Research areas

The Laboratory of Cell Biology and Histology (CBH) is an interfaculty research group, uniting scientists from the Faculty of Biomedical, Pharmaceutical and Veterinary sciences and the Faculty of Medicine and Health Sciences. Their joint mission is to elucidate the cell biological principles of human physiology and disease, so as to expose new entry points for diagnostic and therapeutic strategies.

Core research lines strongly align with key research domains at the University of Antwerp, such as Neurobiology, Oncology, Imaging and Infectious diseases. The research is fueled by solid expertise in cell, tissue and systems biology and finds a common denominator in the use and development of advanced microscopy technology. 

In line with the latter, CBH also operates as the Antwerp Centre for Advanced Microscopy (ACAM), providing high-end microscopy service tailored towards both ultrastructure and live cell-imaging applications. As microscopy hub, CBH is founding member of the Centre of Excellence ‘µNeuro’ and of the former IOF-consortium ‘EGAMI’ and the new IOF-consortium ‘iMARK’ of the University of Antwerp, the University valorisation platform for Imaging.

Key research areas

Translational gut and lung research

Accelerated Aging Diseases

Next-generation Microscopy


Master Thesis Subjects

Cell-intrinsic response to microbial and host-derived amyloids in the enteric nervous system
Tutors: Nouchin De Loose, Peter Verstraelen - Promoters: Jean-Pierre Timmermans, Winnok De Vos

Growing evidence suggest that the gut-brain axis and its regulation by the microbiota may play an essential role in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Mechanisms underlying the cellular effects of amyloids in the enteric nervous system are, however, poorly characterised. This research line focusses on acquiring novel insights into the pro-inflammatory mechanisms in in vitro cultures of  myenteric neurons and glial cells, and the reciprocal interactions between both cell types. To this end, we study the activation of Toll-like receptors and the downstream inflammasome after exposure of the enteric cultures to human and bacterial-derived amyloids. These pathways will be analyzed using a combined approach of immunocytochemistry, ELISA, qPCR and Western blotting. Results obtained in vitro will be validated in vivo by amyloid injections into the colon wall of anesthetized mice.

Key words: Neurodegeneration, Enteric nervous system, Gut-brain axis, Amyloid, Inflammasome


Transmission of amyloid throughout the gut-brain axis, a novel entry point for AD?
Tutor: Rosanne Verboven, Peter Verstraelen - Promoters: Jean-Pierre Timmermans, Winnok De Vos

The peripheral component of neurodegenerative disorders, more specifically the microbiome-gut-brain axis, is attracting attention in the recent years. Patients with Alzheimer’s disease (AD) often experience gastrointestinal symptoms long before the cognitive decline emerges. In this thesis, we will explore whether this is due to the uptake of amyloidogenic proteins trough the gut wall. Given that the intestinal epithelial barrier becomes leakier with age, the major risk factor for AD, we are working in neurodegenerative aging mouse model. To study gut permeability ex vivo, we make use of an advanced setup called the Ussing chambers. In addition, we are investigating whether intramural injections of bacterial amyloids are able to exacerbate central amyloidosis and/or gut permeability. These findings will also be validated using targeted molecular analyses (qPCR, immunoblot) and microscopic assays.

Key words: Neurodegeneration, Enteric nervous system, Gut-brain axis, Amyloid, gut permeability, microscopy


Neuro-Immune communication in the gut and meninges during ageing and inflammation
Tutor: Jasper Van Haver - Promoter: Sales Ibiza Martinez

One of the major concerns in gastrointestinal medicine is to understand how the mucosal environment works.  The ‘rise’ of enteropathies and neuropathies in developed countries can be attributed to an increasingly ageing population, environmental factors, genetic factors, and/or inadequate dietary habits.  The Gastrointestinal (GI) tract is the centre of absorption and secretion, which is essential for growth, digestion, and protection against pathogenic microorganisms. A breakdown of intestinal homeostasis can lead to chronic inflammation, resulting in a decrease or dysfunction of the neurons within the gut wall, impacting gut function and inducing enteric, or central neuropathy. To improve the therapeutic design, we aim to understand how different environments affect neuro-immune communication and how this influences inflammation or health/repair. To achieve this goal, we are identifying the local inter- and intra-cellular networks and which pathways connect with the central neuropathies.

Keywords: Neurodegeneration, Enteric nervous system, Meninges, qPCR, Cell culture, Confocal microscopy, FACS, Bioinformatics


Nuclear envelope stress as a driver in the development of glioblastoma multiforme
Tutor: Sarah Peeters - Promoter: Winnok De Vos

Glioblastoma multiforme (GBM) is one of the most lethal tumors, due to its high heterogeneity, extensive infiltration, and cell state plasticity. Recurrence is almost universal, and there is no cure, thus urging for novel research angles. GBM cells experience significant confinement owing to the high cell density and limited migration space in the brain, which alters their nuclear mechanics and might sensitize them to nuclear envelope (NE) stress. This process promotes DNA damage, which may contribute to genome instability, tumour invasion and aggressiveness. With this project, we will investigate the contribution of NE stress to the development of GBM. First, we will characterize the composition and fragility of the NE in a panel of GBM cells of varying aggressiveness. Next, we will study the short-term and long-term effects of NE stress, which we will induce by mechanical confinement. Finally, we will study this process in a 3D cerebral organoid model.

Key words: Cell biology, Nuclear envelope, Cancer, DNA damage, Live cell imaging

 

Morphological profiling of neuro-spheroids using light-sheet microscopy
Tutor: Sarah De Beuckeleer – Promoter: Winnok De Vos

With the advent of human induced pluripotent stem cell (iPSC) technology, it has now become possible to generate organoids that more faithfully capture part of the heterogeneity and three-dimensional context of human tissue. However, the complexity and optical inaccessibility of such tissue mimics hamper their adoption in a routine screening setting. We are developing an approach for in-depth cellular phenotyping of organoids, using multiplex staining, light sheet microscopy and deep learning. More specifically we intend to apply this approach to neuro-organoids that we grow from iPSC. As first aim, we intend to enable automatic identification and discrimination of the composite cell types (neurons, glia and astrocytes) and characterize their cell state (live, dead or quiescent).

Key words: organoids, morphological phenotyping, image analysis, light-sheet microscopy, neuro-spheroids, deep learning


Tau-induced senescence in human mini-brains
Tutor: Johanna Van Den Daele – Promoter:  Winnok De Vos

Defects in the microtubule associated protein tau typify a range of neurodegenerative disorders termed tauopathies, which includes Alzheimer’s disease. Recent studies point to the potential involvement of cellular senescence, an irreversible non-proliferative state, associated with inflammatory cytokine secretion, in disease development. However, the causality, timing, and afflicted cell types remain poorly characterized. The goal of this project is to define the exact causal relationship between senescence and tauopathy development in a human context. To achieve this, human iPSC-derived brain organoids will be produced, containing the three major cell types of the brain (neurons, astrocytes, or microglia) and the emergence of senescence therein will be assessed using deep coverage microscopy and single cell sequencing. Once a cell-specific senescence signature has been established,  its penetrance in mutant organoids that recapitulate the hallmarks of tau pathology will be measured. Finally, whether senescence-targeting compounds modulate tau pathology and influence organoid condition will be evaluated. Together, this work should allow defining whether senescence is a driving factor in human tau pathology development and unveil its potential as druggable node.


Nuclear envelope stress in laminopathy patient-derived cardiomyocytes (NStrC)
Tutor: Lauran Vandeweyer – Promotor: Winnok De Vos

Dilated cardiomyopathy (DCM) compromises the heart’s essential function of pumping blood through the body and is the primary cause of heart transplants worldwide. Hereditary variants of DCM are driven by mutations in the LMNA gene encoding A-type lamins, which are crucial components of nuclear envelope (NE). We and others have shown that lamin perturbations predispose cells for nuclear dysmorphy and rupture, which compromises cell homeostasis and elicits DNA damage. We hypothesize that this so-called NE stress represents a common hallmark of cardiac laminopathies. Hence, we set out to gauge the impact of pathogenic lamin variants on this process in a cellular model that is relevant to the disease. To this end, we are generating induced pluripotent stem cell-derived cardiomyocytes from cardiac patient fibroblasts harboring diverse LMNA mutations. In these cells, we will quantify structural defects of the NE and its susceptibility to rupture with advanced microscopy. In addition, we will analyze the allover cell fitness and evaluate the influence of major NE stress elicitors by pharmacological modulation. This way, we intend to expose the role of NE stress in the development of cardiac laminopathies and unveil potential leads for its therapeutic targeting.

Key words: Cardiomyopathy, Cell biology, iPSC, nuclear mechanosensing, Microscopy, Nuclear envelope stress


Immune profiling and in vitro modelling for Long Covid
Tutor: Angelina Konnova/An Hotterbeekx – Promoter: Samir Kumar-Singh

There is an increasing number of individuals who do not return to their baseline health after SARS-CoV-2 infection and suffer from symptoms up to 6 months later. During this project the student will investigate patient samples as well as two physiologically relevant in vitro airway model to study the early cellular responses for possible long-term consequences of SARS-CoV-2 infection: The student will measure antibody production, seroneutralizing capacity and cytokine profiles in the serum of patients with Long Covid. In addition, thesis findings will be validated in vitro, namely, air-liquid interface (ALI) cultures and airway organoids. In the first model, primary human bronchial- and alveolar cells will be differentiated on a transwell porous membrane. A second model that will be employed is the differentiation of primary human bronchial and alveolar cells into organoids. The SARS-CoV-2 infections will be performed with our collaborators at the Institute of Tropical Medicine. The cell cultures and organoids will be imaged in toto through life cell imaging and confocal microscopy after fluorescent staining. Gene expression will be explored with quantitative PCR.

Key words: Mesoscale discovery, immune response,  Cell culture, COVID-19, Long Covid microscopy


Diagnostic and prognostic biomarkers in Ventilator associated pneumonia caused by Pseudomonas aeruginosa and Staphylococcus aureus
Tutor: An Hotterbeekx – Promoter: Samir Kumar-Singh

Ventilator associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) is a major contributor to high mortality and morbidity in the intensive care unit. Here we aim to identify host- as well as pathogen-derived biomarkers to predict which patients are at increased risk of developing VAP at the time of hospital admission as well as markers to distinguish which pathogen is causing VAP at the time of diagnosis. To do so, mass spectrometry will be performed on patient samples at the time of tracheal intubation/mechanical ventilation and the day after VAP diagnosis and matched controls. In addition, we will investigate the role of pathogen-derived biomarkers in virulence and host-pathogen interaction in two in vitro airway models: Air-liquid interface (ALI) cultures and airway organoids.

Key words: Proteomics, pneumonia, diagnosis, prognosis, biomarker, Pseudomonas aeruginosa, virulence factors


Hyperthermia as a potential therapy in pancreatic ductal adenocarcinoma treatment
Tutor: Robin Colenbier -  Promoters: John-Paul Bogers and Jean-Pierre Timmermans

Pancreatic ductal adenocarcinoma (PDAC) is the cancer type with the worst prognosis and the highest occurrence of therapy resistance. As a result, patients are in need for novel and efficacious treatments. Initial in vitro and in vivo experiments on the effect of moderate hyperthermia (41.5 °C) have demonstrated synergism between hyperthermal treatment and routinely used chemotherapeutic drugs for PDAC. Nevertheless, most in vitro evaluations have been performed on 2D monocultures. Seeing that pancreatic stellate cells, a type of cancer-associated fibroblasts, play a critical role in the development of PDAC, as well as in the development of resistance towards therapies, they should be included in future research in order to provide more meaningful pre-clinical models. In this project, the student will investigate the effect of hyperthermia on PDAC cells and pancreatic stellate cells, also in combination with routine cancer treatments in order to gain more insight into the potential impact of hyperthermia for PDAC-treatments. Alternatively, the focus could shift towards evaluating non-classical pathways of killing cancer cells (e.g. ferroptosis, senescence induction). Eventually, the knowledge gained via the initial in vitro experiments will be applied in a chicken embryo chorioallantoic membrane (CAM) model.

Key words: pancreatic cancer, pancreatic stellate cells, therapy resistance, hyperthermia, CAM model