Prof. Dr. med. Thomas Misgeld

Brief research description:
We study axon changes in the healthy and in the sick nervous system of living animals. Axons are the long neuronal processes that form synapses and thus interconnect different parts of the nervous system. Obviously, to properly establish wiring in the brain, myriads of axons have to find their targets, or otherwise, axons that connect incorrectly need to be removed. We are interested in the latter process – not only because such axon dismantling contributes fundamentally to brain development and to the adaptation of our neural circuits to the environment, but also because axons are highly susceptible to pathology. Many common neurological diseases are characterized by early loss of axonal connections – including motor neuron disease, spinal cord injury and multiple sclerosis, all of which we study. By better understanding axon dismantling in development and disease we hope to gain insight into what causes axons to disintegrate under pathological conditions. Our investigations addressing the questions raised above motivate studies into the role of neuro-glial interactions that maintain and dismantle axons, into the principles of axonal transport and of organelle turnover, especially of mitochondria, and of the role that the axonal cytoskeleton plays in giving axons shape and ensuring organelle supply. To address these questions, we use in vivo imaging approaches in zebrafish and mice.

Key words: neurodegeneration, synapse development, multiple sclerosis, in vivo imaging, spinal cord

Current GSN students: Adrian Marti Pastor, Ioanna Emmanouilidis, Katharina Eichenseer, Lorena Olifiers, Shahrzad Askari

Graduated GSN students: Dr. Pui Shee Lee, Dr. Eleni Petridou, Dr. Antoneta Gavoci, Dr. Selin Kenet, Dr. Caroline Fecher

Selected publications: 

Fecher C, Trovò L, Müller SA, Snaidero N, Wettmarshausen J, Heink S, Ortiz O, Wagner I, Kühn R, Hartmann J, Karl RM, Konnerth A, Korn T, Wurst W, Merkler D, Lichtenthaler SF, Perocchi F, Misgeld T Cell type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat Neurosci 2019 Oct;22(10):1731-1742. doi: 10.1038/s41593-019-0479-z. Epub 2019 Sep 9.

Brill MS, Kleele T, Ruschkies L, Wang M, Marahori NA, Reuter MS, Hausrat TJ, Weigand E, Fisher M, Ahles A, Engelhardt S, Bishop DL, Kneussel M, Misgeld T. Branch-Specific Microtubule Destabilization Mediates Axon Branch Loss during Neuromuscular Synapse Elimination. Neuron. 2016 Nov 23; 92:845-856. doi: 10.1016/j.neuron.2016.09.049

Breckwoldt M.O., Pfister F., Bradley P.M., Marinkovic P., Williams P.W., Brill M.S., Plomer B., Schmalz A., St Clair D.K., Naumann R., Griesbeck O., Schwarzländer M., Godinho L., Bareyre F.M., Dick T.P., Kerschensteiner M. & Misgeld T. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Nature Medicine. 2014 Apr 27; 20:555-560. doi: 10.1038/nm.3520

Nikić I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Brück W, Bishop D, Misgeld T*, Kerschensteiner M. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2011 Apr 01; 17:495-9. doi: 10.1038/nm.2324 (*equal senior author)

Kerschensteiner M, Schwab ME, Lichtman JW, Misgeld T. In vivo imaging of axonal degeneration and regeneration in the injured spinal cord. Nat Med. 2005 May 01; 11:572-7.