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. Skenteris NT, Luttermann E, Nair S, Evangelakos I, Pujantell M, Eggers M, Hausmann F, Bérouti M, Padoan B, Flomm FJ, Claussen JM, Grünhagel B, Salfelder A, Beifuss B, Biskup S, Blümke P, Rading K, Hildebrandt H, Matschl U, Giesemann-Jansen S, Hennesen J, Nikolaev VO, Kutsche M, Kubisch C, Koch-Nolte F, Tomas NM, Tolosa E, Lütgehetmann M, Stahl FR, Hornung V, Bunders MJ, Schlein C, Topf M, Kötter I, Altfeld M. Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome. JCI Insight. 2026 Feb 23;11(4):e187422.
2. Winterberg KJ, Schwentner V, Gu F, Möckl F, Li G, Bauche A, Etzold S, Rosche A, Weiß M, Thuille N, Förster F, Woelk L, Werner R, Kovacevic D, Fehse B, Kurelic R, Nawrocki M, Huber S, Mittrücker HW, Meier C, Müller CE, Baier G, Skålhegg BS, de Deken X, Wahl-Schott C, Mair T, Siebels B, Cugota Canals R, Odoardi F, Lodygin D, Flügel A, Nikolaev VO, Diercks BP, Guse AH. Multiple signaling events are required for NAADP synthesis by DUOX2 and formation of Ca²⁺ microdomains to initiate T cell activation. Sci Signal. 2026 Jan 13;19(920):eadp4326.
3. Kurelić R, Bielenberg M, Nikolaev VO. Monitoring Dynamic of cAMP Signaling in Primary Murine CD4⁺T Cells via Live-Cell Imaging. Methods Mol Biol. 2025;2904:115-124
4. Bielenberg M, Kurelic R, Frantz S, Nikolaev VO. A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation. Front Immunol. 2024 Mar 8;15:1365484. 
5. Karunakaran MM, Subramanian H, Jin Y, Mohammed F, Kimmel B, Juraske C, Starick L, Nöhren A, Länder N, Willcox CR, Singh R, Schamel WW, Nikolaev VO, Kunzmann V, Wiemer AJ, Willcox BE, Herrmann T. A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing. Nat Commun. 2023 Nov 22;14(1):7617. 
6. 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.
7. 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
8. 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
9. 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.
10. 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.

 

 

 

 

Prof. Dr. Manuel Alexander Friese

Selected publications (*equal contribution)

1. Sonner JK, Kahn A, Binkle-Ladisch L, Engler JB, Haack B, Zeiler C, Unger L, Bauer S, Fischbach F, Almanzar G, Walkenhorst M, Mayer C, Kolakowska A, Graute S, Ramien C, Winschel I, Rothammer N, Heine M, Horneffer-van der Sluis V, Thiemann V, Vieira V, Meurs N, Renné T, Prelog M, Jørgensen SB, Seeley RJ, Diemert A, Arck PC, Gold SM, Heeren J, Wischhusen J, Friese MA. A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation. Nat Immunol. 2026 Mar;27(3):503-515. 
2. Woo MS, Brand J, Bal LC, Moritz M, Walkenhorst M, Vieira V, Ipenberg I, Rothammer N, Wang M, Dogan B, Loreth D, Mayer C, Nagel D, Wagner I, Pfeffer LK, Landgraf P, van Ham M, Mattern KM, Winschel I, Frantz N, Sonner JK, Grosshans HK, Miguela A, Bauer S, Meurs N, Müller A, Binkle-Ladisch L, Salinas G, Jänsch L, Dieterich DC, Riedner M, Krüger E, Heppner FL, Glatzel M, Puelles VG, Engler JB, Nyengaard JR, Misgeld T, Kerschensteiner M, Merkler D, Meyer-Schwesinger C, Friese MA. The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis. Cell. 2025 Aug 21;188(17):4567-4585.e32. 
3. Schubert C, Schulz K, Sonner JK, Hadjilaou A, Seemann AL, Gierke J, Vieira V, Meurs N, Woo MS, Lohr C, Morellini F, Hirnet D, Friese MA. Neuroinflammation causes mitral cell dysfunction and olfactory impairment in a multiple sclerosis model. J Neuroinflammation. 2025 Mar 8;22(1):71. 
4. Woo MS, Mayer C, Binkle-Ladisch L, Sonner JK, Rosenkranz SC, Shaposhnykov A, Rothammer N, Tsvilovskyy V, Lorenz SM, Raich L, Bal LC, Vieira V, Wagner I, Bauer S, Glatzel M, Conrad M, Merkler D, Freichel M, Friese MA. STING orchestrates the neuronal inflammatory stress response in multiple sclerosis. Cell. 2024 Jul 25;187(15):4043-4060.e30. 
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.

Our Team

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