We are intested in the crossregulation of immune cells and peripheral sensory neurons during inflammatory processes leading to chronic pain states. We use a variety of methods ranging from biochemical, cell biological, imaging to behavioral approaches. These techniques include many state of the art approaches such as calcium imaging, Multi-Epitope-Ligand-Carthographie for multiple sequential immunohistochemistry as well as multiparameter FACS analysis.
The goal is to understand the fundamental mechanisms underlying the development and maintenance of chronic pain and to establish, based on the identified mechanisms, new treatment options. We primarily concentrate on lipid-activated G-protein coupled receptors (GPCRs) and their signaling pathways in the immunsystem and the peripheral nerve system. A strong focus is put on the translational aspects of our findings, which is supported by close collabotrations with the Fraunhofer IME groups located in Frankfurt and Hamburg, the Fraunhofer FIT in Bonn and the Max-Planck-Institute for Heart and Lung Research in Bad Nauheim. Together with these groups we pursue several projects including the development new imaging techniques and high throughput screenings for the identification of therapeutically interesting compounds.
Selected currently funded projects:
(1) Role of mast cells in resolution of inflammation (DFG, Graduateschool AVE),
(2) Platelet-macrophage interactions and their role in macrophage polarization in inflammatory pain models (DFG, SFB 1039),
(3) Functions of the ubiquitin ligase PAM in neuronal transmission and inflammatory processes (DFG),
(4) Immunsupression by receptors expressed in macrophages (Else Kröner Fresenius Stiftung, TRIP 2.0 Graduateschool),
(5) Prostanoid receptors in trauma- and tumor-induced neuropathic pain (Else Kröner Fresenius Stiftung, International Else Kröner Graduateschool)
Lipid measurements using LC-MS/MS or TOF
Protein purification of endogenous and recombinant proteins
cAMP-, and cytokine-assays, receptor binding studies, steady-state GTPase, GTP-binding of G-Proteins, ubiquitination assays
primary (neurons, glia, macrophages, mast cells) and cancer cells
migration-, apoptosis-, survival-, phocytosis- and proliferation-assays
Multi-Epitope-Ligand-Carthographie (MELC) Imaging, Calcium Imaging, FRET-based cAMP imaging, 3D reconstruction of immunhistochemical images, in vivo imaging
Animal models represent chronic human diseases, which currrently can not be treated satisfactory: Inflammatory, neurogenic and neuropathic (trauma-, tumor- and chemotherapy-induced) pain
1: Hohmann SW, Angioni C, Tunaru S, Lee S, Woolf CJ, Offermanns S, Geisslinger G, Scholich K, Sisignano M.
The G2A receptor (GPR132) contributes tooxaliplatin-induced mechanical pain hypersensitivity.
Sci Rep. 2017 27;7(1):446.
2: Zinn S, Sisignano M, Kern K, Pierre S, Tunaru S, Jordan H, Suo J, Treutlein EM, Angioni C, Ferreiros N, Leffler A, DeBruin N, Offermanns S, Geisslinger G, Scholich K.
The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons.
J Biol Chem. 2017 14;292(15):6123-6134.
3: Pierre S, Linke B, Suo J, Tarighi N, Del Turco D, Thomas D, Ferreiros N, Stegner D, Frölich S, Sisignano M, Meyer Dos Santos S, deBruin N, Nüsing RM, Deller T, Nieswandt B, Geisslinger G, Scholich K.
GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation.
J Invest Dermatol. 2017 137(3):686-695.
4: Sisignano M, Angioni C, Park CK, Meyer Dos Santos S, Jordan H, Kuzikov M, Liu D, Zinn S, Hohman SW, Schreiber Y, Zimmer B, Schmidt M, Lu R, Suo J, Zhang DD, Schäfer SM, Hofmann M, Yekkirala AS, de Bruin N, Parnham MJ, Woolf CJ, Ji RR, Scholich K, Geisslinger G.
Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain.
Proc Natl Acad Sci U S A. 2016 1;113(44):12544-12549.
5: Dörr A, Pierre S, Zhang DD, Henke M, Holland S, Scholich K.
MYCBP2 Is a Guanosine Exchange Factor for Ran Protein and Determines Its Localization in Neurons of Dorsal Root Ganglia.
J Biol Chem. 2015 16;290(42):25620-35.
6: Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain.
Nat Rev Neurol. 2014 10(12):694-707.
7: Suo J, Linke B, Meyer dos Santos S, Pierre S, Stegner D, Zhang DD, Denis CV, Geisslinger G, Nieswandt B, Scholich K. Neutrophils mediate edema formation but not mechanical allodynia during zymosan-induced inflammation.
J Leukoc Biol. 2014 96(1):133-42.
8: Schuh CD, Pierre S, Weigert A, Weichand B, Altenrath K, Schreiber Y, Ferreiros N, Zhang DD, Suo J, Treutlein EM, Henke M, Kunkel H, Grez M, Nüsing R, Brüne B, Geisslinger G, Scholich K.
Prostacyclin mediates neuropathic pain through interleukin 1β-expressing resident macrophages.
Pain. 2014 155(3):545-55
9: Sisignano M, Bennett DL, Geisslinger G, Scholich K. TRP-channels as key integrators of lipid pathways in nociceptive neurons.
Prog Lipid Res. 2014 53:93-107.
10: Schuh CD, Brenneis C, Zhang DD, Angioni C, Schreiber Y, Ferreiros-Bouzas N, Pierre S, Henke M, Linke B, Nüsing R, Scholich K, Geisslinger G.
Prostacyclin regulates spinal nociceptive processing through cyclic adenosine monophosphate-induced translocation of glutamate receptors.
Anesthesiology. 2014 120(2):447-58.
11: Degousee N, Simpson J, Fazel S, Scholich K, Angoulvant D, Angioni C, Schmidt H, Korotkova M, Stefanski E, Wang XH, Lindsay TF, Ofek E, Pierre S, Butany J, Jakobsson PJ, Keating A, Li RK, Nahrendorf M, Geisslinger G, Backx PH, Rubin BB.
Lack of microsomal prostaglandin E(2) synthase-1 in bone marrow-derived myeloid cells impairs left ventricular function and increases mortality after acute myocardial infarction.
Circulation. 2012 125(23):2904-13.
12: Sisignano M, Park CK, Angioni C, Zhang DD, von Hehn C, Cobos EJ, Ghasemlou N, Xu ZZ, Kumaran V, Lu R, Grant A, Fischer MJ, Schmidtko A, Reeh P, Ji RR, Woolf CJ, Geisslinger G, Scholich K, Brenneis C.
5,6-EET is released upon neuronal activity and induces mechanical pain hypersensitivity via TRPA1 on central afferent terminals.
J Neurosci. 2012 May 2;32(18):6364-72.
13: Holland S, Coste O, Zhang DD, Pierre SC, Geisslinger G, Scholich K.
The ubiquitin ligase MYCBP2 regulates transient receptor potential vanilloid receptor 1 (TRPV1) internalization through inhibition of p38 MAPK signaling.
J Biol Chem. 2011 286(5):3671-80.
14: Pierre S, Eschenhagen T, Geisslinger G, Scholich K. Capturing adenylyl cyclases as potential drug targets.
Nat Rev Drug Discov. 2009 8(4):321-35.
15: Linke B, Pierre S, Coste O, Angioni C, Becker W, Maier TJ, Steinhilber D, Wittpoth C, Geisslinger G, Scholich K. Toponomics analysis of drug-induced changes in arachidonic acid-dependent signaling pathways during spinal nociceptive processing.
J Proteome Res. 2009 8(10):4851-9.
16: Coste O, Brenneis C, Linke B, Pierre S, Maeurer C, Becker W, Schmidt H, Gao W, Geisslinger G, Scholich K. Sphingosine 1-phosphate modulates spinal nociceptive processing.
J Biol Chem. 2008 283(47):32442-51.
17: Pierre S, Maeurer C, Coste O, Becker W, Schmidtko A, Holland S, Wittpoth C, Geisslinger G, Scholich K. Toponomics analysis of functional interactions of the ubiquitin ligase PAM (Protein Associated with Myc) during spinal nociceptive
Mol Cell Proteomics. 2008 Dec;7(12):2475-85.
18: Scholich K, Geisslinger G.
Is mPGES-1 a promising target for pain therapy?
Trends Pharmacol Sci. 200627(8):399-401.
19: Pierre SC, Häusler J, Birod K, Geisslinger G, Scholich K.
PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate.
EMBO J. 2004 23(15):3031-40.
20: Scholich K, Mullenix JB, Wittpoth C, Poppleton HM, Pierre SC, Lindorfer MA, Garrison JC, Patel TB.
Facilitation of signal onset and termination by adenylyl
Science. 1999 283(5406):1328-31.