A06

A06

3’,5’-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger with a pivotal role in immunomodulation. The formation and degradation of intracellular cAMP is regulated by diverse pathways. We will explore phosphodiesterase (PDE) 2A and natriuretic peptides (NP) and investigate how they mechanistically impact T cell function and contribute to neuroinflammation by modulating cAMP. Together with an unsupervised approach to discover GPCR(s) that control T cell activity, our research will provide an understanding of the molecular mechanisms that control cAMP levels in T cells that can potentially be exploited therapeutically.

Prof. Dr. Viacheslav O. Nikolaev

Selected publications (*equal contribution)

 

1. De Jong KA, Ehret S, Heeren J, Nikolaev VO. Live-cell imaging identifies cAMP microdomains regulating β-adrenoceptor-subtype-specific lipolytic responses in human white adipocytes. Cell Rep. 2023 May 30;42(5):112433.
2. Berisha F, Götz K, Wegener JW, Brandenburg S, Subramanian H, Molina CE, Rueffer A, Petersen J, Bernhardt A, Girdauskas E, Jungen C, Pape U, Kraft AE, Warnke S, Lindner D, Westermann D, Blankenberg S, Meyer C, Hasenfuß G, Lehnart SE, Nikolaev VO (2021) cAMP Imaging at Ryanodine Receptors Reveals β2-Adrenoceptor Driven Arrhythmias. Circ Res 129(1):81-94
3. Subramanian H, Froese A, Jönsson P, Schmidt H, Gorelik J, Nikolaev VO (2021) Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP. Nature Commun 9:2446
4. Sprenger JU, Perera RK, Steinbrecher JH, Lehnart SE, Maier LS, Hasenfuss G, Nikolaev VO (2015) In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease. Nature Commun 6:6965.
5. Perera RK, Sprenger JU, Steinbrecher JH, Hübscher D, Lehnart SE, Abesser M, Schuh K, ElArmouche A, Nikolaev VO (2015) Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-Induced augmentation of beta-adrenoceptor-stimulated contractility in early cardiac hypertrophy. Circ Res 116:1304-1311.
6. Götz KR, Sprenger JU, Perera RK, Steinbrecher JH, Lehnart SE, Kuhn M, Gorelik J, Balligand JL, Nikolaev VO (2014) Transgenic mice for real-time visualization of cGMP in intact adult cardiomyocytes. Circ Res 114:1235-1245.
7. Börner S, Schwede F, Schlipp A, Berisha F, Calebiro D, Lohse MJ, Nikolaev VO (2011) FRET measurements of intracellular cAMP concentrations and cAMP analog permeability in intact cells. Nature Protoc 6:427-438.
8. Nikolaev VO, Moshkov A, Lyon AR, Miragoli M, Novak P, Paur H, Lohse MJ, Korchev YE, Harding SE, Gorelik J. (2010) Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 327:1653-1657.
9. Calebiro D*, Nikolaev VO*, Gagliani MC, de Filippis T, Dees C, Tacchetti C, Persani L, Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7:e1000172.
10. Nikolaev VO, Gambaryan S, Lohse MJ (2006) Fluorescent sensors for rapid monitoring of intracellular cGMP. Nature Methods 3, 23-25. 

 

 

 

 

Prof. Dr. Manuel Alexander Friese

Selected publications (*equal contribution)

 

1. Winkler I, Engler JB, Vieira V, Bauer S, Liu YH, Di Liberto G, Grochowska KM, Wagner I, Bier J, Bal LC, Rothammer N, Meurs N, Egervari K, Schattling B, Salinas G, Kreutz MR, Huang YS, Pless O, Merkler D, Friese MA (2023) MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration. Sci Adv.;9(47):eadi6855.
2. Rothammer N, Woo MS, Bauer S, Binkle-Ladisch L, Di Liberto G, Egervari K, Wagner I, Haferkamp U, Pless O, Merkler D, Engler JB, Friese MA (2022) G9a dictates neuronal vulnerability to inflammatory stress via transcriptional control of ferroptosis. Sci Adv. 8(31):eabm5500.
3. Woo MS, Ufer F, Rothammer N, Di Liberto G, Binkle L, Haferkamp U, Sonner JK, Engler JB, Hornig S, Bauer S, Wagner I, Egervari K, Raber J, Duvoisin RM, Pless O, Merkler D, Friese MA (2021) Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation. J Exp Med 3;218(5):e20201290.
4. Kaufmann M, Evans H, Schaupp AL, Engler JB, Kaur G, Willing A, Kursawe N, Schubert C, Attfield KE, Fugger L, Friese MA (2021) Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis. Med 12;2(3):296-312.e8.
5. Schattling B, Engler JB, Volkmann C, Rothammer N, Woo MS, Petersen M, Winkler I, Kaufmann M, Rosenkranz SC, Fejtova A, Thomas U, Bose A, Bauer S, Träger S, Miller KK, Brück W, Duncan KE, Salinas G, Soba P, Gundelfinger ED, Merkler D, Friese MA (2019) Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. Nat Neurosci 22(6):887-896.
6. Engler JB, Kursawe N, Solano ME, Patas K, Wehrmann S, Heckmann N, Lühder F, Reichardt HM, Arck PC, Gold SM, Friese MA (2017) Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy. Proc Natl Acad Sci USA 114:E181-E190.
7. Ufer F, Vargas P, Engler JB, Tintelnot J, Schattling B, Winkler H, Bauer S, Kursawe N, Willing A, Keminer O, Ohana O, Salinas-Riester G, Pless O, Kuhl D, Friese MA (2016) Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation. Sci Immunol 1:eaaf8665.
8. Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Brück W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA (2012) TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 1805-1811.
9. Friese MA, Jakobsen KB, Friis L, Etzensperger R, Craner MJ, McMahon RM, Jensen LT, Huygelen V, Jones EY, Bell JI, Fugger L (2008) Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med 11:1227-1235.
10. Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, Fugger (2007) L. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nature Med 1483-1489.

Our Team