Laboratory of Neurophysiology in Neurodegenerative Disorders

The Laboratory of Neurodegenerative Disorders and Neurophysiology studies the spreading of RNA binding proteins, including FUS and TDP-43, in ALS as well as the role of local axonal translation in neurodegeneration in ALS and FTD. The team also focuses on muscle innervation and the development of new therapeutic targets to treat neuromuscular disorders including ALS. 

Sandrine Da Cruz

Group Leader
VIB Group Leader as of October 1, 2019
Professor Department of Neurosciences KU Leuven - January 2020
Assistant Investigator: Ludwig Cancer Research San Diego Branch, US, 2016-present
Research Scientist: Ludwig Cancer Research San Diego Branch, US, 2013-2015
Post-doc: Ludwig Institute for Cancer Research-University of California San Diego (UCSD), US, 2006-2012
PhD: University of Geneva, Switzerland, 2005

Research areas

Human diseases Structural biology

Research focus

RNA-binding proteins spreading in ALS

Neurodegenerative diseases are characterised by misfolded, fibrillary aggregated forms of disease-related proteins. These aggregated forms self-propagate and spread throughout the nervous system, suggesting that cell-to-cell transmission of pathological proteins contributes to disease progression. However, to date the underlying mechanisms are not established.

RNA binding proteins have emerged as central players in the mechanisms of neurotoxicity underlying many of the most prominent neurodegenerative diseases. In particular, mutations in TDP-43 and FUS cause ALS and frontotemporal dementia (FTD) and are major protein components of pathological inclusions in most ALS cases and half of FTD instances. We study whether and how de-mixing/aggregation of these disease-causing proteins contributes to neurodegeneration, including by spreading within the central nervous system and/or periphery, and if so which cell types and misfolded species drive disease initiation and progression. 

To characterize the relative contribution of neurons and glial cells in FUS spreading, we use co-cultures of hippocampal, cortical or motor neurons and glial cells isolated from humanized FUS mice. We also characterize the structural and biochemical properties of FUS aggregates from patient samples and from ALS-linked FUS mutant proteins. This provides important insights into mechanisms of cell-to-cell spreading which may underlie the source of diversity and cell vulnerability in FUS proteinopathies. 

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Publications

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Jobs

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Team

The Sandrine Da Cruz’ Lab can only thrive thanks to the dedication and commitment of its people, no matter what their function or seniority. 

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Events

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