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Dr. Matthias Kirsch

PD Dr. Matthias Kirsch

Department of Anatomy and Cell Biology
University of Freiburg
Center for Neuroscience
Freiburg, Germany
Albertstraße 23
Tel.: +49-761-203-5381
Fax: +49-761-203-8433

matthias.kirsch@zfn.uni-freiburg.de
 

curriculum vitae

1978-85 Study of Biology at Univ. Ulm and Marburg


1987 DAAD-fellowship at the Imperial College London


1989 PhD; Project: The role of dopamine in the teleost retina


1989-1992 Postdoc at the Dept. Molecular and Cell Biology,Univ. California Berkeley/USA; Project: Polarized protein transport in vertebrate photoreceptors

since 1992 Dept. of Anatomy and Cell Biol., Neuroanatomy, Univ. Freiburg


2001 Habilitation in Anatomy

ongoing projects

Summary

Research in the lab is focused on the role of IL-6/gp130-associated cytokines in the nervous system. This family of cytokines has been shown to participate in a plethora of processes both during development and in the adult nervous system. In addition, members of this family have been found to be involved in regulating the response of glial cells following lesion in the adult nervous system.
For our studies to dissect the molecular pathways involved in mediating the activity of this family of cytokines we perform in vivo and in vitro studies using morphological, biochemical and molecular biological techniques.

gp130-associated cytokines and differentiation of retinal cells

gp130-associated cytokines e.g. ciliary neurotrophic factor (CNTF) has been shown be involved in regulating differentiation of retinal photoreceptors. We could show, that application of exogenous CNTF or the closely related family member LIF (leukemia inhibitory factor) blocks photoreceptor differentiation in dissociated retinal cell cultures, retinal slice preparations and in whole retina cultures. In the presence of these factors cells fail to express photoreceptor proteins and instead express marker proteins for retinal bipolar cells. However, with the use of organotypic slice cultures, we could show, that these cells continue to reside in the photoreceptor layer and retain their photoreceptor morphology. These results suggest that only particular aspects of photoreceptor/bipolar cell differentiation are regulated by these cytokines.

Regulation of postlesional activation of astrocytes by gp130-associated cytokines

Following lesions in the central nervous system (CNS) glial cells (astrocytes and microglial cells) are activated. Glial activation serves to remove cellular debris, provide trophic support to damaged cells and to restore the compromised blood-brain-barrier. However, besides these beneficial effects, activated glial cells, in particular astrocytes, are also thought to prevent successful regeneration in the CNS by forming an impenetrable glial scar together with connective tissue cells. The molecular signals regulating the activational state of astrocytes are largely unknown. It has been suggested that gp130-associated cytokines play a central role in glial activation. In support of this, we could show that activated astrocytes upregulate expression of various components of the signal transduction machinery of this cytokine family (e.g. ligands, receptor components, target genes) and phosphorylated STAT3, one of the main signal-transduction intermediates of the JAK/STAT-pathway. Astroglial activation is abrogated in mouse mutants which lack LIF or are incapable to activate the JAK/STAT-pathway. These results underscore the importance of this cytokine family in astroglial activation. Blocking the activity of the JAK/STAT-pathway may offer a means to reduce glial scar formation thereby enhancing regeneration in the lesioned CNS.

Neurogenesis in the adult nervous system

In the adult nervous system new neurons continue to be produced in two neurogenic regions: the lateral ventricle subventricular zone (SVZ) and the subgranular zone of the dentate gyrus. This finding shows that a pool of multipotent neural stem cells is present in the adult CNS. Understanding how proliferation and differentiation of adult neural stem cells are regulated on a molecular level is a central issue of our current research, as it offers the opportunity to guide these cells towards replacing neurons lost following traumatic brain injury or neurodegenerative disease. gp130-associated cytokines have been identified to be among the extracellular signals which regulate proliferation and cell fate decisions of neural stem cells. In in vivo experiments using mouse mutants and in in vitro studies with organotypic hippocampal slice cultures, we try to elucidate how these cytokines exert their influence on neural stem cells.

 

Development of neuroprotective neurosteroid analogs

Our observation that immature neural stem cells are exquisitely sensitive to the toxic effects of ß-amyloid, the accumulation of which is one of the causes leading to Alzheimer's disease, directed our interest towards strategies designed to ameliorate its deleterious effects. In a collaborative approach with scientists from Strasbourg and Basel we identified lead compound that show great potential to be developed into therapeutic tools.

 

 

selected publications

Karout M., Miesch M., Geoffroy P., Kraft S., Hofmann H.-D., Mensah-Nyagan A .G. and Kirsch M. (2016) Novel analogs of allopregnanolone show improved efficiency and specificity in neuroprotection and stimulation of proliferation. J Neurochem. Jun 3.

Janz P., Savanthrapadian S., Häussler U., Kilias A., Nestel S., Kretz O., Kirsch M., Bartos M., Egert U., and Haas C. A. (2016) Synaptic Remodeling of Entorhinal Input Contributes to an Aberrant Hippocampal Network in Temporal Lobe Epilepsy. Cereb Cortex. Apr 12

Bohrer C., Pfurr S., Mammadzada K., Schildge S., Plappert L., Hils M., Pous L., Rauch K. S., Dumit V. I., Pfeifer D., Dengjel J., Kirsch M., Schachtrup K.and Schachtrup C. (2015) The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes. EMBO J. 34: 2804-2819

Bechstein M., Häussler U., Neef M., Hofmann H.-D., Kirsch M. and Haas CA. (2012) CNTF-mediated preactivation of astrocytes attenuates neuronal damage and epileptiform activity in experimental epilepsy. Exp Neurol. 236:141-50

Hofmann H.-D. and Kirsch M. (2012) JAK2-STAT3 signaling: A novel function and a novel mechanism. JAKSTAT 1:191-3

Kirsch M., Trautmann N., Ernst M. and Hofmann H.-D. (2010) Involvement of gp130-associated cytokine signaling in Müller cell activation following optic nerve lesion. Glia 68:768-779

Kirsch M., Campos Friz M., Vougioukas V. I. and Hofmann H.-D. (2009) Wallerian degeneration and axonal regeneration after sciatic nerve crush are altered in ICAM-1-deficient mice. Cell Tiss. Res. 338:19-28

Müller S., Sasidharan B. P., Schwegler, H., Hofmann H.-D. and Kirsch M. (2009) Neurogenesis in the dentate gyrus depends on CNTF and STAT3 signaling. Stem Cells 27:431-441

Leibinger M., Müller A., Andreadaki A., Hauk T. G., Kirsch M. and Fischer D. (2009) Neuroprotective and Axon Growth-Promoting Effects following Inflammatory Stimulation on Mature Retinal Ganglion Cells in Mice Depend on Ciliary Neurotrophic Factor and Leukemia Inhibitory Factor. J. Neurosci. 29:14334-14341

Weitere Publikationen: siehe auch in der Forschungsdatenbank der Universität Freiburg

ORCID iD: 0000-0002-2090-8556
http://freiburg.wizper.org/Arbeitsgruppe/kirsch

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