Ludo Van Den Bosch Lab

Research focus

​The group of Ludo Van Den Bosch focuses on the mechanisms of acute and chronic axonal and neuronal degeneration and regeneration, aiming to contribute to the development of new therapeutic strategies for neurodegenerative disorders. This group intensively studies motor neuron diseases (amyotrophic lateral sclerosis (ALS) and hereditary motor neuropathies), frontotemporal dementia (FTD) and stroke.

Both familial (autosomal dominant) and sporadic forms of ALS are known. Mutations in several genes are the cause familial ALS: SOD1, FUS and TDP-43 mutations being the most important ones, in addition to the recently discovered hexanucleotide repeats in the non-coding region of the C9orf72 gene.

The group investigates the role of excitotoxicity, phase transitions and stress granule formation, the contribution of non-neuronal cells and the therapeutic potential of nanobodies. Furthermore, the genetic contribution to the pathogenesis of ALS is a main topic of study. This group has developed a zebrafish and a Drosophila model to perform screenings for disease-modifying genetic factors. EphA4, histone deacetylase 6 (HDAC6) and factors involved in nucleocytoplasmic transport were discovered as important modifiers. Recently, the lab has established iPSC-derived motor neuron models to further investigate the disease mechanisms linked to these modifiers. In the future, these cells will also be used to investigate potential therapeutic strategies for ALS.

Axonal degeneration of the motor axon is the main characteristic of Charcot-Marie-Tooth disease and of distal hereditary motor neuropathy (distal HMN). The group of Ludo Van Den Bosch also focuses on the pathogenic mechanisms underlying these diseases, with a particular focus on HSPB1 and GARS. The research concentrates on the involvement of cytoskeletal modifications (and in particular alpha-tubulin acetylation) in the pathogenesis of these peripheral neuropathies. Also for this disease, the lab uses iPSC-derived motor neuron model to investigate disease mechanisms. 

Both clinically and pathologically, there is a clear link between ALS and FTD. Familial forms of FTD can be caused by mutations in the progranulin gene and by hexanucleotide repeats in the C9orf72 gene. Moreover, TDP-43 aggregates are a hallmark of FTD. Therefore, the molecular relationship between these two disorders is studied by investigating the biology of progranulin, TDP-43 and C9orf72.
                 
Finally, to elucidate the mechanisms underlying axonal regeneration, paradigms of acute neurodegeneration relevant to stroke and recovery from stroke are also a topic of study in this laboratory.      
       
This research is being conducted by using both in vitro (glial and motor neuron cultures) and in vivo models (spontaneous, induced and transgenic models for acute and chronic neurodegeneration). Genetic and clinical studies are being performed in close relationship with the Department of Neurology at the University Hospitals Leuven.

Interested in the molecular mechanisms of ALS?
Watch this beautiful animation Nature Reviews Disease Primers made based on input of the group of Ludo Van Den Bosch and Wim Robberecht (VIB-KU Leuven).
nature.com/animations/ALS17

Poster: Molecular mechanisms of amyotrophic lateral sclerosis
Nat Rev Neurosci  2016

Publications

Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule DynamicsBoeynaems S Bogaert E Kovacs D Konijnenberg A Timmerman E Volkov O Guha Roy M De Decker M Jaspers T Ryan V Janke A Baatsen P Vercruysse T Kolaitis R Daelemans D Taylor J Kedersha N Anderson P Impens F Sobott F Schymkowitz J Rousseau F Fawzi N Robberecht W Van Damme P Tompa P* Van Den Bosch L*MOLECULAR CELL, 65, 1044-1055 e5, 2017* These authors contributed equally
HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patientsGuo W Naujock M Fumagalli L Vandoorne T Baatsen P Boon R Ordovas L Patel A Welters M Vanwelden T Geens N Tricot T Benoy V Steyaert J Lefebvre-Omar C Boesmans W Jarpe M Sterneckert J Wegner F Petri S Bohl D Vanden Berghe P Robberecht W Van Damme P Verfaillie C* Van Den Bosch L*Nature Communications, 8, 861, 2017* These authors contributed equally
Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in vivoBeel S, Moisse M, Damme M, De Muynck L, Robberecht W, Van Den Bosch L, Saftig P, Van Damme PHUMAN MOLECULAR GENETICS, 26, 2850-2863, 2017
Inside out: the role of nucleocytoplasmic transport in ALS and FTLDBoeynaems S, Bogaert E, Van Damme P, Van Den Bosch LACTA NEUROPATHOLOGICA, 132, 159-73, 2016
HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth diseasevan Outryve d'Ydewalle C, Krishnan J, Chiheb D, Van Damme P, Irobi J, Kozikowski A, Vanden Berghe P, Timmerman V, Robberecht W, Van Den Bosch LNATURE MEDICINE, 17, 968-74, 2011

Job openings

News

Resolving traffic jams in human ALS motor neurons

17/10/2017 - ​A team of researchers at VIB and KU Leuven used stem cell technology to generate motor neurons from ALS patients carrying mutations in FUS.

Winning at basic science: collaboration is critical

30/06/2017 - A research team with Ludo Van Den Bosch at its helm has identified a new process that leads to the neurodegenerative brain diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

A diagnostic test for ALS

19/06/2017 - Researchers at VIB, KU Leuven, and UZ Leuven, in collaboration with researchers at the University of Jena, have demonstrated that measuring neurofilaments provides reliable confirmation of an ALS diagnosis.

A new role for progranulin, as a cathepsin D chaperone

08/05/2017 - ​In a recent study in Human Molecular Genetics, researchers from VIB and KU Leuven led by prof. Philip Van Damme, reveal a novel function for progranulin in lysosomes: it acts as chaperone of the lysosomal protease cathepsin D.

New toxic pathway identified for protein aggregates in neurodegenerative disease

17/03/2017 - Led by professor Ludo Van Den Bosch (VIB-KU Leuven), scientists from Belgium, the UK and the US have identified new processes that form protein “clumps” that are characteristic of ALS and frontotemporal lobar degeneration (FTLD).

Onward to new therapies for neurodegenerative diseases ALS and FTD

20/08/2016 - ALS & FTD are fatal, adult-onset neurodegenerative disorders. The group of Ludo Van Den Bosch and Wim Robberecht (VIB/KU Leuven) has discovered profound new insights into the causes of these diseases that will drive future research

Promising new insights into ALS

14/07/2016 - Research into amyotrophic lateral sclerosis (ALS) conducted by VIB-KU Leuven has led to interesting and unexpected conclusions. This research was conducted in the VIB Laboratory of Neurobiology, led by professors Ludo Van Den Bosch and Wim Robberecht.

Important role of nucleocytoplasmic transport in amyotrophic lateral sclerosis and frontotemporal dementia

12/02/2016 - Moreover, these insights have a solid basis, since they come from 4 different scientific angles. It is an important next step in our understanding of these terrible diseases.”

Stem cell research offers new insights into how dementia develops

05/01/2015 - ​Researchers at KU Leuven and the Vlaams Instituut voor Biotechnologie (VIB) have succeeded in correcting a genetic mutation thought to cause frontotemporal dementia.

Zebra fish point the way towards new therapies for amyotrophic lateral sclerosis

27/08/2012 - Leuven scientists (VIB/KU Leuven) are using zebrafish as a model in their search for genes that play a role in the mechanism of amyotrophic lateral sclerosis (ALS).

Mice point to a therapy for Charcot-Marie-Tooth disease

02/08/2011 - VIB researchers have developed a mouse model for Charcot-Marie-Tooth (CMT) neuropathy, a hereditary disease of the peripheral nervous system. They also found a potential therapy for this incurable disease.

Ludo Van Den Bosch

Ludo Van Den Bosch

Research area(s)

Model organism(s)

Bio

PhD: KU Leuven, Leuven, Belgium, 1990
Associate Prof.: KU Leuven, Leuven, Belgium, 2002-13
Professor KU Leuven since 2013
VIB Group leader since October 2013

Contact Info

VIB-KU Leuven Center for Brain & Disease ResearchO&N 4, 6e verdCampus GasthuisbergHerestraat 49, bus 602 3000 LEUVENRoute description