Cell death is a crucial process in development, homeostasis and (patho)physiology. In normal conditions about 100 billion cell die mostly by apoptosis. However, many diseased conditions are associated with a deregulated balance in cell death. Too much or too sensitive cell death is associated with inflammatory and degenerative diseases, while too little or too insensitive cell death is associated with development of cancer and with therapeutic resistance. This implies that depending on the particular role of cell death in a given disease therapeutic strategies could be envisioned that either sensitize or desensitize cell death pathway. However, in order to do so, a profound knowledge is required not only of cell death pathway but also on the molecular mechanism that regulate these cell death pathways.
The VIB research unit of Peter Vandenabeele focuses on the molecular mechanisms of different cell death modalities (a.o. apoptosis, necroptosis, ferroptosis, immunogenic cell death) and cellular stress (ER stress), their regulation, their functional interactions and the role herein of caspases, RIPK and other signalling molecules. The unit is both interested in cell autonomous as well as intercellular aspects of cell death and cellular stress such as communication with the innate immune system. These processes are studied in an integrated way at the level of biochemistry, cell biology, development of conditional transgenic models and their role in various diseases models such as sepsis, skin inflammation and cancer, and intestinal inflammation and cancer. In order to identify novel targets in signalling of cell death modalities we developed a cellular screening platform in which we screen customized functional classes of libraries of sh/siRNAs (kinases, ubiquitylating enzymes, etc.), libraries of known clinical drugs and series of chemical compounds. The hits are then further examined in cellular systems and in experimental disease models for their potential to modulate cell death pathways or to influence disease models.
In the Bertrand subgroup, we focus on the elucidation of the molecular mechanisms regulating stress-induced cell survival/death, as well as innate immune/inflammatory responses, with a particular interest on the role of post-translational modifications, such as phosphorylation and ubiquitylation. This group is currently characterizing the cell death checkpoints (apoptotic and necroptotic) downstream of TNFR1, as well as identifying new regulators of death induced by endoplasmic reticulum (ER) stress.
In the Declercq subgroup we mainly focus on understanding the role of RIPK1, 3 and 4 and MLKL in inflammation and cancer in the skin. Therefore we make use of cellular models and in vivo mouse models. We are especially interested in investigating whether RIPK1, RIPK3 or MLKL can serve as therapeutic targets in skin inflammation. In addition, we investigate the functions of RIPK4 and secondary modifications controlling its activity.
In the Riquet subgroup, we are interested in biosensing and visualizing in a dynamic way complex formation, proteolysis and kinase activity during different forms of cellular stress and cell death. As a proof of concept we want to reveal the dynamics of RIPK1, RIPK3, and MLKL complex formation and activation in the initiation and execution phase of necroptosis in living cells and later in vivo. The dynamics and the visualization of these processes provide us with fundamental insights in the timing and subcellular localization of these processes in different cellular conditions, and might be very useful to think about therapeutic strategies and to validate the activity of novel and existing drugs.
Our fundamental research may have prognostic, diagnostic and therapeutic applications in cancer, inflammatory and neurodegenerative diseases, and skin pathologies.
Peter Vandenabeele’s work has been published in almost 300 articles and has been cited over 23000 times, with an h index of 81, according to Web of Science. Peter Vandenabeele is holder of the prestigious Methusalem grant from the Flemish Government.
Peter Vandenabeele has been chairman of the 11th and 18th Euroconference on Apoptosis organized in Ghent 2003 and 2010 by the European Cell Death Organization (ECDO).
He co-organized the first Symposium on ‘Mechanisms of Innate Immunity, Cell Death and Inflammation’ in 2014 in Ghent and will be chair of the bi-annual international TNF meeting in 2015 in Ghent in honour of Prof. Dr. Em. Walter Fiers.
> Watch the YouTube movies about apoptosis. - ©Peter Vandenabeele Lab - Vanden Berghe et al. CDD "2010"
> video on basic research on cell death by Peter Vandenabeele - ©VIB, 2014
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosisTakahashi N, Vereecke L, Bertrand M, Duprez L, Berger S, Divert T, Gonçalves A, Sze M, Gilbert B, Kourula S, Goossens V, Lefebvre S, Günther C, Becker C, Bertin J, Gough P, Declercq W, van Loo G, Vandenabeele PNATURE, 513, 95-9, 2014 MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphatesDondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, Hulpiau P, Weber K, Sehon C, Marquis R, Bertin J, Gough P, Savvides S, Martinou J, Bertrand M, Vandenabeele PCell Reports, 7, 971-81, 2014
31/03/2016 - Researchers in the group of Prof. Dr. Peter Vandenabeele (VIB/UGent) show that killed tumour cells can serve as a potent vaccine that stimulates the immune system to prevent the outgrowth of cancer cells.
15/12/2015 - Tom Vanden Berghe and colleagues from the Peter Vandenabeele Lab (VIB/UGent) have demonstrated how the side effects of genetic modification of mice can complicate the interpretation of biomedical research.
18/09/2015 - The team of Prof. Bertrand in the group of Prof. Vandenabeele, demonstrates that the IKK complex protects cells from death by inactivating RIPK1, thereby revealing an unexpected NF-kB-independent new role of the IKK complex.
28/08/2015 - The journal Cell Death & Disease gives an overview of their most cited papers. N°1 in Europe is one from the group of Peter Vandenabeele.
23/07/2015 - The research group of Prof Peter Vandenabeele (VIB/UGent) recently used tangible examples to demonstrate how the side effects of genetic modification of mice can complicate the interpretation of biomedical research.
01/07/2015 - Every five years, FWO Flanders selects five exceptional scientists in Flanders who play an international leading role in their field and have pushed the boundaries of their field.
29/12/2014 - Nozomi Takahashi and Peter Vandenabeele (Inflammation Research Center, UGent) have unraveled the crucial role of RIPK1 protein in keeping our gut epithelium intact.
24/09/2014 - Tom Vanden Berghe, from the research group of Peter Vandenabeele (VIB/UGent), in collaboration with Anje Cauwels (VIB/UGent), has discovered a potential (combination) therapy against sepsis.
03/09/2014 - Under normal conditions, RIPK1 is essential to protect gut epithelial cells from excessive cell death, and thereby ensures the barrier function of this organ from bacterial infiltration.
04/06/2014 - Researchers at VIB and Ghent University have unraveled the mechanism of necroptosis. This is a type of cell death that plays a crucial role in numerous diseases.
07/02/2014 - Scientists of VIB and UGent demonstrated that a potential novel treatment for sepsis may consist of the simultaneous neutralization of two harmful cytokines in the blood circulation, namely interleukin-1 and interleukin-18.
27/12/2011 - By blocking necroptosis, Peter Vandenabeele and his colleagues from from VIB-UGent were able to protect mice against the lethal condition sepsis, showing the central role of the molecule RIPK in this condition.
02/02/2009 - Foamix Ltd., a leading worldwide developer of topical foams for dermatology and gynecology has entered into an agreement with VIB for the development of a unique topical drug for the treatment of Psoriasis.
21/05/2007 - VIB researchers have demonstrated that the caspase-14 protein − whose function has been unknown up to now − not only plays a role in maintaining the balance of moisture in the skin but also offers protection against UVB rays.
PhD: Ghent University, Belgium, 1990
VIB Group leader since 1996