GRK 2098:  Biomedicine of the acid sphingomyelinase/acid ceramidase system

• Subject Area: Medicine
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259317790

• Final Report Year: 2020

Final Report Abstract

The present Graduiertenkolleg/Research Training Grant (GRK 2098/RTG 2098) focused on the biomedicine of sphingolipids. Sphingolipids are central to many fundamental cellular processes such as proliferation, differentiation and cell death, but also play an important role in bacterial and viral infections, cystic fibrosis, pneumonia, multiple sclerosis, cardiovascular diseases, cancer, major depression, neuro-degenerative diseases, or macular degeneration to name a few examples. The RTG 2098 focused on the role of sphingolipids in infectious biology, immunology, autoimmune syndroms, cancer and cardiovascular diseases. The projects focused strictly on the acid sphingomyelinase/ceramide/acid ceramidase/sphingosine/ sphingosine kinase/sphingosine 1-phosphate (S1P) pathway. The RTG provided training for PhD, MD/PhD, MD, and high school students in these emerging fields of the biomedicine of sphingolipids. One of the highlights of the RTG 2098 demonstrated a novel function of sphingosine as anti-viral defense mechanism in multivesicular bodies targeting viruses to lysosomal degradation. These studies describing a novel and principle role of sphingolipids in infectious biology were published in Nature Communications. A second highlight is the finding that expression of the acid sphingomyelinase is part of the defense against Citrobacter rodentium and that deficiency of the acid sphingomyelinase results in an overwhelming infection and an uncontrolled inflammatory Th1 and Th17 response, collectively triggering severe colitis. The studies were published in Front. Immunol. In line with a protective role of the acid sphingomyelinase in infections are the findings that a Tlymphocytes-specific overexpression of the acid sphingomyelinase reduced parasitemia during Plasmodium yoelii infection. The studies were also published in Front. Immunol. Further studies on the role of the acid sphingomyelinase in the immune system revealed that this enyzme controls activation and proliferation of CD4 T cells and the number of regulatory T cells in vivo. In accordance with increased numbers of immunosuppressive regulatory T cells in acid sphingomyelinase-deficient mice, members of the RTG 2098 showed that inhibition of the acid sphingomyelinase prevented the development of an auto-immune arthritis. These findings are consistent with a downregulation of an overshooting immune response upon inhibition of the acid sphingomyelinase. On the other hand, consumption of ceramide to sphingosine 1-phosphate was shown by studies within the RTG 2098 to promote influx of pro-inflammatory immune cells into the orbita in Graves' Orbitopathy. These studies were published in Thyroid and Invest. Ophthalmol. Vis. Sci. Collectively, the studies demonstrate that the balance between ceramide, sphingosine and sphingosine 1-phosphate plays an important role in the response of the immune system to bacteria, viruses and parasites. Another highlight of the RTG 2098 identified a novel role of sphingolipids in vasculogenesis after stroke and demonstrated that functional inhibitors of the acid sphingomyelinase promote vasculogenesis after ischemic stroke. Additional studies within the RTG 2098 demonstrated a role of the acid sphingomyelinase in tumor metastasis, in activation of macrophages upon infection with mycobacteria and the pathogenicity of toxins. Basic studies investigated the role of sphingosine 1-phosphate and its receptors in the development of aortic aneurysms, cholesterol efflux and cholesterol trafficking. The teaching program of the RTG focused on a specific and extensive training in sphingolipid biology and biomedicine. We offered the students a great variety of teaching instruments includingregular presentations, seminars, research days, discussion of the thesis, participation on many scientific meetings and research stays in partner laboratories in New York.

Publications

• (2015) Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS. J Neuroinflammation 12:234
  Schrewe L, Lill CM, Liu T, Salmen A, Gerdes LA, Guillot-Noel L, Akkad DA, Blaschke P, Graetz C, Hoffjan S, Kroner A, Demir S, Böhme A, Rieckmann P, ElAli A, Hagemann N, Hermann DM, Cournu-Rebeix I, Zipp F, Kümpfel T, Buttmann M, Zettl UK, Fontaine B, Bertram L, Gold R, Chan A
  (See online at https://doi.org/10.1186/s12974-015-0429-y)
• (2015) LDL suppresses angiogenesis through disruption of the HIF pathway via NF-κB inhibition which is reversed by the proteasome inhibitor BSc2118. Oncotarget 6:30251-62
  Yao G, Zhang Q, Doeppner TR, Niu F, Li Q, Yang Y, Kuckelkorn U, Hagemann N, Li W, Hermann DM, Dai Y, Zhou W, Jin F
  (See online at https://doi.org/10.18632/oncotarget.4943)
• (2016) Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System. Neurosignals 24:48-58
  Hoehn R, Monse M, Pohl E, Wranik S, Wilker B, Keitsch S, Soddemann M, Kornhuber J, Kohnen M, Edwards MJ, Grassmé H, Gulbins E
  (See online at https://doi.org/10.1159/000442611)
• (2016) Role of acid-sphingomyelinase-induced signaling in melanoma cells for hematogenous tumor metastasis. Cell Physiol Biochem 38:1-14
  Carpinteiro A, Beckmann N, Seitz A, Hessler G, Wilker B, Soddemann M, Helfrich I, Edelmann B, Gulbins E, Becker KA
  (See online at https://doi.org/10.1159/000438604)
• (2016) Role of Janus-Kinases in Major Depressive Disorder. Neurosignals 24:71-80
  Gulbins A, Grassmé H, Hoehn R, Kohnen M, Edwards MJ, Kornhuber J, Gulbins E
  (See online at https://doi.org/10.1159/000442613)
• (2016) Sphingomyelinase, Acidic. Encyclopedia of Signaling Molecules, 2nd edition. New York: Springer
  Beckmann N, Gulbins E, Becker KA, Carpinteiro A
  (See online at https://doi.org/10.1007/978-1-4614-6438-9_101873-1)
• (2016). Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+Foxp3+ regulatory T cells. Immunology 148:197-205
  Abel S, Ueffing K, Tatura R, Hutzler M, Hose M, Matuschewski K, Kehrmann J, Westendorf AM, Buer J, Hansen W
  (See online at https://doi.org/10.1111/imm.12602)
• (2017) 3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy. J Cereb Blood Flow Metab 37:3355-3367
  Lugo-Hernandez E, Squire A, Hagemann N, Brenzel A, Sardari M, Schlechter J, Sanchez- Mendoza EH, Gunzer M, Faissner A, Hermann DM
  (See online at https://doi.org/10.1177/0271678x17698970)
• (2017) 3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy. J Cereb Blood Flow Metab 37:3355-3367
  Lugo-Hernandez E, Squire A, Hagemann N, Brenzel A, Sardari M, Schlechter J, Sanchez- Mendoza EH, Gunzer M, Faissner A, Hermann DM
  (See online at https://doi.org/10.1177/0271678x17698970)
• (2017) DC-Derived IL-10 Modulates Pro-inflammatory Cytokine Production and Promotes Induction of CD4+IL-10+ Regulatory T Cells during Plasmodium yoelii Infection. Front Immunol 8:152
  Loevenich K, Ueffing K, Abel S, Hose M, Matuschewski K, Westendorf AM, Buer J, Hansen W
  (See online at https://doi.org/10.3389/fimmu.2017.00152)
• (2017) DC-Derived IL-10 Modulates Pro-inflammatory Cytokine Production and Promotes Induction of CD4+IL-10+ Regulatory T Cells during Plasmodium yoelii Infection. Front Immunol 8:152
  Loevenich K, Ueffing K, Abel S, Hose M, Matuschewski K, Westendorf AM, Buer J, Hansen W
  (See online at https://doi.org/10.3389/fimmu.2017.00152)
• (2017) Direct pharmacological targeting of a mitochondrial ion channel selectively kills tumor cells in vivo. Cancer Cell 31:516-531
  Leanza L, Romio M, Becker KA, Azzolini M, Trentin L, Managò A, Venturini E, Zaccagnino A, Mattarei A, Carraretto L, Urbani A, Kadow S, Biasutto L, Martini V, Severin F, Peruzzo R, Trimarco V, Egberts JH, Hauser C, Visentin A, Semenzato G, Kalthoff H, Zoratti M, Gulbins E, Paradisi C, Szabo I
  (See online at https://doi.org/10.1016/j.ccell.2017.03.003)
• (2017) Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis Lungs. Cell Physiol Biochem 41:1208-1218
  Kovacic B, Sehl C, Wilker B, Kamler M, Gulbins E, Becker KA
  (See online at https://doi.org/10.1159/000464382)
• (2017) Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer. PLoS Pathog 13:e1006649
  Pastille E, Frede A, McSorley HJ, Gräb J, Adamczyk A, Kollenda S, Hansen W, Epple M, Buer J, Maizels RM, Klopfleisch R, Westendorf AM
  (See online at https://doi.org/10.1371/journal.ppat.1006649)
• (2017) Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis. Nat Commun 8:1597
  Krzywinska E, Kantari-Mimoun C, Kerdiles Y, Sobecki M, Isagawa T, Gotthardt D, Castells M, Haubold J, Millien C, Viel T, Tavitian B, Takeda N, Fandrey J, Vivier E, Sexl V, Stockmann C
  (See online at https://doi.org/10.1038/s41467-017-01599-w)
• (2017) Melanoma cell metastasis via P-selectin-mediated activation of acid sphingomyelinase in platelets. Clin Exp Metastasis 34:25-35
  Becker KA, Beckmann N, Adams C, Hessler G, Kramer M, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.1007/s10585-016-9826-6)
• (2017) Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by Sphingosine. Cell Physiol Biochem 43:1603-1616
  Becker KA, Li X, Seitz A, Steinmann J, Koch A, Schuchman E, Kamler M, Edwards MJ, Caldwell CC, Gulbins E
  (See online at https://doi.org/10.1159/000482024)
• (2017) Presentation of Autoantigen in Peripheral Lymph Nodes Is Sufficient for Priming Autoreactive CD8+ T Cells. Front Immunol 8:113
  Honke N, Shaabani N, Teijaro JR, Christen U, Hardt C, Bezgovsek J, Lang PA, Lang KS
  (See online at https://doi.org/10.3389/fimmu.2017.00113)
• (2017) Regulation of Arthritis Severity by the Acid Sphingomyelinase. Cell Physiol Biochem 43:1460-1471
  Beckmann N, Becker KA, Walter S, Becker JU, Kramer M, Hessler G, Weber S, Göthert JR, Fassbender K, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.1159/000481968)
• (2017) Staphylococcus aureus Alpha-Toxin Disrupts Endothelial-Cell Tight Junctions via Acid Sphingomyelinase and Ceramide. Infect Immun 86:e00606-17
  Becker KA, Fahsel B, Kemper H, Mayeres J, Li C, Wilker B, Keitsch S, Soddemann M, Sehl C, Kohnen M, Edwards MJ, Grassmé H, Caldwell CC, Seitz A, Fraunholz M, Gulbins E
  (See online at https://doi.org/10.1128/iai.00606-17)
• (2017) Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia. 85: e00883-16
  Li C, Wu Y, Riehle A, Ma J, Kamler M, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1128/iai.00883-16)
• (2017) Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia. Infect Immun 85:e00883-16
  Li C, Wu Y, Riehle A, Ma J, Kamler M, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1128/iai.00883-16)
• (2017) Staphylococcus aureus α-Toxin Induces Inflammatory Cytokines via Lysosomal Acid Sphingomyelinase and Ceramides. Cell Physiol Biochem 43:2170-2184
  Ma J, Gulbins E, Edwards MJ, Caldwell CC, Fraunholz M, Becker KA
  (See online at https://doi.org/10.1159/000484296)
• (2017) β1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections. Cell Hist Microbe 21:707-718
  Grassmé H, Henry B, Ziobro R, Becker KA, Riethmüller J, Gardner A, Seitz AP, Steinmann J, Lang S, Ward C, Schuchman EH, Caldwell CC, Kamler M, Edwards MJ, Brodlie M, Gulbins E
  (See online at https://doi.org/10.1016/j.chom.2017.05.001)
• (2018) Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide. Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide. Mol Psychiatry 23:2324-2346
  Gulbins A, Schumacher F, Becker KA, Wilker B, Soddemann M, Boldrin F, Müller CP, Edwards MJ, Goodman M, Caldwell CC, Kleuser B, Kornhuber J, Szabo I, Gulbins E
  (See online at https://doi.org/10.1038/s41380-018-0090-9)
• (2018) CD40 Enhances Sphingolipids in Orbital Fibroblasts: Potential Role of Sphingosine-1-Phosphate in Inflammatory T-Cell Migration in Graves' Orbitopathy. Invest Ophthalmol Vis Sci 59:5391-5397
  Plöhn S, Edelmann B, Japtok L, He X, Hose M, Hansen W, Schuchman EH, Eckstein A, Berchner-Pfannschmidt U
  (See online at https://doi.org/10.1167/iovs.18-25466)
• (2018) CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection. Nat Commun 9:2561
  Khairnar V, Duhan V, Patil AM, Zhou F, Bhat H, Thoens C, Sharma P, Adomati T, Friendrich SK, Bezgovsek J, Dreesen JD, Wennemuth G, Westendorf AM, Zelinskyy G, Dittmer U, Hardt C, Timm J, Göthert JR, Lang PA, Singer BB, Lang KS
  (See online at https://doi.org/10.1038/s41467-018-04832-2)
• (2018) CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection. Nat Commun 9:2561
  Khairnar V, Duhan V, Patil AM, Zhou F, Bhat H, Thoens C, Sharma P, Adomati T, Friendrich SK, Bezgovsek J, Dreesen JD, Wennemuth G, Westendorf AM, Zelinskyy G, Dittmer U, Hardt C, Timm J, Göthert JR, Lang PA, Singer BB, Lang KS
  (See online at https://doi.org/10.1038/s41467-018-04832-2)
• (2018) Crosstalk Between Sphingomyelinases and Reactive Oxygen Species in Mycobacterial Infection. Antioxid Redox Signal 28:935-948
  Wu Y, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1089/ars.2017.7050)
• (2018) Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self-tolerance for a murine model of autoimmune thyroid disease and Graves' orbitopathy. Clin Exp Immunol 191:255-267
  Schlüter A, Horstmann M, Diaz-Cano S, Plöhn S, Stähr K, Mattheis S, Oeverhaus M, Lang S, Flögel U, Berchner-Pfannschmidt U, Eckstein A, Banga JP
  (See online at https://doi.org/10.1111/cei.13075)
• (2018) Graves' orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model. Sci Rep 8:13096
  Schlüter A, Flögel U, Diaz-Cano S, Görtz GE, Stähr K, Oeverhaus M, Plöhn S, Mattheis S, Moeller LC, Lang S, Bechrakis NE, Banga JP, Eckstein A, Berchner-Pfannschmidt U
  (See online at https://doi.org/10.1038/s41598-018-31253-4)
• (2018) Graves' orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model. Sci Rep 8:13096
  Schlüter A, Flögel U, Diaz-Cano S, Görtz GE, Stähr K, Oeverhaus M, Plöhn S, Mattheis S, Moeller LC, Lang S, Bechrakis NE, Banga JP, Eckstein A, Berchner-Pfannschmidt U
  (See online at https://doi.org/10.1038/s41598-018-31253-4)
• (2018) High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation. Angiogenesis 21:381-394
  Jin F, Hagemann N, Sun L, Wu J, Doeppner TR, Dai Y, Hermann DM
  (See online at https://doi.org/10.1007/s10456-018-9603-z)
• (2018) Mycobacterial Infection is Promoted by Neutral Sphingomyelinase 2 Regulating a Signaling Cascade Leading to Activation of β1-Integrin. Cell Physiol Biochem 51:1815-1829
  Wu Y, Li C, Riehle A, Pollmeier B, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1159/000495683)
• (2018) Pathological manifestations of Farber disease in a new mode model. Biol Chem 399:1183-1202
  Beckmann N, Kadow S, Schumacher F, Göthert JR, Kesper S, Draeger A, Schulz- Schaeffer WJ, Wang J, Becker JU, Kramer M, Kühn C, Kleuser B, Becker KA, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.1515/hsz-2018-0170)
• (2018) Regulation of Staphylococcus aureus Infection of Macrophages by CD44, Reactive Oxygen Species, and Acid Sphingomyelinase Antioxid Redox Signal 28:916-934
  Li C, Wu Y, Riehle A, Orian-Rousseau V, Zhang Y, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1089/ars.2017.6994)
• (2018) Regulation of Staphylococcus aureus Infection of Macrophages by CD44, Reactive Oxygen Species, and Acid Sphingomyelinase. Antioxid Redox Signal 28:916-934
  Li C, Wu Y, Riehle A, Orian-Rousseau V, Zhang Y, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1089/ars.2017.6994)
• (2018) Sphingolipids in early viral replication and innate immune activation. Biol Chem 399:1115-1123. Review
  Bezgovsek J, Gulbins E, Friedrich SK, Lang KS, Duhan V
  (See online at https://doi.org/10.1515/hsz-2018-0181)
• (2018) Sphingolipids in inflammatory hypoxia. Biol Chem 399:1169-1174. Review
  Glaser UG, Fandrey J
  (See online at https://doi.org/10.1515/hsz-2018-0173)
• (2018) Structural basis of sterol binding and transport by a yeast StARkin domain. J Biol Chem 293:5522-5531
  Jentsch JA, Kiburu I, Pandey K, Timme M, Ramlall T, Levkau B, Wu J, Eliezer D, Boudker O, Menon AK
  (See online at https://doi.org/10.1074/jbc.ra118.001881)
• (2018) The function of sphingomyelinases in mycobacterial infections. Biol Chem 399:1125-1133. Review
  Wu Y, Gulbins E, Grassmé H
  (See online at https://doi.org/10.1515/hsz-2018-0179)
• Role of acid sphingomyelinase in T lymphocyte activation, Dissertation, 2018
  Begum, Salina
  
• The characterization of immune cells in Asm-overexpressed mice, Dissertation, 2018
  Hung, Wing Yee
  
• (2019 )Signalling Effects Induced by Acid Ceramidase in Human Epithelial Or Leukemic Cell Lines. Cell Physiol Biochem 52:1092-1102
  Baduva K, Büchter L, Kreyenkamp K, Westphal L, Wilker B, Kohnen M, Schuchman EH, Edwards MJ, Becker KA, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.33594/000000074)
• (2019) Acid Sphingomyelinase Deficiency Ameliorates Farber Disease. Int J Mol Sci 20:6253
  Beckmann N, Becker KA, Kadow S, Schumacher F, Kramer M, Kühn C, Schulz-Schaeffer WJ, Edwards MJ, Kleuser B, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.3390/ijms20246253)
• (2019) Acid Sphingomyelinase-Ceramide System in Bacterial Infections. Cell Physiol Biochem 52:280-301. Review
  Li C, Wang A, Wu Y, Gulbins E, Grassmé H, Zhao Z
  (See online at https://doi.org/10.33594/000000021)
• (2019) Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice. Bone 125:1-7
  Weske S, Vaidya M, von Wnuck Lipinski K, Keul P, Manthe K, Burkhart C, Haberhauer G, Heusch G, Levkau B
  (See online at https://doi.org/10.1016/j.bone.2019.04.015)
• (2019) Fingolimod Improves the Outcome of Experimental Graves' Disease and Associated Orbitopathy by Modulating the Autoimmune Response to the Thyroid-Stimulating Hormone Receptor. Thyroid 29:1286-1301
  Plöhn S, Hose M, Schlüter A, Michel L, Diaz-Cano S, Hendgen-Cotta UB, Banga JP, Bechrakis NE, Hansen W, Eckstein A, Berchner-Pfannschmidt U
  (See online at https://doi.org/10.1089/thy.2018.0754)
• (2019) Fingolimod Improves the Outcome of Experimental Graves' Disease and Associated Orbitopathy by Modulating the Autoimmune Response to the Thyroid-Stimulating Hormone Receptor. Thyroid 29:1286-1301
  Plöhn S, Hose M, Schlüter A, Michel L, Diaz-Cano S, Hendgen-Cotta UB, Banga JP, Bechrakis NE, Hansen W, Eckstein A, Berchner-Pfannschmidt U
  (See online at https://doi.org/10.1089/thy.2018.0754)
• (2019) Inhibition of PI-3-K and AKT Amplifies Kv1.3 Inhibitor- Induced Death of Human T Leukemia Cells. Cell Physiol Biochem 53:1-10
  Bergermann T, Born L, Ferguson F, Latkovic P, Scheul A, Sonnenschein N, Leanza L, Keitsch S, Sehl C, Wilker B, Edwards MJ, Zoratti M, Paradisi C, Kohnen M, Szabo I, Becker KA, Carpinteiro A
  (See online at https://doi.org/10.33594/000000187)
• (2019) Interferon in the CNS. Neurosignals 27:44-53. Review
  Bhat H, Lang KS, Hardt C, Lang J
  (See online at https://doi.org/10.33594/000000197)
• (2019) Intestinal acid sphingomyelinase protects from severe pathogendriven colitis. Front Immunol 10:1386
  Meiners J, Palmieri V, Klopfleisch R, Ebel JF, Japtok L, Schumacher F, Yusuf AM, Becker KA, Zöller J, Hose M, Kleuser B, Hermann DM, Kolesnick RN, Buer J, Hansen W, Westendorf AM
  (See online at https://doi.org/10.3389/fimmu.2019.01386)
• (2019) Mechanisms of lymphatic system-specific viral replication and its potential role in autoimmune disease. Clin Exp Immunol 195:64-73. Review
  Friedrich SK, Lang PA, Friebus-Kardash J, Duhan V, Bezgovsek J, Lang KS
  (See online at https://doi.org/10.1111/cei.13241)
• (2019) MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation. J Autoimmun 96:94-103
  Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J, Hansen W
  (See online at https://doi.org/10.1016/j.jaut.2018.08.010)
• (2019) NK cell-intrinsic FcεRIγ limits CD8+ T-cell expansion and thereby turns an acute into a chronic viral infection. PLoS Pathog 15:e1007797
  Duhan V, Hamdan TA, Xu HC, Shinde P, Bhat H, Li F, Al-Matary Y, Häussinger D, Bezgovsek J, Friedrich SK, Hardt C, Lang PA, Lang KS
  (See online at https://doi.org/10.1371/journal.ppat.1007797)
• (2019) Potent anti-inflammatory properties of HDL in vascular smooth muscle cells mediated by HDL-S1P and their impairment in coronary artery disease due to lower HDL- S1P: a new aspect of HDL dysfunction and its therapy. FASEB J 33:1482-1495
  Keul P, Polzin A, Kaiser K, Gräler M, Dannenberg L, Daum G, Heusch G, Levkau B
  (See online at https://doi.org/10.1096/fj.201801245r)
• (2019) Potent anti-inflammatory properties of HDL in vascular smooth muscle cells mediated by HDL-S1P and their impairment in coronary artery disease due to lower HDL-S1P: a new aspect of HDL dysfunction and its therapy. FASEB J 33:1482-1495
  Keul P, Polzin A, Kaiser K, Gräler M, Dannenberg L, Daum G, Heusch G, Levkau B
  (See online at https://doi.org/10.1096/fj.201801245r)
• (2019) Regulation of ABCA1-mediated cholesterol efflux by sphingosine-1-phosphate signaling in macrophages. J Lipid Res 60:506-515
  Vaidya M, Jentsch JA, Peters S, Keul P, Weske S, Gräler MH, Mladenov E, Iliakis G, Heusch G, Levkau B
  (See online at https://doi.org/10.1194/jlr.m088443)
• (2019) Regulation of ABCA1-mediated cholesterol efflux by sphingosine-1-phosphate signaling in macrophages. J Lipid Res 60:506-515
  Vaidya M, Jentsch JA, Peters S, Keul P, Weske S, Gräler MH, Mladenov E, Iliakis G, Heusch G, Levkau B
  (See online at https://doi.org/10.1194/jlr.m088443)
• (2019) T cell-specific overexpression of acid sphingomyelinase results in elevated T cell activation and reduced parasite burden during Plasmodium yoelii infection. Front Immunol 10:1225
  Hose M, Günther A, Abberger H, Begum S, Korencak M, Becker KA, Buer J, Westendorf AM, Hansen W
  (See online at https://doi.org/10.3389/fimmu.2019.01225)
• (2019) Tamoxifen Protects from Vesicular Stomatitis Virus Infection. Pharmaceuticals (Basel) 12:142
  Cham LB, Friedrich SK, Adomati T, Bhat H, Schiller M, Bergerhausen M, Hamdan T, Li F, Machlah YM, Ali M, Duhan V, Lang KS, Friebus-Kardash J, Bezgovsek J
  (See online at https://doi.org/10.3390/ph12040142)
• (2019) The Acid Sphingomyelinase/ Ceramide System as Target for Ischemic Stroke Therapies. Neurosignals 27:32-43. Review
  Mohamud Yusuf A, Hagemann N, Hermann DM
  (See online at https://doi.org/10.33594/000000184)
• (2019) The IL-33/ST2 pathway shapes the regulatory T cell phenotype to promote intestinal cancer. Mucosal Immunol 12:990-1003
  Pastille E, Wasmer MH, Adamczyk A, Vu VP, Mager LF, Phuong NNT, Palmieri V, Simillion C, Hansen W, Kasper S, Schuler M, Muggli B, McCoy KD, Buer J, Zlobec I, Westendorf AM, Krebs P
  (See online at https://doi.org/10.1038/s41385-019-0176-y)
• (2019) Validity and Reliability of Neurological Scores in Mice Exposed to Middle Cerebral Artery Occlusion. Stroke 50:2875-2882
  Bieber M, Gronewold J, Scharf AC, Schuhmann MK, Langhauser F, Hopp S, Mencl S, Geuss E, Leinweber J, Guthmann J, Doeppner TR, Kleinschnitz C, Stoll G, Kraft P, Hermann DM
  (See online at https://doi.org/10.1161/strokeaha.119.026652)
• Analyse des Einflusses der sauren Sphingomyelinase auf T-Zell- Antworten während Tumorentwicklung und Plasmodium-Infektion, Dissertation, 2019
  Hose, Matthias
  (See online at https://doi.org/10.17185/duepublico/70289)
• Characterization of lungs in a transgenic acid sphingomyelinase mouse model, Dissertation, 2019
  Koch, Anne
  (See online at https://doi.org/10.17185/duepublico/70537)
• Der Einfluss von Sphingosin-1-Phosphat auf Hypoxie-induzierbare Faktoren im bestrahlten Tumormikromilieu, Dissertation, 2019
  Glaser, Ulrike Gesine
  (See online at https://doi.org/10.17185/duepublico/71420)
• The crucial role of sphingosine-1-phosphate and the therapeutic potential of fingolimod for Graves´ disease and associated orbitopathy, Dissertation, 2019
  Plöhn, Svenja
  (See online at https://doi.org/10.17185/duepublico/70079)
• The effect of the acid sphingomyelinase/ceramidase system on bacterial induced colitis, Dissertation, 2019
  Meiners, Jana
  (See online at https://doi.org/10.17185/duepublico/70151)
• The impact of S1P receptors on the high-density lipoprotein-mediated cholesterol efflux in Chinese hamster ovary cells, Dissertation, 2019
  Manthe, Kristina
  (See online at https://doi.org/10.17185/duepublico/70529)
• (2020) A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control. J Hepatol 72:960-975
  Namineni S, O'Connor T, Faure-Dupuy S, Johansen P, Riedl T, Liu K, Xu H, Singh I, Shinde P, Li F, Pandyra A, Sharma P, Ringelhan M, Muschaweckh A, Borst K, Blank P, Lampl S, Neuhaus K, Durantel D, Farhat R, Weber A, Lenggenhager D, Kündig TM, Staeheli P, Protzer U, Wohlleber D, Holzmann B, Binder M, Breuhahn K, Assmus LM, Nattermann J, Abdullah Z, Rolland M, Dejardin E, Lang PA, Lang KS, Karin M, Lucifora J, Kalinke U, Knolle PA, Heikenwalder M
  (See online at https://doi.org/10.1016/j.jhep.2019.12.019)
• (2020) Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease. Nat Commun 11:1338
  Lang J, Bohn P, Bhat H, Jastrow H, Walkenfort B, Cansiz F, Fink J, Bauer M, Olszewski D, Ramos-Nascimento A, Duhan V, Friedrich SK, Becker KA, Krawczyk A, Edwards MJ, Burchert A, Huber M, Friebus-Kardash J, Göthert JR, Hardt C, Probst HC, Schumacher F, Köhrer K, Kleuser B, Babiychuk EB, Sodeik B, Seibel J, Greber UF, Lang PA, Gulbins E, Lang KS
  (See online at https://doi.org/10.1038/s41467-020-15072-8)
• (2020) Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease. Nat Commun 11:1338
  Lang J, Bohn P, Bhat H, Jastrow H, Walkenfort B, Cansiz F, Fink J, Bauer M, Olszewski D, Ramos-Nascimento A, Duhan V, Friedrich SK, Becker KA, Krawczyk A, Edwards MJ, Burchert A, Huber M, Friebus-Kardash J, Göthert JR, Hardt C, Probst HC, Schumacher F, Köhrer K, Kleuser B, Babiychuk EB, Sodeik B, Seibel J, Greber UF, Lang PA, Gulbins E, Lang KS
  (See online at https://doi.org/10.1038/s41467-020-15072-8)
• (2020) CEACAM1 regulates CD8+ T cell immunity and protects from severe pathology during Citrobacter rodentium induced colitis. Gut Microbes 11:1790-1805
  Zöller J, Ebel JF, Khairnar V, Schmitt V, Klopfleisch R, Meiners J, Seiffart V, Hansen W, Buer J, Singer BB, Lang KS, Westendorf AM
  (See online at https://doi.org/10.1080/19490976.2020.1775464)
• (2020) Dead Cells Induce Innate Anergy via Mertk after Acute Viral Infection. Cell Rep 30:3671-3681
  Adomati T, Cham LB, Hamdan TA, Bhat H, Duhan V, Li F, Ali M, Lang E, Huang A, Naser E, Khairnar V, Friedrich SK, Lang J, Friebus-Kardash J, Bergerhausen M, Schiller M, Machlah YM, Lang F, Häussinger D, Ferencik S, Hardt C, Lang PA, Lang KS
  (See online at https://doi.org/10.1016/j.celrep.2020.02.101)
• (2020) Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection. Cell Rep 31:107494
  Cham LB, Torrez Dulgeroff LB, Tal MC, Adomati T, Li F, Bhat H, Huang A, Lang PA, Moreno ME, Rivera JM, Galkina SA, Kosikova G, Stoddart CA, McCune JM, Myers LM, Weissman IL, Lang KS, Hasenkrug KJ
  (See online at https://doi.org/10.1016/j.celrep.2020.03.058)
• (2020) Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection. Pathogens 9:96
  Hamdan TA, Bhat H, Cham LB, Adomati T, Lang J, Li F, Murtaza A, Hardt C, Lang PA, Duhan V, Lang KS
  (See online at https://doi.org/10.3390/pathogens9020096)
• (2020) Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Induce Ischemic Neuroprotection by Modulating Leukocytes and Specifically Neutrophils. Stroke 51:1825-1834
  Wang C, Börger V, Sardari M, Murke F, Skuljec J, Pul R, Hagemann N, Dzyubenko E, Dittrich R, Gregorius J, Hasenberg M, Kleinschnitz C, Popa-Wagner A, Doeppner TR, Gunzer M, Giebel B, Hermann DM
  (See online at https://doi.org/10.1161/strokeaha.119.028012)
• (2020) Prolyl hydroxylase domain 2 reduction enhances skeletal muscle tissue regeneration after soft tissue trauma in mice. PLoS One 15:e0233261
  Settelmeier S, Schreiber T, Mäki J, Byts N, Koivunen P, Myllyharju J, Fandrey J, Winning S
  (See online at https://doi.org/10.1371/journal.pone.0233261)
• (2020) Role of 1-Deoxysphingolipids in docetaxel neurotoxicity. J Neurochem 10.111
  Becker KA, Uerschels AK, Goins L, Doolen S, McQuerry KJ, Bielawski J, Sure U, Bieberich E, Taylor BK, Gulbins E, Spassieva SD
  (See online at https://doi.org/10.1111/jnc.14985)
• (2020) Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro. J Mol Med (Berl) 98(2):209-219
  Beck S, Sehl C, Voortmann S, Verhasselt HL, Edwards MJ, Buer J, Hasenberg M, Gulbins E, Becker KA
  (See online at https://doi.org/10.1007/s00109-019-01858-x)
• (2020) Ultrasmall gold nanoparticles (2 nm) can penetrate and enter cell nuclei in an in vitro 3D brain spheroid model. Acta Biomater 111:349-362
  Sokolova V, Nzou G, van der Meer SB, Ruks T, Heggen M, Loza K, Hagemann N, Murke F, Giebel B, Hermann DM, Atala AJ, Epple M
  (See online at https://doi.org/10.1016/j.actbio.2020.04.023)
• (2020) Usp18 Expression in CD169 + Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV. Vaccines (Basel) 8:142
  Friedrich SK, Schmitz R, Bergerhausen M, Lang J, Cham LB, Duhan V, Häussinger D, Hardt C, Addo M, Prinz M, Asano K, Lang PA, Lang KS
  (See online at https://doi.org/10.3390/vaccines8010142)
• (2020). A novel visible range FRET probe for monitoring acid sphingomyelinase activity in living cells. Chem Eur J 26: 5780-3
  Kappe C, Mohamed ZH, Naser E, Carpinteiro A, Arenz C
  (See online at https://doi.org/10.1002/chem.202000133)
• (2020). Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinasein vitro. J Lipid Res 61:896-910
  Naser E, Kadow S, Schumacher F, Mohamed ZH, Kappe C, Hessler G, Pollmeier B, Kleuser B, Arenz C, Becker KA, Gulbins E, Carpinteiro A
  (See online at https://doi.org/10.1194/jlr.ra120000682)
• Homozygous Smpd1 deficiency aggravates brain ischemia/reperfusioninjury by mechanisms involving polymorphonuclear neutrophils, whereas heterozygous Smpd1 deficiency protects against mild focal cerebralischemia". Basic Res. In Cardiology, Sept. 2020
  Hagemann, N; Yusuf, AM; Martiny, C; Zhang, X; Kleinschnitz, C; Gunzer, M; Kolesnick, RN, Erich Gulbins, Dirk M Hermann
  (See online at https://doi.org/10.1007/s00395-020-00823-x)
• The antiviral effector functions of sphingolipids, Dissertation, 2020
  Lang, Judith
  
• The role of IKKε in viral infection, Dissertation, 2020
  Li, Fanghui