Research team

Expertise

Neuropathology of human and animal nervous system, immunohistochemistry of nervous system specific proteins, immunodiagnosis of cerebrospinal fluid, enzyme linked immunoassay protein TAU and amyloid-beta, immunoblotting of 14-3-3.

Multidimensional analysis of the nervous system in health and disease (µNeuro). 01/01/2020 - 31/12/2025

Abstract

Neuropathological research is an interdisciplinary field, in which imaging and image-guided interventions have become indispensable. However, the rapid proliferation of ever-more inquisitive technologies and the different scales at which they operate have created a bottleneck at the level of integration, a) of the diverse image data sets, and b) of multimodal image information with omics-based and clinical repositories. To meet a growing demand for holistic interpretation of multi-scale (molecule, cell, organ(oid), organism) and multi-layered (imaging, omics, chemo-physical) information on (dys)function of the central and peripheral nervous system, we have conceived μNEURO, a consortium comprising eight established teams with complementary expertise in neurology, biomedical and microscopic imaging, electrophysiology, functional genomics and advanced data analysis. The goal of μNEURO is to expedite neuropathological research and identify pathogenic mechanisms in neurodevelopmental and -degenerative disorders (e.g., Alzheimer's Disease, epilepsy, Charcot-Marie-Tooth disease) on a cell-to-organism wide scale. Processing large spatiotemporally resolved image data sets and cross-correlating multimodal images with targeted perturbations takes center stage. Furthermore, inclusion of (pre)clinical teams will accelerate translation to a clinical setting and allow scrutinizing clinical cases with animal and cellular models. As knowledge-hub for neuro-oriented image-omics, μNEURO will foster advances for the University and community including i) novel insights in molecular pathways of nervous system disorders; ii) novel tools and models that facilitate comprehensive experimentation and integrative analysis; iii) improved translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds; iv) improved visibility, collaboration and international weight fueling competitive advantage for large multi-partner research projects.

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  • Research Project

Effect of hearing loss and vestibular decline on cognitive function in older subjects: correlation with cortical auditory evoked potentials and mri brain volume changes. 01/01/2019 - 31/12/2022

Abstract

The world population has been aging dramatically, with 12% aged 60 years or older, and a rising number developing dementia. Yet, until now no cure or therapy to slow down the disease has been identified. Recent studies have established that hearing loss increases the risk for developing dementia. Because hearing loss can be treated with a hearing aid or cochlear implantation, this could potentially delay the onset of dementia. Many studies have reported improvement in cognition after hearing rehabilitation, but this might have been caused by just hearing the mostly verbal tests better. Many studies have demonstrated that balance organ function, located in the inner ear, also has an effect on cognition. However, while hearing loss and balance organ function loss often occur simultaneously, it has not been systematically evaluated in older adults. Our aim is to study the effect of hearing loss and balance organ function loss on learning and memory (i.e. cognition) in older subjects (55 years or older) and patients with mild cognitive impairment and Alzheimer's disease. We will do so by systematically evaluating hearing and vestibular function in these subjects, by using a cognitive assessment tool that is adapted to a potentially hearing impaired population, by using objective measurements of electrical activity in the auditory cortex evoked by sound and by analyzing MRI volume changes in relevant areas of the brain to detect who is at risk for developing cognitive impairment.

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  • Research Project

Towards patient-tailored treatment in multiple sclerosis: a dendritic cell-based vaccine for the treatment of multiple sclerosis. 01/10/2018 - 30/09/2020

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which the body 's own immune system attacks the myelin sheath. This leads to disruption in signaling in the brain and spinal cord and to loss of brain tissue. MS is the most common cause of non-traumatic disability in young adults. To date, many aspecific immunomodulatory and general immunosuppressive treatments are used to slow down the disease course, but these treatments have several side effects, ranging from mild to severe and life-threatening issues, including other autoimmune diseases and infections. Thus, there remains an unmet need for specific treatments with a good safety profile. Restoring antigen specific tolerance is an interesting approach to tackle these problems. Theoretically, a limited number of vaccinations with tolerogenic dendritic cells (tolDC) could reeducate the patient's own immune system in the longterm. Based on our previous research in the laboratory on MS and clinical studies in other autoimmune diseases we are ready to bring tolDC treatment to MS patients. The aim of this project is to assess safety and feasibility of autologous myelin-peptide-loaded tolDC in active MS patients, who will receive 6 vaccinations in a phase I clinical trial. Safety will be evaluated by recording of adverse events. Feasibility will be determined by successful production of tolDC. Positive results can lead to clinical trials evaluating efficacy.

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  • Research Project

Towards a "negative" cellular vaccine for the treatment of multiple sclerosis: counter-acting epitope spreading for long-lasting tolerance induction using mRNA-electroporated tolerogenic dendritic cells. 01/01/2016 - 30/09/2018

Abstract

Multiple sclerosis (MS) is an inflammatory disease that affects 1 out of 1000 people in Europe. MS is mediated by an autoimmune response to components or antigens of the insulating cover of the nerves of the central nervous system, i.e. myelin antigens, which are no longer recognised as being 'self'. This causes progressive destruction of the nerves of the brain and spinal cord, presenting as a wide range of motor and sensory disturbances. On the basis of our recent research, we hypothesise that specific cells of the immune system, i.e. dendritic cells (DC), regulate the immune response by inducing immunity or tolerance towards specific antigens. Therefore these DC might be used to suppress abnormal immune responses in autoimmune diseases such as MS. The final aim will be to induce tolerance to myelin antigens by administering DC to MS patients, which might lead to a change in the natural course of the disease. Several techniques exist for the loading of DC with specific antigens, which makes them tolerance inducing for specific autoimmune responses rather than being overall immunosuppressive. We will compare two of these techniques, in combination with a dose escalation vaccine study in MS patients in order to ensure patient safety when administrating a vaccine with tolerance-inducing DC. Patients will be divided in two groups, comparing both antigen-loading strategies by evaluating adverse events, relapse-free interval and immunological response after vaccination.

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    • Research Project

    An integrated approach towards understanding the pathogenesis of neurodegeneration (NEUROBRAINNET). 01/04/2012 - 31/12/2017

    Abstract

    We aim to establish an integrated network to identify genes and proteins involved in neurodegenerative disorders, determine their biological functions, establish their role in the pathophysiological processes, identify modifiers of the function by genetic screens, The network meets the prerequisites for such a project: frontline research in functional genomics related to human health, creating synergies with and between research efforts, teaming up with clinical groups through translational research for providing novel avenues for diagnosis, prevention, treatment and providing training and mobility to improve the skills of our young researchers.

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      • Research Project

      Clinical and genetic epidemiology of Parkinson's disease: focus on disease progression and non-motor symptoms. 01/10/2011 - 30/09/2012

      Abstract

      Parkinson's disease (PD) is the second most common neurodegenerative brain disorder. Five causal genes (SNCA, LRRK2, PARK2, PINK1 and DJ1) leading to familial PD have already been identified. Variations in these genes have also been shown to increase susceptibility for sporadic PD. In my project, I am prospectively recruiting a population of familial and sporadic PD patients. Detailed phenotypic characterization of the patients is performed with standardized clinical scales at different time intervals. Genetic variations (simple and complex mutations) in the known causal genes will be identified and genotype-phenotype correlations will be established. Since disease progression is an important part of the phenotypic variability of PD, these correlations will focus on clinical features associated with disease progression, non-motor symptoms and motor complications. Genetic association studies will be conducted to identify new genetic risk factors for PD. In informative families new causal PD genes will be identified using a positional cloning strategy. The combination of objective and longitudinal clinical data on disease progression in a genetically well-characterized population of PD patients, is a major asset of the project.

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      • Research Project

      Effect of aerobic exercise in improving physical fitness and daily functioning for patients with post-stroke hemiplegia. 01/01/2010 - 31/12/2011

      Abstract

      Many stroke survivors have residual physical impairments that may lead to a sedentary lifestyle and consequently a decline in cardiorespiratory fitness. Research is needed to determine the optimal protocol to train individuals with different levels of physical impairment and cardiac risk. It is useful to know the long-term effects of aerobic exercise training as well as the relationship between improvement in aerobic capacity and daily function.

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      • Research Project

      Clinical and genetic epidemiology of Parkinson's disease: focus on disease progression and non-motor symptoms. 01/10/2009 - 30/09/2011

      Abstract

      Parkinson's disease (PD) is the second most common neurodegenerative brain disorder. Five causal genes (SNCA, LRRK2, PARK2, PINK1 and DJ1) leading to familial PD have already been identified. Variations in these genes have also been shown to increase susceptibility for sporadic PD. In my project, I am prospectively recruiting a population of familial and sporadic PD patients. Detailed phenotypic characterization of the patients is performed with standardized clinical scales at different time intervals. Genetic variations (simple and complex mutations) in the known causal genes will be identified and genotype-phenotype correlations will be established. Since disease progression is an important part of the phenotypic variability of PD, these correlations will focus on clinical features associated with disease progression, non-motor symptoms and motor complications. Genetic association studies will be conducted to identify new genetic risk factors for PD. In informative families new causal PD genes will be identified using a positional cloning strategy. The combination of objective and longitudinal clinical data on disease progression in a genetically well-characterized population of PD patients, is a major asset of the project.

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      • Research Project

      The legal and moral status of human substances, in particular organs and human tissues. 01/07/2009 - 30/06/2013

      Abstract

      Human bodily material, like blood, sperm, egg cells, organs and tissues, is very useful for therapeutic and research purposes. The goal of this project is to examine the legal and ethical statute of removed human bodily material, the pro's and con's of a commercialization of human bodily parts and to investigate the role of the state.

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      • Research Project

      A prospective study examining the role of sensory-motor incongruence on the transition from acute to chronic whiplash-associated disorders. 01/07/2009 - 30/06/2013

      Abstract

      The purpose of this study is to examine whether a prolonged conflict between motor activity and sensory feedback triggers sensitization of the central nervous system, and whether it plays an aetiological role in the transition from acute to chronic whiplash pain. Study participants will enter a 6-months prospective longitudinal study. They will examined at 3 different occasions (within 2 weeks after the whiplash trauma, and 2 and 6 months post-whiplash).

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      • Research Project

      Clinical and preclinical research of the effect of cellular mediators on the modulation of pathogenic responses in multiple sclerosis. 01/01/2009 - 31/12/2012

      Abstract

      In this project, we want to further investigate and exploit the capacity of DC and Treg to correct or modulate pathogenic responses in MS patients. Current research will provide the foundation for the eventual development of a cellular vaccine for the treatment of MS. Depending on the results of this study it can be envisaged to treat patients suffering from MS with tolerogenic DC and/or immunosuppressive Treg in order to eliminate or inactivate autoreactive T cells.

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        • Research Project

        Flexible mathematical and statistical models for microbiological risk assessment. 01/01/2005 - 31/12/2008

        Abstract

        This experiment is part of a larger interdisciplinary project in order to model complex data structures and the accompanying theoretical reference for reliable inferences. The project will implement flexible and reliable statistical models for the microbiological risk evaluations for zoonoses in the food chain.

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        • Research Project

        Differentiation from stem cells to functional neuron cell: in vitro and in vivo model for the treatment of traumatic brain and spinal injuries of children. 01/07/2003 - 30/06/2007

        Abstract

        Researcher(s)

        • Promoter: Jorens Philippe
        • Co-promoter: Berneman Zwi
        • Co-promoter: Buytaert Philippe
        • Co-promoter: Cras Patrick
        • Co-promoter: Delbeke Luc
        • Co-promoter: Van Bockstaele Dirk
        • Co-promoter: Van Bogaert Pierre-Paul
        • Co-promoter: Van Tendeloo Vigor
        • Co-promoter: Verlooy Jan

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        • Research Project

        Phosphorylation of the microtubule associated protein tau in Creutzfeldt-Jacob. 01/01/2002 - 31/12/2005

        Abstract

        Creutzfeldt-Jakob disease (CJD) belongs to the prion diseases and its pathogenesis shows some similarities with Alzheimer's disease (AD). Phosphorylated protein tau is found both in AD and CJD. The project examines the phosphorylation of tau in vitro and in an animal model.

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        • Research Project

        Analysis of the 14-3-3 protein and the tau phosphorylation metabolism with regards to the differential diagnosis of Creutzfeldt-Jakob's disease in an early clinical phase. 01/10/2001 - 30/09/2004

        Abstract

        Creutzfeldt-Jakob's disease (CJD) is a human transmissible spongiform encephalopathy that is caused by an abnormal conformation of the prion protein (PrPsc) and is characterized by progressive dementia, myoclonus and other neurological symptoms. The present project investigates the mechanisms of tau phosphorylation in CJD, the detection of free radical formation, phosphorylation of tau in a scrapie model and differentiation of 14-3-3 isoforms.

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        • Research Project

        Gene environment interaction in Parkinson's disease. 01/10/2000 - 30/09/2001

        Abstract

        Parkinson's disease is probably caused by a neurotoxic influence on a vulnerable substantia nigra. Our investigation involves the detection of risk factors for the disease.

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          • Research Project

          Development and quality control of diagnostic tests in cerebrospinal fluid, brain and lymphoid tissue of patients with Creutzfeldt-Jakob's disease. 01/10/1999 - 30/09/2001

          Abstract

          Creutzfeldt-Jakob's disease is a rare dementia which can only be diagnossed with certainty after autopsy. The project involves the development and implementation of diagnostic tests.

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            • Research Project

            Correlation between in vivo biological markers and neuropathology in dementia 01/10/1999 - 31/05/2001

            Abstract

            Alzheimer's disease is the most frequent cause of dementia, but vascular abnormalities, dementia with Lewy bodies and fronto-temporal dementia are other significant causes. Through the development of diagnostic criteria, systematic use of imaging techniques and functional imaging, the reliability of the clinical diagnosis has increased. In recent years, our investigations have focused on the detection of biological markers in cerebrospinal fluid (CSF) and plasma. In the CSF of Alzheimer patients an increased concentration of the microtubule associated protein tau, the most important constituent of neurofibrillary tangles and a decreased concentration of the A? amyloid protein, a polypeptide that is found in senile plaques. This project will examine the correlation between the neuropathological changes found at autopsy and the alterations in biological markers.

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              • Research Project

              Gene environment interaction in Parkinson's disease. 01/10/1998 - 30/09/2000

              Abstract

              Parkinson's disease is probably caused by a neurotoxic influence on a vulnerable substantia nigra. Our investigation involves the detection of risk factors for the disease.

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                • Research Project

                Retrospective and prospective study of Creutzfeldt-Jakob disease in Belgium. 01/10/1998 - 31/12/1999

                Abstract

                Creutzfeldt-Jakob disease is a rare dementia disease and can only be diagnosed with certainty by neuropathological examination. Our investigation involves clinical symptoms, neuropathology and the study of cerebrospinal fluid.

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                  • Research Project

                  Development and quality control of diagnostic tests in cerebrospinal fluid, brain and lymphoid tissue of patients with Creutzfeldt-Jakob's disease. 01/10/1997 - 30/09/1999

                  Abstract

                  Creutzfeldt-Jakob's disease is a rare dementia which can only be diagnossed with certainty after autopsy. The project involves the development and implementation of diagnostic tests.

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                    • Research Project

                    Biological markers in cerebrospinal fluid : determination of the microtubule protein tan and synaptic proteins in Alzheimer's disease. 01/01/1997 - 31/12/1998

                    Abstract

                    Elevated concentrations of the microtubule associated protein tan have been described in Alzheimer's disease. Determination of synaptic proteins in the cerebrospinal fluid may aid the diagnosis.

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                      • Research Project

                      Influence of phosphorylation on the metabolism of amyloid procursor protein. 30/09/1995 - 31/12/1996

                      Abstract

                      Neurofibrillary tangles and amyloid are the main structural lesions in Alzheimers disease. In well deforced circumstances, LA-N-5 neuroblastoma cells express epitopes of neurofibrillary tangles. The metabolism of amyloid precursor protein in these circumstances is investigated.

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                        • Research Project

                        Cloning of the chromosome 14q24.3 gene for familial presenile Alzheimer dementia. 01/01/1995 - 31/12/1998

                        Abstract

                        This project aims at isolating the gene and identifying the mutation responsible for chromosome 14 encoded presenile Alzheimer dementia. First the candidate region at 14q24.3 will be cloned in YACs and cosmids. Next candidate genes will be isolated using direct cDNA selection and exon amplification techniques. These genes will be analysed for mutations in order to identify the disease gene.

                        Researcher(s)

                        • Promoter: Van Broeckhoven Christine
                        • Co-promoter: Cras Patrick
                        • Co-promoter: Hendriks Lydia
                        • Co-promoter: Martin Jean-Jacques

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                          • Research Project

                          Study of the endogenous and exogenous phosphorylation of astrocyte-secreted proteins. 01/01/1994 - 31/12/1997

                          Abstract

                          The study is focused on the effects of protein phosphorylation on the properties of factors involved in the interaction between neuronal and glial cells. The ecto- and exokinases, and their substrates will be purified and identified by aminoacid sequencing.

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                            • Research Project

                            Influence of phosphorylation on the metabolism of amyloid procursor protein. 01/01/1993 - 31/12/1993

                            Abstract

                            Neurofibrillary tangles and amyloid are the main structural lesions in Alzheimers disease. In well deforced circumstances, LA-N-5 neuroblastoma cells express epitopes of neurofibrillary tangles. The metabolism of amyloid precursor protein in these circumstances is investigated.

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                              • Research Project

                              01/01/1991 - 31/12/1991

                              Abstract

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                                • Research Project