A16

A16

Multiple sclerosis (MS) is the most frequent inflammatory disease of the central nervous system (CNS) also resulting in olfactory deficits. However, underlying mechanisms are not understood. The adenine nucleotide axis has a crucial role in regulation of neuro-glia communication and inflammation and thereby qualifies as an attractive switchboard for both. Using the EAE inflammation model we aim to profile the cellular vulnerability and molecular determinants of neurodegeneration in the olfactory bulb and to elucidate the role of the P2Y1R and related P2 receptors in astrocyte-neuron interaction under homeostatic and inflammatory conditions and test their neuroprotective therapeutic potential.

Dr. Daniela Hirnet

Selected publications (*equal contribution)

 

1. 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. 
2. Wendlandt M, Kürten AJ, Beiersdorfer A, Schubert C, Samad-Yazdtchi K, Sauer J, Pinto MC, Schulz K, Friese MA, Gee CE, Hirnet D, Lohr C. A_2A adenosine receptor-driven cAMP signaling in olfactory bulb astrocytes is unaffected in experimental autoimmune encephalomyelitis. Front Immunol. 2023 Nov 23;14:1273837.
3. Hassani Nia F, Woike D, Bento I, Niebling S, Tibbe D, Schulz K, Hirnet D, Skiba M, Hönck HH, Veith K, Günther C, Scholz T, Bierhals T, Driemeyer J, Bend R, Failla AV, Lohr C, Alai MG, Kreienkamp HJ. Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans. Mol Psychiatry. 2024 Jun;29(6):1683-1697. 
4. Schubert C, Schulz K, Träger S, Plath AL, Omriouate A, Rosenkranz SC, Morellini F, Friese MA, Hirnet D. Neuronal Adenosine A₁ Receptor is Critical for Olfactory Function but Unable to Attenuate Olfactory Dysfunction in Neuroinflammation. Front Cell Neurosci. 2022 Jun 30;16:912030. 
5. Rotermund N, Winandy S, Fischer T, Schulz K, Fregin T, Alstedt N, Buchta M, Bartels J, Carlström M, Lohr C, Hirnet D (2018) Adenosine A1 receptor activates background potassium channels and modulates information processing in olfactory bulb mitral cells. J Physiol 596(4):717-733.
6. Schulz K, Rotermund N, Grzelka K, Benz J, Lohr C, Hirnet D (2018) Adenosine A1 Receptor-Mediated Attenuation of Reciprocal Dendro-Dendritic Inhibition in the Mouse Olfactory Bulb. Front Cell Neurosci 11:435.
7. Fischer T, Rotermund N, Lohr C, Hirnet D. P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb. Purinergic Signal. 2012 Jun;8(2):191-8. 
8. Thyssen A, Hirnet D*, Wolburg H, Schmalzing G, Deitmer JW, Lohr C (2010) Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling. Proc Natl Acad Sci USA107:15258-15263. *equal contribution as first authors
9. Doengi M, Hirnet D, Coulon P, Pape HC, Deitmer JW, Lohr C (2009) GABA uptake-dependent Ca(2+) signaling in developing olfactory bulb astrocytes. Proc Natl Acad Sci USA 106:17570-17575.
10. De Saint Jan D, Hirnet D, Westbrook GL, Charpak S (2009) External tufted cells drive the output of olfactory bulb glomeruli. J Neurosci 29:2043-2052.

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.

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PROPOSED PI 3RD FUNDING PERIOD

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