After obtaining his master degree in biology, Ludo Van Den Bosch received his PhD in the field of physiology at the KU Leuven (Belgium) in 1990. After postdoctoral positions specializing in molecular biology and neurodegeneration, he co-established the Laboratory of Neurobiology and became assistant professor at the KU Leuven in 2001. He was promoted in 2013 to Full Professor at the Department of Neurosciences. Since 2014, he is also group leader in the VIB Center for Brain & Disease Research (Leuven). In 2017, he took over the directorship of the Laboratory of Neurobiology (Experimental Neurology). The focus of his research is on motor neuron diseases such as amyotrophic lateral sclerosis (ALS), as well as on different neuropathies such as Charcot-Marie-Tooth disease (CMT). The central goal of his research is to understand more in detail the mechanisms of neuronal and axonal degeneration and regeneration and to translate these discoveries into new therapeutic strategies for the different neurodegenerative disorders. Research models range from cell lines, induced pluripotent stem cells (iPSCs) and small animal models including fruit fly and zebrafish to transgenic mouse models for the different neurodegenerative diseases. The main research focus is on the importance of disturbances in intracellular transport processes, including nucleocytoplasmic and axonal transport. In addition, the role of non-neuronal cells such as astrocytes and microglia in these processes is investigated in detail.
“Gain-of-function and loss-of-function effects of iPSC derived astrocytes from ALS patients on human motor units”.
Abstract: Astrocytes play a crucial role in the selective motor neuron pathology in amyotrophic lateral sclerosis (ALS). These cells provide an important neuronal homeostatic support. However, this function is highly compromised in ALS. We established a fully human coculture systems to study the underlying mechanisms of the dysfunctional intercellular interplay. We characterized human induced pluripotent stem cell (hiPSC)-derived astrocytes from FUS-ALS patients and incorporated these cells into a human motor unit microfluidics model to investigate the astrocytic effect on the hiPSC-derived motor neuron network and on the functional neuromuscular junctions (NMJs) using immunocytochemistry and live-cell recordings. FUS-ALS cocultures were systematically compared to their CRISPR-Cas9 gene-edited isogenic control systems. We observed a dysregulation of astrocyte homeostasis, which resulted in a FUS-ALS-mediated increase in reactivity and secretion of inflammatory cytokines. Upon coculture with motor neurons and myotubes, we detected a cytotoxic effect on motor neuron-neurite outgrowth, NMJ formation and functionality, which was improved or fully rescued by isogenic control astrocytes. We demonstrate that ALS astrocytes have both a gain-of-toxicity and loss-of-support function involving the WNT/β-catenin pathway, ultimately contributing to the disruption of motor neuron homeostasis, intercellular networks and NMJs.
