Neurodegenerative diseases
Amyotrophic Lateral Sclerosis, Frontotemporal Dementia & Spinocerebellar Ataxia
With the aging of our populations, neurodegenerative diseases are increasing in their prevalence, posing an enormous societal burden. All of these disorders remain currently without a cure. My work focuses on understanding the molecular underpinnings of a group of closely-related diseases. In ALS, motor neurons in the motor cortex, brainstem, and spinal cord degenerate, resulting in rapidly progressive muscle weakness, paralysis, and death. While in FTD, degeneration affects frontal and temporal regions, resulting in most commonly behavioral changes and aphasia. SCA is characterized by problems with coordination, balance and speech, and stems from the demise of specific cerebellar neuron populations.
Even though these diseases may be sporadic in origin or caused by mutations in a heterogeneous set of genes, all cases present with pathological protein aggregates. We are focused on understanding the initial steps of this protein misbehavior in the hope to find novel therapeutic strategies to halt these devastating diseases in their early stages.
Selected publications
Boeynaems S#, Dorone Y, Zhuang Y, Shabardina V, Huang G, Anca M, Kim G, Sanyal A, Sen N-E, Griffith D, Docampo R, Lasker K, Ruiz-Trillo I, Auburger G, Holehouse AS, Kabashi E, Lin Y, Gitler AD#. Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates. Molecular Cell 2023. co-corresponding
Fumagalli F*, Young FL*, Boeynaems S*, De Decker M, Mehta A, Swijsen A, Fazal R, Guo W, Moisse M, Beckers J, Dedeene L, Bhuvaneish TS, Vandoorne T, Madan V, van Blitterswijk M, Raitcheva D, McCampbell A, Poesen K, Gitler AD, Koch P, Vanden Berghe P, Thal DR, Verfaillie C, Chandran S, Van Den Bosch L, Bullock S, Van Damme P. C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility. Science Advances 2021, vol. 7(15), eabg3013. co-first
Fazal R, Boeynaems S, Swijsen A, De Decker M, Fumagalli L, Moisse M, Vanneste J, Guo W, Boon R, Vercruysse T, Eggermont K, Swinnen B, Beckers J, Pakravan D, Vandoorne T, Vanden Berghe P, Verfaillie CM, Van Damme P. HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. The EMBO Journal, vol. 40, e106177.
Tazelaar GHP*, Boeynaems S*, De Decker M*, van Vugt JJFA, Kool L, Goedee HS, McLaughlin RL, Sproviero W, Iacoangeli A, Moisse M, Jacquemyn M, Daelemans D, Dekker AM, van der Spek RA, Westeneng HJ, Kenna KP, Assialioui A, Da Silva N, Project MinE ALS Sequencing Consortium, Povedano M, Mora Pardina JS, Hardiman O, Salachas F, Millecamps S, Vourc’h P, Corcia P, Couratier P, Morrison KE, Shaw PJ, Shaw CE, Pasterkamp RJ, Landers JE, Van Den Bosch L, Robberecht W, Al-Chalabi A, van den Berg LH, Van Damme P, Veldink JH, van Es MA. ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization. Brain Communications, fcaa064. co-first
Gittings L, Boeynaems S, Lightwood D, Clargo A, Topia S, Nakayama L, Troakes C, Mann D, Gitler AD, Lashley T, Isaacs A. Symmetric dimethylation of poly-GR correlates with disease duration in C9orf72 FTLD and ALS and reduces poly-GR phase separation and toxicity. Acta Neuropathologica, vol. 139, p. 407–410.
Bogaert E*, Boeynaems S*, Kato M, Guo L, Caulfield TR, Steyaert S, Scheveneels W, Wilmans N, Haeck W, Hersmus N, Schymkowitz S, Rousseau F, Shorter J, Callaerts P, Robberecht W, Van Damme P, Van Den Bosch L. Molecular dissection of FUS points at synergistic effect of low-complexity domains in toxicity. Cell Reports, vol. 24(3), p. 529-537. co-first, co-corresponding
featured on the cover
Boeynaems S, Bogaert E, Kovacs D, Konijnenberg A, Timmerman E, Volkov A, Guharoy M, De Decker M, Jaspers T, Ryan VH, Janke AM, Baatsen P, Vercruysse T, Kolaitis RM, Daelemans D, Taylor JP, Kedersha N, Anderson P, Impens F, Sobott F, Schymkowitz J, Rousseau F, Fawzi NL, Robberecht W, Van Damme P, Tompa P, Van Den Bosch L. Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics. Molecular Cell, vol. 65(6), p. 1044-1055.
featured on the cover
Boeynaems S*, Bogaert E*, Michiels E, Gijselinck I, Sieben A, Jovicic A, De Baets G, Scheveneels W, Steyaert J, Cuijt I, Verstrepen KJ, Callaerts P, Rousseau F, Schymkowitz J, Cruts M, Van Broeckhoven C, Van Damme P, Gitler AD, Robberecht W, Van Den Bosch L. Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD. Scientific Reports, vol. 6, article number: 20877. co-first