Research team
Expertise
After completing my biomedical education with specialization in clinical sciences at the University of Antwerp in 2017, I worked on and completed my PhD project at the University of Antwerp in the laboratory of Immunology and Allergology. After obtaining my PhD, I started as a postdoc researcher in the same laboratory. I conduct fundamental and translational research that mainly focuses on the activation and inhibition mechanisms of basophils and mast cells in anaphylaxis, clonal mast cell disorders and hypersensitivity reactions to drugs and Hymenoptera. In this research, mast cells are cultured from CD34+ progenitor cells isolated from peripheral blood or bone marrow. The analyzes of membrane characteristics, functional assays and cell culture are performed at the single cell level using flow cytometry. In addition, I have extensive experience with a human mast cell knock-down model using electroporation which I developed. Lastly, I started recently with performing genomics and transcriptomics in mast cells related diseases.
Mast cell-driven immediate drug hypersensitivity: an unprecedent transcriptomic exploration of the MRGPRX2 signaling cascade.
Abstract
Mast cell-driven immediate drug hypersensitivity reactions (IDHRs) are an important health issue with serious consequences due to diagnostic error. Unfortunately, diagnosis can be extremely challenging, mainly because mast cell activation leading to IDHRs can result from IgE-independent mechanisms that remain largely elusive. In this respect, the recently described MRGPRX2 pathway is an attractive mechanistic alternative. Although the clinical phenotype of MRGPRX2-mediated IDHRs and the classical sIgE-mediated IDHRs is comparable, there are several reasons why distinguishing between the two in an individual patient is relevant for personalized treatment. This is because sIgE- and MRGPRX2-mediated IDHRs have different characteristics in terms of recurrence risk, cross-reactivity patterns, facilitators (cofactors) and response to desensitization. The MRGPPRX2 activation and downstream signalling remain a complex conundrum with many knowledge gaps and uncertainties about potential risk factors. It has been demonstrated that MRGPRX2-mediated IDHRs occur in only a minority of individuals exposed to potential ligands. The reason for this individual susceptibility is currently unclear. In addition to receptor polymorphism, which is the focus of my FWO postdoctoral research project, gene variants in the downstream signalling pathways have also been postulated. However, there is currently a paucity of robust evidence to substantiate this assumption, mainly due to the lack of robust selection of study participants and the absence of a comprehensive genotyping strategy. Hence, this application, in which I seek to extend my FWO Senior Postdoc project and conduct a pilot study and to investigate the transcriptomic differences between resting and activated mast cells obtained from IDHR patients, to identify downstream signalling genes that contribute to MRGPRX2-mediated IDHRs.Researcher(s)
- Promoter: Elst Jessy
Research team(s)
Project type(s)
- Research Project
Mast cell driven immediate drug hypersensitivity: resolving the specific IgE versus MRGPRX2 conundrum.
Abstract
Immediate drug hypersensitivity (IDH) is an important health issue with serious consequences of diagnostic error. Unfortunately diagnosis can be extremely challenging, mainly as mast cell activation leading to IDH reactions can result from IgE-independent mechanisms that remain largely elusive. In this respect, the recently described MRGPRX2 pathway is an attractive mechanistic alternative. However, MRGPPRX2 activation and down-stream signalling remain a complex conundrum with many knowledge gaps and uncertainties about potential risk factors. Unfortunately, research in these domains is not straight forward, as it is mainly hampered by the absence of a technique to unambiguously document a MRGPRX2-mediated IDH reaction. Hence our project, aiming at optimizing our strategy to discriminate between sIgE- and MRGPRX2-mediated IDH reactions, an absolute prerequisite for further investigation of this putative endotype of IDH. In our proposal we will focus on the topography of skin mast cells, enhanced MRGPRX2 expression or functionality by mast cell and genomic or transcriptomic changes as possible explanations of MRGPRX2-mediated IDH reactions. Resolving the IgE vs. MRGPRX2 paradigm could result in more personalized medicine with identification of diagnostic and therapeutic targets for the individual patient.Researcher(s)
- Promoter: Sabato Vito
- Co-promoter: Ebo Didier
- Fellow: Elst Jessy
Research team(s)
Project type(s)
- Research Project
Diagnosing drug allergy: the T is the key
Abstract
Drug allergy is a significant health issue with a serious medical and financial burden of mis- and overdiagnosis. Currently applied tests differ for immediate and nonimmediate drug allergy and have variable sensitivity and specificity. Therefore, correct diagnosis remains difficult and frequently requires potentially dangerous and time-consuming challenge tests. Drug-specific T-cells play a central role in initiation and maintenance of both immediate and nonimmediate drug allergy and can be studied in the lymphocyte transformation test (LTT). However, technical difficulties have hindered entrance of the LTT in mainstream use. Our data indicate that flow-based intracellular trapping and staining of markers induced during activation (such as CD154 and cytokines) enables a rapid enumeration of rare drug-specific T-cells in the blood of patients with immediate and nonimmediate amoxicillin allergy. The ambition of this project is to validate our "one fits all" assay that meets the requirements of a safe, patient friendly, accessible, and performant test that could merits the status of a primary investigation in the diagnostic algorithms. Moreover, as the tests is cost effective, it could also become an attractive method for broader applications such as the delabelling of spurious allergies. This project will focus on allergy to amoxicillin.Researcher(s)
- Promoter: Sabato Vito
- Co-promoter: Elst Jessy
Research team(s)
Project type(s)
- Research Project
Mast cell driven immediate drug hypersensitivity: resolving the specific IgE versus MRGPRX2 conundrum
Abstract
Immediate drug hypersensitivity (IDH) is an important health issue with serious consequences of diagnostic error. Unfortunately diagnosis can be extremely challenging, mainly as mast cell activation leading to IDH reactions can result from IgE-independent mechanisms that remain largely elusive. In this respect, the recently described MRGPRX2 pathway is an attractive mechanistic alternative. However, MRGPPRX2 activation and down-stream signalling remain a complex conundrum with many knowledge gaps and uncertainties about potential risk factors. Unfortunately, research in these domains is not straight forward, as it is mainly hampered by the absence of a technique to unambiguously document a MRGPRX2-mediated IDH reaction. Hence our project, aiming at optimizing our strategy to discriminate between sIgE- and MRGPRX2-mediated IDH reactions, an absolute prerequisite for further investigation of this putative endotype of IDH. In our proposal we will focus on the topography of skin mast cells, enhanced MRGPRX2 expression or functionality by mast cell and genetics as possible explanations of MRGPRX2-mediated IDH reactions. Resolving the IgE vs. MRGPRX2 paradigm could result in more personalized medicine with identification of diagnostic and therapeutic targets for the individual patient.Researcher(s)
- Promoter: Sabato Vito
- Co-promoter: Ebo Didier
- Fellow: Elst Jessy
Research team(s)
Project type(s)
- Research Project