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Overview
Our laboratory applies functional genomics combined with high-resolution confocal microscopy, to resolve the underlying mechanisms of mast cell exocytosis. The latter is the primary process by which mast cells release inflammatory mediators that are pre-formed and stored in secretory granules, thereby exerting both their physiological functions in innate and adaptive immunity and their pathological functions during allergy, chronic inflammation linked with cancer, autoimmune diseases and neurogenic inflammation.
Functional genomics and phenotypic traits of mast cell exocytosis in allergy
We have recently developed an innovative strategy that is based on the co-expression of a gene of interest and a fluorescent reporter for exocytosis. In combination with high-resolution microscopy, this method allows us to perform functional genomics and phenotypic analyses of mast cell exocytosis. Applying this method to screen Rab GTPases, that are master regulators of cellular trafficking, we identified 30 Rabs as novel regulators of mast cell degranulation. The identification of the Rab network that controls mast cell exocytosis is instrumental for deciphering the underlying molecular mechanisms of exocytosis. Using this method, we aim to decipher fundamental questions in mast cell biology:
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How are mast cell secretory granules formed?
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How are mast cell secretory granules size and number regulated?
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How do the secretory granules move towards the plasma membrane in order to release their content?
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Why does a fraction of secretory granules always move in the opposite direction?
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Why do mast cells vigorously release their secretory granule content (anaphylactic degranulation), in response to some triggers (for example IgE/allergen), but release only a subset of mediators in response to others (for example during chronic or neurogenic inflammation)?
Mast cells in the tumor microenvironment
For a long time mast cells have been shown to infiltrate the tumor microenvironment. However, in some cancer types, the increase in mast cells number surrounding the tumor indicates a poor prognosis, while in other cancer types, mast cell contributes to fighting cancer. We aim to decipher the mechanism of cancer-mast cell cross-talk in various cancer types trough examining the properties of cell-cell interactions as well as exosome-mediated transfer between mast cells and cancer cells.
Mast cells in ageing
Immune cells in the brain are crucial for proper synaptic physiology. We have recently begun researching the effect of ageing on brain mast cells and their cross-talk with microglia in Alzheimer's disease in an attempt to elucidate:
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What is the role of brain mast cells and how do they contribute to the progression of neurodegenerative diseases?
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How does aging affect mast cell function?
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