Tom Vanden Berghe

Tom Vanden Berghe
University of Antwerp | UA · Department of Biomedical sciences

Professor

About

154
Publications
82,672
Reads
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21,614
Citations
Additional affiliations
March 2017 - present
Ghent University
Position
  • Master's Student
September 2015 - present
Ghent University
Position
  • Titular Integrated praticum Biotechnology - Bachelor 3rd
September 2015 - September 2017
Ghent University
Position
  • Master's Student

Publications

Publications (154)
Article
Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner. Although RIPK1 (receptor-interacting protein kinase 1)- and RIPK3-MLKL (mixed lineage kinase domain-like)-mediated necroptosis is the most understood form of regulated necrosis, other examples of this process are...
Article
Rationale: Sepsis is one of the leading causes of death around the world. The failure of clinical trials to treat sepsis demonstrates that the molecular mechanisms are multiple and are still insufficiently understood. Objectives: To clarify the long disputed hierarchical contribution of several central inflammatory mediators (IL-1 beta, IL-18, casp...
Article
Targeted mutagenesis in mice is a powerful tool for functional analysis of genes. However, genetic variation between embryonic stem cells (ESCs) used for targeting (previously almost exclusively 129-derived) and recipient strains (often C57BL/6J) typically results in congenic mice in which the targeted gene is flanked by ESC-derived passenger DNA p...
Article
High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associa...
Article
Full-text available
The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought...
Article
Full-text available
Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model...
Article
Full-text available
The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferro...
Article
Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables r...
Article
Full-text available
Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune...
Article
Rationale: Necroptosis, mediated by RIPK3 and MLKL, is a form of regulated necrosis that can drive tissue inflammation and destruction, however its contribution to COPD pathogenesis is poorly understood. Objectives: To determine the role of necroptosis in COPD. Methods: Levels of RIPK3, MLKL and activated phospho-MLKL were measured in lung tis...
Article
Full-text available
RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL....
Article
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Radiotherapy is commonly used as a cytotoxic treatment of a wide variety of tumors. Interestingly, few case reports underlined its potential to induce immune-mediated abscopal effects, resulting in regression of metastases, distant from the irradiated site. These observations are rare, and apparently depend on the dose used, suggesting that dose-re...
Article
Full-text available
Lipid peroxidation (LPO) drives ferroptosis execution. However, LPO has been shown to contribute also to other modes of regulated cell death (RCD). To clarify the role of LPO in different modes of RCD, we studied in a comprehensive approach the differential involvement of reactive oxygen species (ROS), phospholipid peroxidation products, and lipid...
Article
Full-text available
The complexity of the ischemic cascade is based on the integrated crosstalk of every cell type in the neurovascular unit. Depending on the features of the ischemic insult, several cell death mechanisms are triggered, such as apoptosis, necroptosis, ferroptosis/oxytosis, ETosis or pyroptosis, leading to reactive astrogliosis. However, emerging evide...
Article
Full-text available
Aims: Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID-19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID-19 lethal cardiogenic shock. Methods and results: We report on a 48-year-old male COV...
Article
Full-text available
Significance: Iron is an essential element required for growth and proper functioning of the body. However, an excess of labile ferrous iron increases the risk of oxidative stress-induced injury due to the high reactivity of the unpaired reactive electrons of both ferrous iron and oxygen. This high reactivity can be exemplified in the outside worl...
Article
Full-text available
The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus...
Article
Friedreich's ataxia (FRDA) is a neurodegenerative disease characterized by an increase in intracytoplasmic iron concentration. Here the nanoscale iron distribution within single fibroblasts from FRDA patients was investigated using synchrotron-radiation-based nanoscopic X-ray fluorescence and X-ray in-line holography at the ID16A nano-imaging beaml...
Chapter
Ferroptosis is essentially an iron-catalyzed process of excessive lipid peroxidation. This clinically relevant mode of regulated necrosis is highly studied in an attempt to control it. Synthetic lipophilic free radical traps block ferroptosis and are now preclinically explored for their effectiveness to treat degeneration, trauma, and organ injury....
Article
Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for innovative cancer drug development. Reverse pharmacology approaches of Withania somnifera leaves and...
Article
One of the key challenges in cancer research is how to effectively kill cancer cells while leaving the healthy cells intact. Cancer cells often have defects in cell death executioner mechanisms, which is one of the main reasons for therapy resistance. To enable growth, cancer cells exhibit an increased iron demand compared with normal, non-cancer c...
Article
Apoptosis is a highly regulated process involved in the normal organism development and homeostasis. In the context of anticancer therapy, apoptosis is also studied intensively in an attempt to induce cell death in cancer cells. Caspase activation is a known key event in the apoptotic process. In particular, active caspase-3 and -7 are the common e...
Article
Full-text available
Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms of RCD have been identified and are increasingly being implicated in various h...
Article
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NF-κB (nuclear factor κB) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-κB, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-κB transcription, had no impact upon thymocyte development....
Article
Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue t...
Article
Full-text available
Clostridium difficile is the leading cause of pseudomembranous colitis in hospitalized patients. C. difficile enterotoxins TcdA and TcdB promote this inflammatory condition via a cytotoxic response on intestinal epithelial cells (IECs), but the underlying mechanisms are incompletely understood. Additionally, TcdA and TcdB engage the Pyrin inflammas...
Article
To cope with the poor aqueous solubility of withaferin A, a broad-spectrum anti-cancer agent effective against therapy-resistant cancers, a polymer-drug conjugate was synthesized via a grafting-from-drug approach. Modification of withaferin A at the C27-OH with a chain transfer agent (CTA) for reversible addition-fragmentation chain transfer (RAFT)...
Article
In this issue of Molecular Cell, Ying et al. (2018) report on a novel function of MLKL in sciatic nerve regeneration after injury through myelin sheath destabilization. This function of MLKL is independent of necroptosis execution and requires phosphorylation at MLKL-S441.
Article
Full-text available
Ferroptosis is an iron-catalysed, non-apoptotic form of regulated necrosis that results in oxidative lipid damage in cell membranes that can be inhibited by the radical-trapping antioxidant Ferrostatin-1 (Fer-1). Novel inhibitors derived from the Fer-1 scaffold inhibited ferroptosis potently but suffered from solubility issues. In this paper, we re...
Article
Full-text available
Current clinical diagnosis is typically based on a combination of approaches including clinical examination of the patient, clinical experience, physiologic and/or genetic parameters, high-tech diagnostic medical imaging, and an extended list of laboratory values mostly determined in biofluids such as blood and urine. One could consider this as pre...
Conference Paper
Ferroptosis is an iron dependent form of necrosis, involved in different pathologies such as kidney failure and neurodegenerative diseases. Glutathione peroxidase 4 (GPX4) is the central enzyme protecting the cell from ferroptosis. High-throughput screening led to the discovery of ferrostatin-1 (Fer-1) as a potent in vitro inhibitor of ferroptosis....
Article
Full-text available
Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation can directly repress TNF-induced death. Here, we show that ubiquitylation regulates RIPK1's cyto...
Article
Full-text available
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated c...
Preprint
Full-text available
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated c...
Article
Full-text available
Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis can visualize trace level elemental distribution in a fully quantitative manner within single cells. However, in-air XRF analysis requires chemical fixation modifying the cell’s chemical composition. Here, we describe first nanoscopic XRF analysis upon cryogenically fr...
Data
Incoming count rate (ICR) and outgoing count rate (OCR) map from scan on FRDA fibroblast case ‘DJS’ for detector 0,1,2,3,4 and 5. For each detector, the corresponding dead time map is shown. (TIF)
Data
Relative LODs obtained for NIST SRM 1577C ‘bovine liver’ at beamline ID16A-NI for different number of detectors used. LODs were calculated in ‘High Dose’ mode. Relative LOD is calculated for integrated signal from all 6 detector (blue), integrated detector signal from detectors no. 3-4-5 (orange) and from detector no. 5 only (grey). Colored curves...
Data
Elemental maps of Si, P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Au and Compton/Rayleigh scatter of FRDA fibroblast case ‘DJS’ obtained for each SDD detector (0, 1, 2, 3, 4 and 5) separately. The total scanned area covers 44.9 x 32.7 μm2. Elemental maps were obtained at ‘High dose’, using a step size of 55 nm and a dwell time of 55 ms. Elemental...
Data
Elemental maps of iron and potassium of FRDA fibroblast case ‘DJS’ for detector no. 3, 4 and 5. The total scanned area covers 44.9 x 32.7 μm2. Elemental maps were obtained at ‘High dose’, using a step size of 55 nm and a dwell time of 55 ms. Cell border and nucleus are indicated on the iron elemental map of detector no. 5 for clarity using a dashed...
Data
Total absorption cross-section μi of pure ice (blue curve) and within NIST SRM 1577C ‘bovine liver’ (red curve). Results are expressed in cm2/g. A curve was added to ‘guide the eye’. The total absorption cross-section of the incoming photon energy (17 keV) within both matrices (ice, bovine liver) was determined as well. (TIF)
Data
Quantification workflow illustrated for a XRF map of a human FRDA fibroblast case ‘DJS’. From the incoming (ICR) and outgoing count rate map (OCR), the dead time percentage map is determined (in %). Together with the I0 map (in a.u.) and the raw element intensity maps (in cts), normalized element intensity maps are produced (in cts/s). Using the Fu...
Data
Elemental distributions of K, Ca, Fe, Zn and Compton scattering in NIST SRM 1577C ‘bovine liver’. Elemental maps were obtained under cryogenic conditions at ID16A-NI ‘Nano-imaging’ beamline at the ESRF in Grenoble (France). ‘High dose’ mode, pixel size: 250 nm (a) and 25 nm (b), 100 ms dwell time. (TIF)
Data
Correction factors when determining the elemental concentrations within a single cell covered by an ice layer using the Fundamental Parameter equation and NIST SRM 1577C as calibration standard. Correction factor for self-absorption in NIST SRM 1577C (blue), in ice (blue) and total absorption correction factor (green). (TIF)
Data
Relative, areal, molar, absolute and atomic LODs obtained at beamline ID16A-NI for P, S, Cl, K, Ca, Mn, Fe, Cu and Zn in NIST SRM 1577C ‘bovine liver’. LODs were calculated in ‘high dose’ mode. Only a single detector channel was used (XIA05). (XLSX)
Data
Calculation of ice layer thicknesses and Kα fluorescence absorbed. Ice layer thickness for which 10, 50 and 99% of the fluorescent photons of the elements P, S, Cl, K, Mn, Fe and Zn are absorbed (left main column). Percentage of absorbed Kα fluorescence for a specific element using the calculated ice thickness of the control and FRDA fibroblast usi...
Article
The potentially severe side effects of systemic corticosteroids and immunosuppressants used in Pemphigus vulgaris (PV) call for novel therapeutic approaches. In this context, pharmacological inhibition of major pathogenic signalling effectors represents a promising alternative. However, we have also shown that overinhibition of effectors required f...
Article
In the last few years many new cell death modalities have been described. To classify different types of cell death, the term ‘regulated cell death’ was introduced to discriminate it from ‘accidental cell death’. Regulated cell death involves the activation of genetically encoded molecular machinery that couples the presence of some signal to cell...
Article
Full-text available
Staphylococcus aureus is one of the most causative agents of mastitis and is associated with chronic udder infections. The persistency of the pathogen is believed to be the result of an insufficient triggering of local inflammatory signaling. In this study, the preclinical mastitis model was used, aiming to evaluate if lipopolysaccharide (LPS) or l...
Article
In acute kidney injury (AKI), the majority of dying tubular cells succumbs to an iron-dependent form of regulated necrosis, referred to as ferroptosis. Ferroptosis is essentially mediated by iron-catalyzed lipid peroxidation upon GPX4 dysfunction. Heme oxygenase 1 (HO-1) is a master regulator of intracellular free iron due to the conversion of heme...
Article
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating r...
Article
Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies...
Article
Several cell death assays have been developed based on a single biochemical parameter such as caspase activation or plasma membrane permeabilization. Our fluorescent apoptosis/necrosis (FAN) assay directly measures cell death and distinguishes between caspase-dependent apoptosis and caspase-independent necrosis of cells grown in any multiwell plate...
Article
Full-text available
Necroptosis was initially identified as a backup cell death program when apoptosis is blocked. However, it is now recognized as a cellular defense mechanism against infections and is presumed to be a detrimental factor in several pathologies driven by cell death. Necroptosis is a prototypic form of regulated necrosis that depends on activation of t...
Article
Ferroptosis is a non-apoptotic, iron-catalysed form of regulated necrosis that is critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute to liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition of ferroptosis with nanomolar activity a...
Article
Hair follicles are unique organs undergoing regular cycles of proliferation, differentiation, and apoptosis. The final step of apoptosis is, in general, mediated by executioner caspases comprising caspase-3, -6 and -7. Despite their commonly accepted apoptotic function, executioner caspases also participate in non-apoptotic processes. In the presen...
Article
Our current knowledge of the molecular mechanisms regulating the signaling pathways leading to cell survival, cell death, and inflammation has shed light on the tight mutual interplays between these processes. Moreover, the fact that both apoptosis and necrosis can be molecularly controlled has greatly increased our interest in the roles that these...
Article
Full-text available
Necrosis is not only a regulated process, it is an interconnected molecular network allowing different genetically encoded forms that are more or less immunogenic. Zhao et al. elegantly illustrate this concept, underscore the need for combination therapy to successfully interfere with regulated necrosis, and identify the role of regulated necrosis...