|Research fields||microglia, epigenetic regulation, multiple sclerose|
Title: Epigenetic regulation of neuroimmune tolerance in microglia
Project: Exposure to endotoxins, including bacterial cell wall components, can lead to a process called endotoxin tolerance (ET) of macrophages, characterized by a severely reduced inflammatory response to subsequent exposure to endotoxins. In human sepsis patients, ET is correlated with immune suppression and a high morbidity. In addition, patients surviving sepsis suffer from long-term cognitive impairment and functional disability, and their quality of life is severely reduced.
ET also occurs in microglia, the tissue macrophages in central nervous system (CNS) and this is associated with lasting detrimental effects on brain physiology. Perinatal exposure to LPS increases the risk of cognitive deficits in adults through long-term programming of neuroimmune responses. Underlying mechanisms of microglia ET tolerance and downstream cognitive and neurodegenerative effects are very poorly understood and are the focus of this study.
Grant supplier: NWO
Title: Unravelling the role of microglia in MS lesion progression from a single-cell perspective
Project: Glial cells fulfill multiple essential functions in the central nervous system (CNS). Especially a particular type of glial cell that represents the innate immune system in the CNS, microglia, are implicated in the origins and progression of MS. As a result they provide a potential therapeutic target. However, the exact contribution of microglia to disease progression is unclear. In MS patients a wide variety of microglia phenotypes are observed depending on their exact location in respect to lesions as well as the type of lesion. In order to determine if and how microglia are true therapeutic targets in MS, we aim to identify these differences between individual cells on a molecular level.
Grant supplier: Stichting MS research