The Dermaut Lab is interested in understanding the genetic mechanisms leading to the loss of neurons and brain function during adulthood and aging. We focus on the discovery of novel genetic causes of rare neurological and neurodegenerative conditions by combining clinical, molecular genetic, single-cell and multi-omics approaches and use Drosophila melanogaster and cells for functional modeling of novel genes and variants. We hope that our contributions to the complex genetic landscape of rare neurological and neurodegenerative diseases will lead to better treatment options and a better quality of life of patients affected by these conditions.
- Alzheimer's disease (AD) is the most common neurodegenerative disorder. We have used Drosophila melanogaster to study the link between AD risk genes and the tau protein. We also discovered a role for tau in chromosomal instability.
- Amytrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) belong to a spectrum of severe neurodegenerative disorders in which the TDP-43 protein plays a central role. We study TDP-43 in Drosophila melanogaster and human cells and have discovered a novel role for TDP-43 in muscle degeneration.
- Mutations in RNF216 cause a form of ataxia, dementia and hypogonadism called Gordon Holmes syndrome, characterized by ubiquitin-positive neuronal inclusions. We discovered that this disorder can also present as a Huntington-like disorder and are studying the function of RNF216 and its role in inclusion formation.
Versluys L, Ervilha Pereira P, Schuermans N, De Paepe B, De Bleecker JL, Bogaert E, Dermaut B.
Front Neurosci. 2022 Feb 3;16:815765. doi: 10.3389/fnins.2022.815765. eCollection 2022.
Malmanche N, Dourlen P, Gistelinck M, Demiautte F, Link N, Dupont C, Vanden Broeck L, Werkmeister E, Amouyel P, Bongiovanni A, Bauderlique H, Moechars D, Royou A, Bellen HJ, Lafont F, Callaerts P, Lambert JC, Dermaut B.
Sci Rep. 2017 Jan 23;7:40764. doi: 10.1038/srep40764.
Santens P, Van Damme T, Steyaert W, Willaert A, Sablonnière B, De Paepe A, Coucke PJ, Dermaut B.
Neurology. 2015 Apr 28;84(17):1760-6. doi: 10.1212/WNL.0000000000001521. Epub 2015 Apr 3.
Vanden Broeck L, Callaerts P, Dermaut B.
Trends Mol Med. 2014 Feb;20(2):66-71. doi: 10.1016/j.molmed.2013.11.003. Epub 2013 Dec 16.
Vanden Broeck L, Naval-Sánchez M, Adachi Y, Diaper D, Dourlen P, Chapuis J, Kleinberger G, Gistelinck M, Van Broeckhoven C, Lambert JC, Hirth F, Aerts S, Callaerts P, Dermaut B.
Cell Rep. 2013 Jan 31;3(1):160-72. doi: 10.1016/j.celrep.2012.12.014. Epub 2013 Jan 17.
Rare neurological diseases
- Due to their extensive clinical and molecular heterogeneity, rare neurological disorders (RND) in adults are difficult to diagnose. Our lab is strongly involved in the discovery of genetic causes in challenging undiagnosed cases and participates in local (UD-PrOZA) and international rare disease initiatives (ERN-RND, Solve-RD).
- We have contributed to the discovery of several novel disease genes and created Drosophila models of novel neurological disease genes in collaboration with Solve-RD.
- RNF213 is a susceptibilty gene for Moyamoya disease (MMD), a rare cerebrovascular disorder with unknown etiology. In collaboration with Prof. dr. Francis Impens we are studying the role of immune-related responses such as infections to trigger MMD onset.
Schuermans N, Hemelsoet D, Terryn W, Steyaert S, Van Coster R, Coucke PJ, Steyaert W, Callewaert B, Bogaert E, Verloo P, Vanlander AV, Debackere E, Ghijsels J, LeBlanc P, Verdin H, Naesens L, Haerynck F, Callens S, Dermaut B, Poppe B; for UD-PrOZA.
Orphanet J Rare Dis. 2022 May 23;17(1):210. doi: 10.1186/s13023-022-02365-y.
Martina L, Asselman C, Thery F, Boucher K, Delhaye L, Maia TM, Dermaut B, Eyckerman S, Impens F.
Front Cell Infect Microbiol. 2021 Nov 3;11:735416. doi: 10.3389/fcimb.2021.735416. eCollection 2021.
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.
Thery F, Martina L, Asselman C, Zhang Y, Vessely M, Repo H, Sedeyn K, Moschonas GD, Bredow C, Teo QW, Zhang J, Leandro K, Eggermont D, De Sutter D, Boucher K, Hochepied T, Festjens N, Callewaert N, Saelens X, Dermaut B, Knobeloch KP, Beling A, Sanyal S, Radoshevich L, Eyckerman S, Impens F.
Nat Commun. 2021 Oct 1;12(1):5772. doi: 10.1038/s41467-021-26061-w.
Moyamoya disease emerging as an immune-related angiopathy.
AsselmanC, Hemelsoet D, Eggermon D, Dermaut B*, Impens F*
Trends in Molecular Medicine, September 14, 2022 - online ahead of print doi:https://doi.org/10.1016/j.molmed.2022.08.009 *shared last authorship