Chrast Laboratory

Senior researcher

Roman Chrast

Telefon: 08-524 878 25
E-post: roman.chrast@ki.se

Research focus

We are interested in the biology and disease of myelinating glial cells. Both oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system produce myelin necessary for the insulation of axons allowing for fast propagation of action potentials. In addition to their capacity to myelinate, oligodendrocytes and Schwann cells also play a critical role in axonal support.  Deregulation of these glial functions lead to detrimental central and peripheral deficiencies, mainly characterized by demyelination and/or axonal degeneration. We are using two parallel and complementary strategies to understand and potentially prevent disease-induced changes in myelinating glia:

1. The first approach is based on genetics. We work in close collaboration with clinicians to identify genes that are mutated in various forms of diseases affecting myelinating glia. Once the mutated gene is identified, we work on modeling of the disease using both in vitro and in vivo approaches in order to uncover underlying pathophysiological mechanisms.

2. Our second strategy is based on detailed characterization of the key mechanisms involved in the biology of glial cells with a particular accent on their capacity to produce myelin and to support the underlying axon. We anticipate that the insights gained through this characterization will be important not only for the understanding of biology of neurons and glia, but may also lead to discovery of new therapeutical targets that could be explored in a larger context of neurodegenerative diseases. 

Nile red (Nr) staining of myelin of teased fibers prepared from sciatic nerves isolated from wild-type (Sh3tc2+/+) and Sh3tc2-/- mice (model of CMT4C neuropathy) reveal presence of widened nodes of Ranvier (arrowheads) in affected animals (Arnaud et al., 2009).

Selected publications

Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.
Bernard-Marissal N, Médard J, Azzedine H, Chrast R
Brain 2015 Apr;138(Pt 4):875-90

Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.
Domènech-Estévez E, Baloui H, Repond C, Rosafio K, Médard J, Tricaud N, et al
J. Neurosci. 2015 Mar;35(10):4151-6

A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.
Zenker J, Stettner M, Ruskamo S, Domènech-Estévez E, Baloui H, Médard J, et al
Glia 2014 Sep;62(9):1502-12

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.
Azzedine H, Zavadakova P, Planté-Bordeneuve V, Vaz Pato M, Pinto N, Bartesaghi L, et al
Hum. Mol. Genet. 2013 Oct;22(20):4224-32

Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.
Zenker J, Poirot O, de Preux Charles A, Arnaud E, Médard J, Lacroix C, et al
J. Neurosci. 2012 May;32(22):7493-8

Group members

Hasna Baloui - Senior postdoc

Luca Bartesaghi - Postdoc

Filipa Bouçanova da Silva - PhD student

Roman Chrast - Senior researcher

Enric Domenech-Estevez - Senior postdoc

Jean-Jacques Medard - Laboratory engineer

Olivia Miossec - student