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Research Group Michaela Kress

Group/personal information:

Group title: Physiology and pathophysiology of the nociceptive system
Group leader: Michaela Kress, Univ-Prof. Dr. med.
Location: Schoepfstr. 41, 6020 Innsbruck
E-mail: michaela.kress@i-med.ac.at
Phone: +43 (0) 512 9003 70800, -01, -02
ORCID: https://orcid.org/0000-0002-8921-7470

Scientific interests:

Regulators of nociceptor development and function for pain and disturbed brain-body-brain loops

Current research topics:

• Modelling human nociception
• Non-coding RNAs in nociceptor development, neuropathic pain and neuronal regeneration
• Pro-inflammatory cytokines in the development and chronification of neuropathic pain
• Role of sensory neurons in the gut brain axis

Main methodologies:

• iPSC derived human model systems
• Electrophysiology (Multi electrode array, extracellular recordings, single cell patch-clamp)
• Sensory-motor phenotyping
• Neuropathic pain models
• Primary neuron cultures
• Expression analysis (RT-qPCR, in situ hybridization, Western blot, immunocytochemistry, immunohistochemistry, ELISA, etc)
• Microfluorimetric Ca²⁺ measurements
• Computational neuroscience
• Two-Photon-Mikroscopy (Biooptics Core Facility - contact: kai.kummer@i-med.ac.at)
• Live imaging

Current lab members:

Postdocs:
Nadiia Rykalo
Buket Ucar
n.n.

PhD students:
Lydia Riehl
David Zimmermann

Technical support:
Kathrin Braun
Federica Vercelli
Valentia Handle
n.n.

Collaborators:

Zameel Cader (Uni Oxford, UK)
Paul Heppenstall (nn)
Stefan Lichtenthaler (LMU München, Germany)
Stefan Rose-John (Christian-Albrechts-Universität zu Kiel, Germany)
Susanne K Sauer (Friedrich-Alexander-Universität Erlangen, Germany)
Hermona Soreq (Hebrew University of Jerusalem, Israel)

Full publication list:

https://orcid.org/0000-0002-8921-7470/print

Funding:

POCDMiBIOME - Fonds zur Förderung Wissenschaftlicher Forschung (FWF):

Globally, more than 320 million people have surgery per year and incidence of postoperative cogntiive dysfunction (POCD) at 3 months posts-op is still 12 % affecting >30 million people. Despite this considerable socioeconomic burden POCD pathogenesis remains largely unknown. POCDMiBiOME explores the contribution of Nav1.8 expressing nociceptive neurons and gp130 for surgery induced cognitive deficits. Whereas POCD is traditionally considered a direct consequence of surgical intervention or anesthesia, POCDMiBiOME shifts the focus from a brain-restricted to a body-brain-body approach in the novel research area of gut-brain-communication.

Riehl L, Fürst J, Kress M, Rykalo N. The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders.Front Neurosci. 2024 Jan 5;17:1302957. doi: 10.3389/fnins.2023.1302957.

PainMSK - FWF

Tissue injuries of various origins induce inflammation and this in turn causes inflammatory pain which is characterized by hypersensitivity to heat and mechanical stimuli. Pain of inflammatory origin affects about 50 percent of people at some point during their life. The nuclear enzymes mitogen and stress-activated kinase (MSK) 1 and MSK2 are important for heat hypersensitivity of inflamed tissue. In an international collaboration with Prof. Dr. I. Nagy at Debrecen University (Hungary) and Imperial College London (UK), an integrated and multidisciplinary approach will be used to construct the MSK1-dependent molecular networks and identify hub molecules responsible for the development of inflammatory heat hypersensitivity.

NIPPS (FWF) - completed

The NIPPS project has elucidated the role of IL-6/gp130 in nociceptors in the generation of neuropathic pain and hyperalgesia, profiled IL-6/gp130 dependent neuroimmune interactions in the mouse SNI model and explored the involvement of microRNAs in neuroimmune interactions towards improved resolution of maladaptive pain.

Kalpachidou T, Riehl L, Schöpf CL, Ucar B, Kress M. Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain. Pain. 2022 Nov 1;163(Suppl 1):S79-S98. doi: 10.1097/j.pain.0000000000002737.

Kalpachidou T, Malsch P, Qi Y, Mair N, Geley S, Quarta S, Kummer KK, Kress M. Genetic and functional evidence for gp130/IL6ST-induced transient receptor potential ankyrin 1 upregulation in uninjured but not injured neurons in a mouse model of neuropathic pain. Pain. 2022 Mar 1;163(3):579-589. doi: 10.1097/j.pain.0000000000002402.

Kummer KK, Zeidler M, Kalpachidou T, Kress M. Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine. 2021 Aug;144:155582. doi: 10.1016/j.cyto.2021.155582. Epub 2021 May 29.

Kalpachidou T, Kummer KK, Kress M. Non-coding RNAs in neuropathic pain. Neuronal Signal. 2020 Apr;4(1):NS20190099. doi: 10.1042/NS20190099. Epub 2020 Apr 23.

Ebbinghaus M, Segond von Banchet G, Massier J, Gajda M, Bräuer R, Kress M, Schaible HG. Interleukin-6-dependent influence of nociceptive sensory neurons on antigen-induced arthritis. Arthritis Res Ther. 2015 Nov 21;17:334. doi: 10.1186/s13075-015-0858-0.

CeRNAPsych (FFG) - completed

The ceRNAPsych pilot project aimed to advance personalized medicine by identifying a new subset of mental disease-relevant genes and genomic changes that were so far neglected as being ‘functionally irrelevant’ and by shedding new understanding on the pathogenesis of psychiatric disorders such as schizophrenia, autism and mood disorders. Novel regulatory mechanisms were studied such as miRNA regulation and competing endogenous RNA that until recently were either little studied or completely unknown in the context of brain functioning. Improved RNA sequencing tools were developed by our industry partner Lexogen GmbH (Vienna)

TOBEaTPAIN (Beneficiary - MSCA-ITN, European Commission, GA764860) - completed

TOBeATPAIN suggested that neuroinflammation represents an underlying mechanism of pathological pain states encompassing those with a PNS or CNS origin. The focus of this ITN was on the mechanisms by which non-neuronal cells impact on neuronal activity in order to identify innovative non-neuronal targets for the treatment of pathological pain in peripheral macrophages or CNS microglia/astrocytes.
Two PhD students were trained on independent projects and one student hosted for a secondment.

Choconta JL, Labi V, Dumbraveanu C, Kalpachidou T, Kummer KK, Kress M. Age-related neuroimmune signatures in dorsal root ganglia of a Fabry disease mouse model. Immun Ageing. 2023 May 12;20(1):22. doi: 10.1186/s12979-023-00346-8.

Dumbraveanu C, Strommer K, Wonnemann M, Choconta JL, Neumann A, Kress M, Kalpachidou T, Kummer KK. Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment. Pharmaceutics. 2023 Mar 6;15(3):853. doi: 10.3390/pharmaceutics15030853.

Gimeno-Ferrer F, Eitner A, Bauer R, Lehmenkühler A, Edenhofer ML, Kress M, Schaible HG, Richter F From spreading depolarization to epilepsy with neuroinflammation: The role of CGRP in cortex.. Exp Neurol. 2022 Oct;356:114152. doi: 10.1016/j.expneurol.2022.114152.

ncRNAPAIN (Coordinator - RIA, European Commission, GA602133) - completed

Neuro-immune alterations in the peripheral and central nervous system play a critical role in the pathophysiology of neuropathic pain. Non-coding RNAs (ncRNAs) incl. microRNAs (miRs) regulate both immune and neuronal processes.as master switches for circuitries and processes modulating nociception, endogenous analgesia as well as cognitive, emotional and behavioural components of pain. The ncRNAPain consortium has assessed ncRNA regulation in the pain pathway to gain novel mechanistic insight into neuropathic pain syndromes.

Zeidler M, Tavares-Ferreira D, Brougher J, Price TJ, Kress M. NOCICEPTRA2.0 - A comprehensive ncRNA atlas of human native and iPSC-derived sensory neurons.
iScience. 2023 Nov 23;26(12):108525. doi: 10.1016/j.isci.2023.108525.

Ranches G, Zeidler M, Kessler R, Hoelzl M, Hess MW, Vosper J, Perco P, Schramek H, Kummer KK, Kress M, Krogsdam A, Rudnicki M, Mayer G, Huettenhofer A. Exosomal mitochondrial tRNAs and miRNAs as potential predictors of inflammation in renal proximal tubular epithelial cells. Mol Ther Nucleic Acids. 2022 May 4;28:794-813. doi: 10.1016/j.omtn.2022.04.035. eCollection 2022 Jun 14.PMID: 35664695

Towards Zeidler M, Kummer KK, Kress M. bridging the translational gap by improved modeling of human nociception in health and disease. Pflugers Arch. 2022 Sep;474(9):965-978. doi: 10.1007/s00424-022-02707-6. Epub 2022 Jun 3.PMID: 35655042

Zeidler M, Kummer KK, Schöpf CL, Kalpachidou T, Kern G, Cader MZ, Kress M. NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC-Derived Nociceptor Maturation. Adv Sci (Weinh). 2021 Nov;8(21):e2102354. doi: 10.1002/advs.202102354. Epub 2021 Sep 5. PMID: 34486248

Lozano F, Mehling K, Forer L, Kress M, Üçeyler N, Sommer C, Dimova V, Birklein F, Rittner HL. Complex regional pain syndrome: role of contralateral sensitisation. Dietz C, Reinhold AK, Escolano- Br J Anaesth. 2021 Jul;127(1):e1-e3. doi: 10.1016/j.bja.2021.03.018. Epub 2021 May 1. PMID: 33941363

Kalpachidou T, Kummer KK, Kress M. Non-coding RNAs in neuropathic pain. Neuronal Signal. 2020 Apr;4(1):NS20190099. doi: 10.1042/NS20190099. Epub 2020 Apr 23. PMID: 32587755

Zeidler M, Hüttenhofer A, Kress M, Kummer KK. Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways-A Cross-Species Analysis. Cells. 2020 Jan 17;9(1):232. doi: 10.3390/cells9010232. PMID: 31963421

Kalpachidou T, Kummer KK, Mitrić M, Kress M. Tissue Specific Reference Genes for MicroRNA Expression Analysis in a Mouse Model of Peripheral Nerve Injury. Front Mol Neurosci. 2019 Nov 22;12:283. doi: 10.3389/fnmol.2019.00283. eCollection 2019. PMID: 31824261

Dietz C, Müller M, Reinhold AK, Karch L, Schwab B, Forer L, Vlckova E, Brede EM, Jakubietz R, Üçeyler N, Meffert R, Bednarik J, Kress M, Sommer C, Dimova V, Birklein F, Rittner HL. What is normal trauma healing and what is complex regional pain syndrome I? An analysis of clinical and experimental biomarkers. Pain. 2019 Oct;160(10):2278-2289.doi:10.1097/j.pain.0000000000001617. PMID: 31095096

Kress M, Hüttenhofer A, Landry M, Kuner R, Favereaux A, Greenberg D, Bednarik J, Heppenstall P, Kronenberg F, Malcangio M, Rittner H, Uçeyler N, Trajanoski Z, Mouritzen P, Birklein F, Sommer C, Soreq H. microRNAs in nociceptive circuits as predictors of future clinical applications. Front Mol Neurosci. 2013 Oct 17;6:33. doi: 10.3389/fnmol.2013.00033. PMID: 24151455

Selected other publications:

Sartori SB, Keil TMV, Kummer KK, Murphy CP, Gunduz-Cinar O, Kress M, Ebner K, Holmes A, Singewald N. Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex. Transl Psychiatry. 2024 Jan 8;14(1):11. doi: 10.1038/s41398-023-02708-8.

Kokotović T, Lenartowicz EM, Langeslag M, Ciotu CI, Fell CW, Scaramuzza A, Fischer MJM, Kress M, Penninger JM, Nagy V. Transcription factor mesenchyme homeobox protein 2 (MEOX2) modulates nociceptor function. FEBS J. 2022 Jun;289(12):3457-3476. doi: 10.1111/febs.16347. Epub 2022 Feb 16.PMID: 35029322

May MA, Kummer KK, Edenhofer ML, Choconta JL, Kress M, Ritsch-Marte M, Jesacher A. Simultaneous scattering compensation at multiple points in multi-photon microscopy.

Biomed Opt Express. 2021 Nov 9;12(12):7377-7387. doi: 10.1364/BOE.441604. eCollection 2021 Dec 1.PMID: 35003840

Kokotović T, Langeslag M, Lenartowicz EM, Manion J, Fell CW, Alehabib E, Tafakhori A, Darvish H, Bellefroid EJ, Neely GG, Kress M, Penninger JM, Nagy V. PRDM12 Is Transcriptionally Active and Required for Nociceptor Function Throughout Life. Front Mol Neurosci. 2021 Sep 27;14:720973. doi: 10.3389/fnmol.2021.720973. eCollection 2021.PMID: 34646120 

May MA, Barré N, Kummer KK, Kress M, Ritsch-Marte M, Jesacher A. Fast holographic scattering compensation for deep tissue biological imaging. Nat Commun. 2021 Jul 15;12(1):4340. doi: 10.1038/s41467-021-24666-9.PMID: 34267207

May MA, Bawart M, Langeslag M, Bernet S, Kress M, Ritsch-Marte M, Jesacher A. High-NA two-photon single cell imaging with remote focusing using a diffractive tunable lens. Biomed Opt Express. 2020 Nov 16;11(12):7183-7191. doi: 10.1364/BOE.405863. eCollection 2020 Dec 1.PMID: 33408989

Moschetti G, Kalpachidou T, Amodeo G, Lattanzi R, Sacerdote P, Kress M, Franchi S. Prokineticin Receptor Inhibition With PC1 Protects Mouse Primary Sensory Neurons From Neurotoxic Effects of Chemotherapeutic Drugs in vitro. Front Immunol. 2020 Sep 24;11:2119. doi: 10.3389/fimmu.2020.02119. eCollection 2020.PMID: 33072073

Langeslag M, Kress M. The ceramide-S1P pathway as a druggable target to alleviate peripheral neuropathic pain. Expert Opin Ther Targets. 2020 Sep;24(9):869-884. doi: 10.1080/14728222.2020.1787989. Epub 2020 Jul 9.PMID: 32589067

Schoepf CL, Zeidler M, Spiecker L, Kern G, Lechner J, Kummer KK, Kress M. Selected Ionotropic Receptors and Voltage-Gated Ion Channels: More Functional Competence for Human Induced Pluripotent Stem Cell (iPSC)-Derived Nociceptors. Brain Sci. 2020 Jun 3;10(6):344. doi: 10.3390/brainsci10060344.PMID: 32503260

Kummer KK, Mitrić M, Kalpachidou T, Kress M. The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain. Int J Mol Sci. 2020 May 13;21(10):3440. doi: 10.3390/ijms21103440.PMID: 32414089

Wilke BU, Kummer KK, Leitner MG, Kress M. Chloride - The Underrated Ion in Nociceptors. Front Neurosci. 2020 Apr 8;14:287. doi: 10.3389/fnins.2020.00287. eCollection 2020.PMID: 32322187

Mitrić M, Seewald A, Moschetti G, Sacerdote P, Ferraguti F, Kummer KK, Kress M. Layer- and subregion-specific electrophysiological and morphological changes of the medial prefrontal cortex in a mouse model of neuropathic pain. Sci Rep. 2019 Jul 1;9(1):9479. doi: 10.1038/s41598-019-45677-z.PMID: 31263213

Kalpachidou T, Spiecker L, Kress M, Quarta S. Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons. Cells. 2019 Jun 15;8(6):591. doi: 10.3390/cells8060591.PMID: 31208035

Quarta S, Mitrić M, Kalpachidou T, Mair N, Schiefermeier-Mach N, Andratsch M, Qi Y, Langeslag M, Malsch P, Rose-John S, Kress M. Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

FASEB J. 2019 Mar;33(3):4418-4431. doi: 10.1096/fj.201801901R. Epub 2018 Dec 26.PMID: 30586315

Alumni:

Dr. Manfred Andratsch
Dr. Christina Constantin
Cristiana Dumbraveanu
Jeiny Luna Choconta
Philipp Malsch (PhD)
Miodrag Mitric (PhD)
Serena Quarta (PhD)
Yanmei Qi (PhD)
Nadja Jaubert (Prof. Dr., geb. Scherbakov)
Natalia Schiefermeier (Prof. Dr.)
Daniela Weth (PhD)
Maximilian Zeidler (PhD)