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Diether Lambrechts
Complex Genetics
VIB Vesalius Research Center,  K.U.Leuven


Bio-Ir: Univ. of Leuven, Leuven, Belgium, '99
PhD: Univ. of Leuven, Leuven, Belgium, '03
Postdoc: Vesalius Research Center, Univ. of Leuven, Leuven, Belgium, '03-'07
Postdoc: Wellcome Trust Center, Oxford, UK, '07
VIB Group leader since january '08

e-mail
phone +32 16 346 176
ADDRESS


Current team members
Group leader: Diether Lambrechts
Postdoctoral scientist: Joke Reumers
Ph.D. Students: Bart Claes, Betül Yesilyurt, Ian Buysschaert, Joke Dhondt, Katrien Raes
Support personnel: Dominiek Smeets, Gilian Peuteman, Sofie Van Soest

Keywords
neurodegeneration, VEGF, complex genetics, translational research

Science
Recently and unexpectedly, several molecules with angiogenic activity have been causally implicated in neurodegeneration, thus revealing an intriguing and very relevant connection between angiogenic factors and neurodegeneration. The first angiogenic factor implicated in neurodegeneration was VEGF. By applying a large number of gene-targeted and experimental animal model systems, we now aim to generate fundamental knowledge on the mechanisms of neurodegeneration and the role of ‘so-called’ angiogenic factors herein. More specifically, we intend to explore whether these angiogenic molecules influence neurodegeneration by acting on the neurovasculature, or rather by acting as pleiotrophic factors, modulating neuro-inflammatory responses and exerting protective effects on neurons. We will also carefully assess the therapeutic potential of these novel molecules in various neurodegenerative models (e.g. motor neuron degeneration and neuropathic models) and assess whether other well-established angiogenic factors play a previously unrecognized role in neurodegenerative disease.
In recent years, innovative technologies have been key in allowing the field of complex genetics to move rapidly forward, such that, nowadays, genetic studies are providing the basis for many of the major advances in biology and medicine. Indeed, a myriad of genetic and molecular modifications, such as single nucleotide variations (SNPs), epigenetic changes (e.g. DNA methylation) and non-coding RNAs (microRNA), are found to importantly regulate gene expression and to induce a variety of complex human traits and disease diversities. In the past, the Vesalius Research Centre (VRC) has significantly invested in animal model systems to perform functional genetic studies (zebrafish, tadpoles and mice). However, model organisms do not always reflect what really happens in human disease. We therefore aim to translate our animal genetic findings in humans by generating conclusive genetic evidence in human disease. By applying an opposite strategy, we also aim to identify novel and clinically-relevant disease genes, which will then be studied in our classical animal models to unravel the mechanisms by which these genes cause human disease, and also assess their therapeutic potential. To this extent, a number of collaborations have been initiated with clinicians in the University Hospital in Leuven, and large-scale DNA collections of patients included in clinical trials or databases are currently ongoing.

Press Releases:
See also press release (01/12/2008): First trial in patients with a potential treatment of the incurable ALS muscle disease.


Selected Publications



Lambrechts D, Poesen K, Fernández-Santiago R, Al-Chalabi A, Del Bo R, Van Vught P, Khan S, Marklund S, Brockington A, Van Marion I, Anneser J, Shaw C, Ludolph A, Leigh N, Comi G, Gasser T, Shaw P, Morrison K, Andersen P, Van Den Berg L, Thijs V, Siddique T, Robberecht W, Carmeliet P
Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype
J MED GENET 46, 840-6, 2009



Zacchigna S, Lambrechts D, Carmeliet P
Neurovascular signalling defects in neurodegeneration
NAT REV NEUROSCI 9, 169-81, 2008



Lambrechts D, Robberecht W, Carmeliet P
Heterogeneity in motoneuron disease
TRENDS NEUROSCI 30, 536-44, 2007



Storkebaum E, Lambrechts D, Dewerchin M, Moreno Murciano M, Appelmans S, Wang I, Van Damme P, Rutten B, Man W, De Mol M, Wyns S, Manka D, Vermeulen K, Van Den Bosch L, Mertens N, Schmitz C, Robberecht W, Conway E, Collen D, Moons G, Carmeliet P
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS
NAT NEUROSCI 8, 85-92, 2005



Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, Marklund l, Wyns S, Thijs V, Andersson J, Van Marion I, Al-Chalabi A, Bornes S, Musson R, Hansen V, Beckman L, Adolfsson R, Pall s, Prats H, Vermeire S, Rutgeerts P, Katayama S, Awata T, Leigh N, Lang-Lazdunski L, Dewerchin M, Shaw C, Moons G, Vlietinck R, Morrison e, Robberecht W, Van Broeckhoven C, Collen D, Andersen m, Carmeliet P
VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death
NAT GENET 34, 383-394, 2003







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