Projects
Role of linear ubiquitination in intestinal inflammation and disease Ghent University
Inflammatory bowel diseases (IBD) are chronic conditions characterized by inflammation of the gastrointestinal tract. IBD patients suffer from increased intestinal epithelial cell (IEC) apoptosis and exhibit a hyperactivated NF-kB pathway leading to immune system activation and proinflammatory cytokine production. Recent studies have indicated that linear ubiquitination is a key regulatory mechanism of NF-κB signalling and cell death. ...
Capturing the ubiquitination and protein interaction landscape of the central regulator of nodulation TOO MUCH LOVE in soybean Ghent University
Soybean is one of the most important plant-based protein sources for food and feed. This legume acts as a natural nitrogen fertilizer by establishing a symbiotic relationship with nitrogen-fixing rhizobia in a process called nodulation. As nodulation is energetically costly, the number of formed nodules is tightly regulated through a systemic pathway called autoregulation of nodulation (AON). The key component acting at the final stages of ...
Alterations in RAS interactome triggered by ubiquitination KU Leuven
Ubiquitination is one of the most prominent post-translational modifications in all eukaryotic systems. For decades, ubiquitination was mainly considered as a tag directing substrate proteins to proteasomal degradation. However, it has become more and more clear that ubiquitination can alter functioning of the target protein in many ways depending on the type of ubiquitin conjugation and target site of ubiquitination. In this project, we will ...
Role of ubiquitination in phase transitions in Amyotrophic Lateral Sclerosis (ALS) Vrije Universiteit Brussel
Investigating the effects of regulatory phosphorylation and linear ubiquitination on Pyrin-mediated auto-inflammatory disorders. Ghent University
Enhanced inflammasome signaling due to Pyrin mutations underlie auto-inflammation in Familial Mediterranean Fever (FMF). We obtained evidence that also Otulin-related auto-inflammatory syndrome (ORAS) involves enhanced Pyrin signaling. In this project, we will investigate the mechanisms by which Pyrin signaling is regulated by phosphorylation and linear ubiquitination, and how this modulates Pyrin-mediated auto-inflammation in FMF and ORAS ...
Elucidation of a link between RCBTB1-associated inherited retinal dystrophy and ubiquitination by in vitro and in vivo studies Ghent University
Mendelian eye disorders such as inherited retinal dystrophies (iRDs) are a major cause of blindness worldwide. Last year, our team identified RCBTB1 as a novel gene for autosomal recessive iRD, with extra-ocular manifestations in a few patients. RCBTB1 was recently suggested to be involved in ubiquitination, however, little is known about its function in this pathway.
Based on preliminary data, we hypothesize that biallelic RCBTB1 ...
The role of RAS ubiquitination in cancer development and progression. KU Leuven
The RAS GTPases are among the most commonly mutated oncoproteins in human cancers. We and others recently demonstrated a crucial role of reversible ubiquitination in regulation of the RAS GTPases. The primary objective of the proposed study is to understand the contribution of RAS ubiquitination in RAS-mediated tumorigenesis. Using a quantitative proteomic analysis of the ubiquitinated RAS interactome, we will assess how ubiquitination ...
Role of NRas ubiquitination in control of melanoma development and progression. KU Leuven
Melanoma is one of the most aggressive skin cancers. The 15–20% of all melanomas harbors activating NRas mutations. At present, little progress has been made in developing targeted therapy strategies for NRas mutant melanoma, thus a better understanding of the Ras pathway is an urgent need for establishing new treatment strategies. We and others have recently demonstrated that ubiquitination of the Ras family members dramatically affects ...
Global analysis of the effect of dopamine D4 receptor ubiquitination on receptor signaling Ghent University
Receptors are proteins in cells important for signaling; endogenous molecules released by one cell
influence the other cell by activating receptors. Many receptors are located at the outside of the cells
(ie in the cell membrane). The largest group of membrane receptors consists of the G protein-coupled
receptors (GPCRs). They are called GPCRs because upon stimulation, they activate another type of
protein (G protein) ...