperfusion injury through inhibition of T-lymphocyte infiltrationDean M Anselmo
Dumont-UCLA Transplant Center, UCLA School of Medicine, Los Angeles, CA 90095-7054, USA
Am J Transplant 2:843-9. 2002..Myeloperoxidase data suggest this mechanism is independent of neutrophil activation. These results indicate that T lymphocytes are pivotal mediators in hepatic IR and may have important implications in liver transplantation... - Oral efficacy of the new immunomodulator FTY720 in cynomolgus monkey kidney allotransplantation, given alone or in combination with cyclosporine or RADHenk Jan Schuurman
Transplantation Research, Novartis Pharma AG, Basel, Switzerland Presently, Immerge BioTherapeutics, Charlestown, MA 02129, USA
Transplantation 74:951-60. 2002..We investigated its efficacy, either FTY720 alone or together with cyclosporine or the rapamycin derivative rapamycin derivative (RAD), in cynomolgus monkey kidney allotransplantation... - Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological propertiesFlorenz Sasse
GBF, Gesellschaft fur Biotechnologische Forschung mbH, Abteilung Naturstoffbiologie, Mascheroder Weg 1, D 38124 Braunschweig, Germany
J Antibiot (Tokyo) 55:543-51. 2002..All argyrins had slight antibiotic activity, especially against Pseudomonas sp., and inhibited growth of mammalian cell cultures. The growth inhibition was often incomplete and varied highly with different cell lines... - The IFN-inducible Golgi- and endoplasmic reticulum- associated 47-kDa GTPase IIGP is transiently expressed during listeriosisJens Zerrahn
Department of Immunology and Core Facility Microscopy, Max Planck Institute for Infectionbiology, Berlin, Germany
J Immunol 168:3428-36. 2002..We conclude that IIGP exerts a distinct role in IFN-induced intracellular membrane trafficking or processing... - Neisserial immunoglobulin A1 protease induces specific T-cell responses in humansAnastasios Tsirpouchtsidis
Abteilung Molekulare Biologie. Zentralbereich Mikroskopie, , D-10117 Berlin, Germany
Infect Immun 70:335-44. 2002..These findings support the significance of IgA1 protease as a virulence determinant of bacterial meningitis and its function as a dominant proinflammatory T-cell antigen... - Anticancer activity of FTY720: phosphorylated FTY720 inhibits autotaxin, a metastasis-enhancing and angiogenic lysophospholipase DLaurens A van Meeteren
Division of Cellular Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, 1066 Amsterdam, The Netherlands
Cancer Lett 266:203-8. 2008..After oral administration in mice, FTY720 (3mg/kg) significantly reduced plasma LPA levels. These results suggest that FTY720 may exert its anticancer effects, at least in part, by targeting the ATX-LPA axis... - Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1Mehrdad Matloubian
Howard Hughes Medical Institute and Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0414, USA
Nature 427:355-60. 2004..These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs... - Saposin C is required for lipid presentation by human CD1bFlorian Winau
Max Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 21 22, D 10117 Berlin, Germany
Nat Immunol 5:169-74. 2004..We propose a model in which SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b. Thus, SAP-C represents a missing link in antigen presentation of lipids through CD1b to human T cells... - Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720Elzbieta Sawicka
Novartis Horsham Research Centre, Horsham, U.K
J Immunol 171:6206-14. 2003.... - The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel ILev Koyrakh
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
Am J Transplant 5:529-36. 2005..In contrast, the HR reduction induced by FTY720 in I(KACh)-deficient mice was blunted. We conclude that the effect of acute FTY720 administration on HR is mediated primarily by I(KACh) activation... - Immunomodulator FTY720 Induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3Markus Tölle
Med Klinik IV, Charite Campus Benjamin Franklin, Berlin, Germany
Circ Res 96:913-20. 2005.... - Protection of mouse small bowel allografts by FTY720 and costimulation blockadeSheng Yan
Department of Surgery, The 1st Affiliated Hospital of Zhejiang University, Zhejiang, China
Transplantation 79:1703-10. 2005..CONCLUSION: FTY720 plus MR1 effectively inhibited intestinal allograft rejection in mice, possibly by enhancing the alloprotective effects of costimulation blockade by prolonged sequestration of lymphocytes in secondary lymphoid organs... - Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migrationKrishnaraj Rajalingam
Department of Molecular Biology, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, D 10117 Berlin, Germany
Nat Cell Biol 7:837-43. 2005..Our data show an unexpected role of prohibitin in the activation of the Ras-Raf signalling pathway and in modulating epithelial cell adhesion and migration... - Highly biased type 1 immune responses in mice deficient in LFA-1 in Listeria monocytogenes infection are caused by elevated IL-12 production by granulocytesMasashi Emoto
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
J Immunol 171:3970-6. 2003..In conclusion, LFA-1 regulates type 1 immune responses by controlling prompt infiltration of IL-12-producing granulocytes into sites of inflammation... - FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistanceHiroshi Yasui
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Cancer Res 65:7478-84. 2005..These results suggest that FTY720 overcomes drug resistance in multiple myeloma cells and provide the rationale for its clinical evaluation to improve patient outcome in multiple myeloma... - Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeabilityTeresa Sanchez
Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3501, USA
J Biol Chem 278:47281-90. 2003.... - A novel low molecular weight inhibitor of dendritic cells and B cells blocks allergic inflammationPeter Ettmayer
Novartis Institutes for Biomedical Research Vienna, Brunnerstrasse 59, A-1230 Vienna, Austria
Am J Respir Crit Care Med 173:599-606. 2006..CONCLUSION: VAF347 represents a novel type of immunomodulator by affecting two major pathways in allergic airway pathogenesis: dendritic cell-mediated T-helper-cell activation and induction of IgE production by human B lymphocytes... - Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice treated with FTY720Margaret A Morris
Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
Eur J Immunol 35:3570-80. 2005..Our data indicate that the commonly held belief that FTY720 blocks lymphocyte egress from lymph nodes cannot fully explain the lymphocyte dynamics observed with prolonged treatment... - Novel insights into the mechanism of action of FTY720 in a transgenic model of allograft rejection: implications for therapy of chronic rejectionAntje Habicht
Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital, Boston, MA 02115, USA
J Immunol 176:36-42. 2006..These data have important implications for targeting the sphingosine 1-phosphate receptor 1 in solid organ transplantation... - The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4+/CD25+ T-regulatory cells and enhances their functional activityElzbieta Sawicka
Novartis Institutes for BioMedical Research, Horsham, West Sussex, United Kingdom
J Immunol 175:7973-80. 2005..Thus, FTY720 differentially affects the sequestration of T-regulatory cells and importantly, increases the functional activity of T-regulatory cells, suggesting that it may have disease-modifying potential in inflammatory disorders... - A small non-coding RNA of the invasion gene island (SPI-1) represses outer membrane protein synthesis from the Salmonella core genomeVerena Pfeiffer
Max Planck Institute for Infection Biology, Chariteplatz 1, D 10117 Berlin, Germany
Mol Microbiol 66:1174-91. 2007..This study identifies the first regulatory RNA of an enterobacterial pathogenicity island, and new roles for Hfq and HilD in SPI-1 gene expression... - Helicobacter pylori induces AGS cell motility and elongation via independent signaling pathwaysStefan Moese
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany
Infect Immun 72:3646-9. 2004..The cag pathogenicity island appears to be nonessential for induction of motility, whereas the elongation phenotype depends on translocation and phosphorylation of CagA... - Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosisUlrich E Schaible
Max Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 21 22, D 10117 Berlin, Germany
Nat Med 9:1039-46. 2003.... - The Helicobacter pylori CagA protein disrupts matrix adhesion of gastric epithelial cells by dephosphorylation of vinculinStefan Moese
Department of Molecular Biology, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany
Cell Microbiol 9:1148-61. 2007..We hypothesize that CagA-mediated inactivation of vinculin is a key step in the mechanism by which H. pylori induces damage to the gastric epithelium and represents an important step in disease development... - Human neutrophils kill Bacillus anthracisAnne Mayer-Scholl
Department of Cellular Microbiology, Max-Planck-Institute for Infection Biology, Berlin, Germany
PLoS Pathog 1:e23. 2005..anthracis infections, and that alpha-defensins play an important role in the potent anti-B. anthracis activity of neutrophils... - Role of interleukin-12 in determining differential kinetics of invariant natural killer T cells in response to differential burden of Listeria monocytogenesYoshiko Emoto
Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, 3 39 22 Showa machi, Maebashi, Gunma 371 8511, Japan
Microbes Infect 10:224-32. 2008..Our results indicate that NK1.1 surface expression on iNKT cells is differentially modulated by the burden of infection, and suggest that a high bacterial load probably causes loss of IL-12 production... - Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosisFlorian Winau
Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, 10117 Berlin, Germany
Immunity 24:105-17. 2006..tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis...