Projects
Rational discovery of drug compounds targeting the chromatin-reading function of LEDGF/p75 towards the treatment for acute MLL-rearranged leukemia KU Leuven
Mixed-lineage leukemia rearranged (MLL-r) is an acute leukemia mostly affecting children and associated with poor survival. The disease is caused by rearrangements in the MLL gene resulting in malignant fusion proteins. LEDGF/p75 serves as an epigenetic reader and tethers transcription complexes containing MLL to chromatin via its PWWP domain. Recent studies demonstrated that this process is essential for the onset of MLL-r leukemia, yet it ...
Development and validation of a repurposing platform for drug discovery to treat cardiomyopathy. KU Leuven
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. A subset of CVDs that remain particularly challenging to treat are cardiomyopathies (CMs) or ‘diseases of the heart muscle’. CMs are heterogeneous in origin and phenotype and mostly caused by an ever increasing number of gene mutations. The long-term benefits of current generalised pharmacological approaches are uncertain and these drugs only relieve symptoms instead of ...
Target validation and drug discovery towards a therapy for the Rett Syndrome. KU Leuven
Rett syndrome (RTT) (OMIM 312750) is a progressive neurodevelopmental disorder that predominantly affects girls and is caused by loss-of function mutations in the methyl-CpG-binding protein 2 (MeCP2). To date only symptomatic treatment is available. In this project we will validate on the one hand the direct interaction between the transcriptional co-activator lens epithelium-derived growth factor p75 (LEDGF/p75) and MeCP2 as a putative ...
Translational Platform for MSA: Elucidation of Disease-mechanisms and Drug discovery KU Leuven
Objectives:
(i) Generation of MSA-specific iPSC from MSA fibroblasts collected at FCRB and then differentiated into oligodendrocytes (OD).
(ii) Examination of changes in fibroblasts and iPSC-OD of MSA patients versus controls at the transcriptomic, epigenomic and proteomic levels.
(iii) To study the uptake and seeding propensity of structurally distinct α-syn fibrillar forms (amplified from MSA brain) in MSA-derived iPSC-OD. ...
Genome-wide genotype-phenotype associations in Drosophila for neurodegenerative disease pathway and drug target discovery. KU Leuven
The increase in life expectancy in the Western world has seen a growing number of individuals suffering from neurodegenerative disorders. Many of these disorders are associated with the accumulation of toxic protein species, such as amyloid beta (aß) peptides in Alzheimer’s disease (AD), microtubule-binding Tau in AD and frontotemporal lobe degeneration (FTLD), a-synuclein in Parkinson’s disease (PD), and TDP-43 in amyotrophic lateral ...
Spatially-Organized 3D Human Cardiac Bilayer Models for Duchenne Cardiomyopathy Modelling and Drug Discovery KU Leuven
Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterized by DYSTROPHIN (DYS) deficiency. DYS is a sarcolemmal protein which mainly links the cytoskeleton to the extracellular matrix (ECM), by interacting with the dystrophin glycoprotein complex (DGC). Dilated Cardiomyopathy (DC) represents the major cause of death in late-stage DMD patients. In addition, DMD patients often develop left ventricular ...
Establishing Microfluidic Spatial Multidimensional Technology to Revolutionize the Post-genomic Discovery of Immunotherapeutic Strategies Enabling Novel Drug Development Vrije Universiteit Brussel
Autonomous Drug Discovery: Machine Learning for Optimization of Computer-Aided Organic Synthesis in Flow Ghent University
Drug discovery is a long and costly process, in which the chemical synthesis of target compounds is a rate-limiting step. Recent academic breakthroughs have introduced artificial intelligence and robotics for drug discovery. Potential drug candidates can now be discovered by machine learning algorithms, a feasible synthesis pathway for compounds is predictable using large datasets and robots can perform automated synthesis. However, ...
Experimental evolution in Candida biofilms: does drug tolerance facilitate drug resistance development in fungi?Experimental evolution in Candida biofilms: does drug tolerance facilitate drug resistance development in fungi? KU Leuven
Invasive fungal infections pose a profound and growing public health threat with treatment failure and mortality estimates often surpassing 50%. Only three major antifungal drug classes are available to treat lethal fungemia and the incidence of resistance to these drugs has risen significantly in recent years. Moreover, multidrug resistant (MDR) ‘superbugs’ like Candida auris have emerged. Despite these alarming concerns, fungal infections ...