Research Patrick Cras

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.

Researcher(s)

• Promoter: Sijbers Jan
• Co-promoter: Baets Jonathan
• Co-promoter: Cras Patrick
• Co-promoter: De Vos Winnok
• Co-promoter: Giugliano Michele
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Staelens Steven
• Co-promoter: Stroobants Sigrid
• Co-promoter: Timmerman Vincent
• Co-promoter: Timmermans Jean-Pierre
• Co-promoter: Verhoye Marleen
• Co-promoter: Weckhuysen Sarah

Research team(s)

• Vision lab

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Van Rompaey Vincent
• Co-promoter: Cras Patrick
• Co-promoter: Mertens Griet
• Co-promoter: Van Ombergen Angelique

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cools Nathalie
• Co-promoter: Cras Patrick
• Fellow: Willekens Barbara

Research team(s)

• Laboratory for Experimental Hematology (LEH)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Cools Nathalie
• Co-promoter: Cras Patrick
• Fellow: Derdelinckx Judith

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Cras Patrick
• Co-promoter: Engelborghs Sebastiaan
• Co-promoter: Van Dam Debby

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Crosiers David

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Co-principal investigator: Truijen Steven

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Crosiers David

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Vansweevelt Thierry
• Co-promoter: Cras Patrick
• Co-promoter: Mortelmans Dimitri

Research team(s)

• Personal Rights and Property Rights

Project type(s)

• Research Project

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).

Researcher(s)

• Promoter: Cras Patrick
• Co-principal investigator: Roussel Nathalie

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Van Tendeloo Vigor
• Co-promoter: Berneman Zwi
• Co-promoter: Cools Nathalie
• Co-promoter: Cras Patrick
• Co-promoter: Ponsaerts Peter
• Co-promoter: Ysebaert Dirk

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Fellow: Van Everbroeck Bart

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Pals Philippe

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Fellow: Van Everbroeck Bart

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Fellow: Cras Patrick

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Pals Philippe

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick
• Fellow: Van Everbroeck Bart

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project

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

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Slegers Herman
• Co-promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Cras Patrick

Research team(s)

Project type(s)

• Research Project